Complications in Surgery 2nd Ed

Com p lications
in Su rgery
S ECON D EDI TI ON
EDI TORS
Michael W. Mulholland, MD, PhD

Frederick A. Coller Distinguished Professor of Surgery and Chairman; Surgeon-in-Chief,
Department of Surgery, University of Michigan, Ann Arbor, Michigan
Gerard M. Doherty, MD
N.W. Thompson Professor of Surgery; Vice-Chair, Department of Surgery,
University of Michigan, Ann Arbor, Michigan
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Com plications in su rgery / ed itors, Michael W. Mu lholland , Gerard M.
Doherty. – 2nd ed .
p . ; cm .
Includ es bibliograp hical references and ind ex.
ISBN 978-1-60547-530-1 (hard back : alk. p ap er)
1. Su rgery–Com plications. I. Mu lholland , Michael W. II. Doherty,
Gerard M.
[DN LM: 1. Intraoperative Com p lications. 2. Postop erative
Com plications. 3. Surgical Proced u res, Operative–ad verse effects. WO
181]
RD98.C63 2011
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2011004679
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To our wives, Patricia and Faith
CONTRIBUTORS
Sanjeev Aggarwal, MD Andrew C. Chang, MD Matthew J . Eagleton, MD

Director, Mechanical Circu latory Assistant Professor Assistant Professor
Su p p ort Departm ent of Su rgery Dep artm ent of Vascu lar Su rgery
Associate Director, Card iac University of Michigan Cleveland Clinic Lerner College of
Transp lantation Ann Arbor, Michigan Med icine of Case Western Reserve
Mid America H eart Institu te University
Craig M. Coopersmith, MD, FCCM, FACS
Saint Lu ke’s H osp ital of Kansas City Staff, Vascu lar Su rgery
Assistant Professor
Kansas City, Missou ri The Cleveland Clinic Fou nd ation
Departm ents of Su rgery and
Cleveland , Ohio
Gorav Ailawadi, MD Anesthesiology
Assistant Professor Washington University School of J onathan L. Eliason, MD
Dep artm ent of Su rgery Med icine Assistant Professor
University of Virginia Attend ing Physician, Barnes-Jew ish Dep artm ent of Su rgery
Charlottesville, Virginia H osp ital University of Michigan
Saint Lou is, Missou ri Ann Arbor, Michigan
Ahmad Azari, MD
Clinical Instru ctor Traves D. Crabtree Michael J . Englesbe, MD
Dep artm ent of Su rgery and OB-GYN Assistant Professor Assistant Professor of Surgery
University of Michigan Departm ent of Su rgery Dep artm ent of Su rgery
Ann Arbor, Michigan Washington University University of Michigan
Barnes Jew ish H ospital Ann Arbor, Michigan
Richard J . Battafarano, MD, PhD
St. Lou is, Missouri
Assistant Professor of Su rgery J onathan F. Finks, MD
Chief, Division of Thoracic Su rgery Niraj M. Desai, MD Assistant Professor
Washington University School of Departm ent of Su rgery Dep artm ent of Su rgery
Med icine Johns H opkins University University of Michigan
Saint Lou is, Missou ri Balitim ore, Maryland Ann Arbor, Michigan
J ohn D. Birkmeyer, MD J ustin B. Dimick, MD, PhD Emily Finlayson, MD
George D. Zuidema Professor of Surgery Assistant Professor Assistant Professor
Dep artm ent of Su rgery Departm ent of Su rgery Division of General Su rgery
University of Michigan University of Michigan University of California, San Francisco
Director of Bariatric Su rgery Ann Arbor, Michigan San Francisco, California
University H osp ital
Gerard M. Doherty, MD Michael G. Franz, MD
Ann Arbor, Michigan
N .W. Thom pson Professor of Su rgery Associate Professor of Su rgery
Imad F. Btaiche, PharmD, BCNSP Vice-Chair Dep artm ent of Su rgery
Clinical Associate Professor Departm ent of Su rgery University of Michigan
Dep artm ent of Clinical, Social and University of Michigan Ann Arbor, Michigan
Ad ministrative Sciences Ann Arbor, Michigan
Bradley D. Freeman, MD, FACS
University of Michigan College of
J ames M. Donahue, MD Professor
Pharm acy
Assistant Professor of Surgery Dep artm ent of Su rgery
Program Director, Critical Care
General Thoracic Su rgery Washington University School of
Resid ency
Greenebau m Cancer Center Med icine
Clinical Pharm acist, Su rgery and
University of Maryland Attend ing Su rgeon
N u trition Su p port
Maryland Barnes Jew ish H osp ital
University of Michigan H osp itals and
St. Louis, Missouri
H ealth Centers J essica S. Donington, MD
Ann Arbor, Michigan Assistant Professor Kevin Fung, BA, MD, FRCS(C)
Departm ent of Card iothoracic Su rgery Assistant Professor
Richard E. Burney, MD
N YU School of Med icine Dep artm ent of Otolaryngology
Professor
N ew York, N ew York Dep artm ent of Oncology
Dep artm ent of Su rgery
Director of the Vocal H ealth Clinic
University of Michigan Kim A. Eagle, MD
Director of Und ergrad u ate Affairs
Ann Arbor, Michigan Albion Walter H ew itt Professor of
Royal College of Physicians and
Internal Med icine
Darrell A. Campbell J r., MD Su rgeons of Canad a
Departm ent of Internal
H . King Ransom Professor of Su rgery American Board of Otolaryngology
Med icine/ Card iovascu lar Med icine
Chief of Staff Lond on H ealth Sciences Centre
Director, Card iovascu lar Center
Office of Clinical Affairs Westm inster Cam pu s, Lond on
University of Michigan
University of Michigan Ontario Canad a
Ann Arbor, Michigan
Ann Arbor, Michigan
v
vi Contributors
Samir K. Gadepalli, MD, MBA Ronald B. Hirschl, MD Christine L. Lau, MD

Fellow, Pediatric Surgery Arnold G. Coran Professor of Associate Professor
University of Michigan Ped iatric Su rgery University of Virginia H ealth System
C.S. Mott Child ren’s H ospital University of Michigan Division of Thoracic and
Ann Arbor, Michigan Su rgeon-in-Chief Card iovascular Su rgery
C.S. Mott Child ren’s H ospital Charlottesville, Virginia
Paul G. Gauger, MD
Ann Arbor, Michigan
William J. Fry Professor of Su rgery J ennifer S. Lawton, MD
Dep artm ents of Su rgery and Med ical Norman D. Hogikyan, MD, FACS Associate Professor
Ed u cation Professor, Departm ent of Dep artm ent of Su rgery
University of Michigan Otolaryngology—H ead and Division of Card iovascu lar Surgery
Ann Arbor, Michigan N eck Su rgery Washington University
Chief, Division of Laryngology, Card iothoracic Su rgeon
J ames D. Geiger, MD
Rhinology and General Barnes Jew ish H ospital
Professor of Su rgery
Otolaryngology St. Louis, Missouri
University of Michigan Cortney Youens Lee, MD
Ann Arbor, Michigan
Ann Arbor, Michigan Su rgery
Mark D. Iannettoni, MD End ocrine Su rgery Fellow
Alicia Growney, MD
Johann L. Ehrenhaft Professor and Dep artm ent of Su rgery
Clinical Instru ctor
Chairm an Texas A&M University/ Scott and
Departm ent of Card iothoracic Su rgery White Clinic
University of Iow a H ospitals and Temp le, Texas
Ann Arbor, Michigan
Clinics
Spencer J . Melby, MD
Richard Van Harrison, PhD Iow a City, Illinois
Fellow, Division of Card iothoracic
Professor
Paul Kanzanjian, MD Su rgery
Dep artm ent of Med ical Ed ucation
Assistant Professor Washington University in St. Lou is/
Departm ent of Anesthesiology Barnes Jew ish H osp ital
Ann Arbor, Michigan
University of Michigan St. Louis, Missouri
Linnea S. Hauge, PhD Ann Arbor, Michigan
Robert M. Merion, MD
Assistant Professor and
Dixon B. Kaufman, MD Professor of Su rgery
Dep artm ents of Su rgery and Med ical
Professor Dep artm ent of Su rgery
Ed u cation
Departm ent of Su rgery University of Michigan
Feinberg School of Med icine Ann Arbor, Michigan
Ann Arbor, Michigan
N orthw estern University
Bryan F. Meyers, MD
Awori Hayanga, MD Chicago, Illinois
William son Professor of Su rgery
Resid ent in Thoracic Surgery
Christina L. Klein, MD Washington University School of
University of Washington
Assistant Professor Med icine
Seattle, Washington
Departm ent of Med icine Saint Lou is, Missou ri
Mark J . Hemmila, MD Washington University in St. Lou is
Rebecca M. Minter, MD
Associate Professor School of Med icine
Associate Professor Su rgery
Dep artm ent of Su rgery St. Lou is, Missouri
Assistant Professor of Med ical
Mary E. Klingensmith, MD Ed u cation
Ann Arbor, Michigan
Professor of Su rgery Dep artm ents of Surgery and Med ical
Peter K. Henke, MD Washington University School of Ed u cation
Associate Professor Med icine University of Michigan
Dep artm ent of Su rgery St. Lou is, Missouri Ann Arbor, Michigan
J ames A. Knol, MD Eiichi Miyasaka, MD
Ann Arbor, Michigan
Associate Professor Research Fellow
Sara A. Hennessy, MD Departm ent of Su rgery Dep artm ent of Su rgery
Resid ent in Su rgery University of Michigan University of Michigan
Dep artm ent of Su rgery Ann Arbor, Michigan Ann Arbor, Michigan
University of Virginia
Terry C. Lairmore, MD J effrey F. Moley, MD
Charlottesville, Virginia
Professor of Su rgery Professor, Su rgery
Director, Division of Su rgical Oncology Division of General Surgery
Texas A&M University H ealth Science Washington University School of
Center, College of Med icine Med icine
Scott & White H ospital Saint Lou is, Missou ri
Tem p le, Texas
Contributors vii
Marc R. Moon, MD J ohn E. Rectenwald, MD Randall S. Sung, MD

Joseph C. Bancroft Professor of Surgery Professor of Su rgery Associate Professor
Dep artm ent of Su rgery Section of Vascu lar Surgery Dep artm ent of Su rgery
Washington University School of University of Michigan University of Michigan
Med icine Ann Arbor, Michigan Ann Arbor, Michigan
Saint Lou is, Missou ri Alvin H. Schmaier, MD Daniel H. Teitelbaum, MD
Arden M. Morris, MD Robert W. Kellerm eyer Professor of Professor of Su rgery
Associate Professor H em atology and Oncology Dep artm ent of Su rgery
Dep artm ent of Su rgery Dep artm ent of Med icine University of Michigan
University of Michigan Case Western Reserve University Ann Arbor, Michigan
Ann Arbor, Michigan Director of the Ireland Cancer Center
Laboratory and Hemophilia Program Gilbert R. Upchurch J r., MD
Debabrata Mukherjee, MD, FACC Professor of Su rgery
Dep artm ent of Med icine
Chief, Card iovascu lar Med icine Dep artm ent of Su rgery
University Hospital Case Medical Center
Professor of Internal Med icine University of Virginia
Cleveland , Ohio
Vice Chairm an, Dep artm ent of Internal Charlottesville, VA
Med icine Diane M. Simeone, MD
Texas Tech University Lazar J. Greenfield Professor of Wendy Wahl, MD
El Paso, Texas Su rgery and Molecular & Integrative Professor
Physiology Dep artm ent of Su rgery
Michael W. Mulholland, MD, PhD University of Michigan
Fred erick A. Coller Distingu ished Ann Arbor, Michigan
Professor
Ann Arbor, Michigan Thomas W. Wakefield, MD
Su rgeon-in-Chief
Chairm an, Dep artm ent of Surgery Michael A. Smith, MD S. Martin Lind enau er Professor of
University of Michigan Assistant Professor Su rgery
Ann Arbor, Michigan Card iothoracic Su rgery Dep artm ent of Su rgery
Keck School of Med icine University of Michigan
Lisa A. Newman, MD, MPH, FAC Ann Arbor, Michigan
University of Sou thern California
Professor of Su rgery and Director
Los Angeles, California Stewart Wang, MD, PhD
Ann Arbor, Michigan Christopher J . Sonnenday, MD, MHS Professor of Su rgery
Assistant Professor Associate Chairman of Su rgery
Francis D. Pagani, MD, PhD University of Michigan
Otto Gago, MD, Professor in Card iac Dep artm ent of Su rgery
University of Michigan Ann Arbor, Michigan
Su rgery
Director, H eart Transp lant Program Ann Arbor, Michigan Christina H. Wei, MD
Director, Center for Circulatory Support Robert E. Southard, MD General Su rgeon
Dep artm ent of Su rgery Assistant Professor San Francisco, California
University of Michigan Division of General Surgery Theordore H. Welling, MD
Ann Arbor, Michigan Section of Acu te and Critical Care Assistant Professor
Pauline K. Park, MD, FACS, FCCM Su rgery Dep artm ent of Su rgery
Associate Professor, Su rgery Washington University School of University of Michigan
Co-Director, Su rgical Intensive Care Med icine Ann Arbor, Michigan
Unit Saint Lou is, Missouri
Alliric I. Willis, MD
Ann Arbor, Michigan Sunita D. Srivastava, MD Assistant Professor of Surgery
Harvey I. Pass, MD Assistant Professor University of Pennsylvania School of
Professor, Dep artm ent of Su rgery and Section of Vascu lar Surgery, Med icine
Card iothoracic Su rgery Dep artm ent of Su rgery Philad elp hia
Vice-Chairm an for Research and Cleveland Clinic Lerner College of
Med icine of Case Western Reserve Sandra L. Wong, MD, MS
Division Chief, Thoracic Su rgery
University Assistant Professor
Dep artm ent of Card iothoracic Su rgery
Staff, Dep artm ent of Vascu lar Su rgery Dep artm ent of Su rgery
N YU Langone Med ical Center
The Cleveland Clinic Found ation University of Michigan
N ew York, N ew York
Cleveland , Ohio Ann Arbor, Michigan
Shawn J . Pelletier, MD
Assistant Professor J ames C. Stanley, MD
Dep artm ent of Su rgery Professor of Su rgery
University of Michigan Section of Vascu lar Surgery
Ann Arbor, Michigan Co-d irector, Card iovascu lar Center
Ann Arbor, Michigan
PREFACE
Su rgical therap y is inherently risky. All surgeons seek to m any instances, the setting of care is as im p ortant in clini-
balance an op eration’s potential benefit and risk w ith the cal ou tcom es as the ind ivid u al su rgeon.
d isease being treated . The best su rgeons d isplay a com bi- Complications in Surgery is organized to cover both the
nation of know led ge, technical skill, and clinical ju d gm ent. broad concepts of surgical care and the complications relevant
Know led ge begins w ith a thou ghtfu l ap p raisal of the m ed - to operations on specific organs. Surgical epidemiology, oper-
ical literatu re. Op erative technical ability d evelops from an ative technique, and disease pathophysiology are each essen-
und erstand ing of the process of su rgery w ith com p rehen- tial in contemporary surgical practice; each is emphasized in
sion of both the op eration’s objectives and the step s need ed this new textbook. In selecting contributors to Complications
to m eet them . Clinical jud gm ent m ay be d evelop ed in Surgery, the editors sought surgeons who had significant
ind ivid u ally from experience, but it is also acqu ired from clinical experience with the diseases and the operations
the d istilled exp erience of others. Su rgical ju d gm ent and described. In addition, the authors chosen are active contribu-
und erstand ing crucially d epend on a d etailed read ing of tors to new clinical knowledge and to the contemporary prac-
the su rgical literatu re and the exp ertise of others. tice of surgery. The editors believe that the second edition of
In recent years, it has becom e clear that su rgical resu lts Complications in Surgery makes a truly unique contribution to
d epend not only on ind ivid ual technical facility and ju d g- the surgical literature—unique in its concept, focus, and
ment but also on the system in w hich a su rgeon treats breadth. We hope that our readers will find that the book
patients. Institu tional p aram eters, the organization of clini- combines unique perspectives and information on modern
cal care, and team w ork play key roles in assu ring that surgical practice. Our ultimate goal, of course, is to positively
patients receive care that is both safe and efficaciou s. In affect the lives of the patients we are honored to serve.
ix
ACKNOWLEDGMENTS
We are very gratefu l to th e ou tstand ing grou p of contrib- d etailed d raw ings clarify and ad d d etail to the con tribu -
u tors w ho w e believe are u nchallenged in their u nd er- tors’ text. We have enjoyed w ond erfu l su p p ort for Jenny
stand ing and exp erience in these areas of su rgery. We Koleth and Brian Brow n at Lip p incott, William s &
ap p reciate th eir p reciou s tim e and effort on th is p roject. Wilkins w ho gently gu id ed this p rocess. It has been a
We are p rivileged to h ave w orked w ith H olly Fisch er, p leasu re for u s to w ork w ith su ch a d ed icated grou p of
M.F.A., w ho d id the original d raw ings. H er carefu lly ind ivid u als.
xi
CONTENTS
Contributors v 20. Abnorm alities in Coagu lation . . . . . . . . . . . . . . . . 200

Preface ix Alvin H. Schmaier
Acknowledgments xi 21. Com p lications of N u tritional Su p p ort . . . . . . . . . 210
Imad F. Btaiche, Eiichi Miyasaka, and Daniel H. Teitelbaum
P ART I : 22. Com p lications of Im m u nosu p p ression . . . . . . . . . 227
INSTITUTIONAL ISSUES Niraj M. Desai and Christina L. Klein
1. Su rgical Com plications . . . . . . . . . . . . . . . . . . . . . . . . 3 P ART I I I :

Michael W. Mulholland and Gerard Doherty
COMPLICATIONS OF THORACIC SURGERY
2. Learning from Unanticipated
Ou tcom es and Error . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 23. Com p lications of Intu bation, Tracheotom y,
Linnea S. Hauge and Tracheal Su rgery . . . . . . . . . . . . . . . . . . . . . . . . 241
3. Su rgical Training: Present and Futu re . . . . . . . . . . . 13 Kevin Fung and Norman D. Hogikyan
Rebecca M. Minter and Paul G. Gauger 24. Com p lications of Esop hageal Su rgery . . . . . . . . . 257
4. Continuing Education for Practicing Surgeons . . . . 22 Andrew C. Chang and Mark D. Iannettoni
Richard E. Burney and R. Van Harrison 25. Com p lications of Pu lm onary and
5. Su rgical Cred entials . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Chest Wall Su rgery . . . . . . . . . . . . . . . . . . . . . . . . . . 276
Mary E. Klingensmith Christina H. Wei and Jessica S. Donington
6. Und erstand ing Variation in 26. Com p lications of Extracorp oreal Circu lation . . . . 290
Su rgical Ou tcom es . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Jennifer S. Lawton
Justin B. Dimick and John D. Birkmeyer 27. Com p lications of Su rgical Coronary
7. Strategies for Red u cing Variation in Revascu larization . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
Su rgical Ou tcom es . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 Spencer J. Melby, Traves D. Crabtree, and Marc R. Moon
John D. Birkmeyer and Justin B. Dimick 28. Com p lications in Valvu lar
8. Bu ild ing Su ccessfu l Quality Im provem ent Card iac Su rgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310
Collaboratives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Gorav Ailawadi
Michael J. Englesbe 29. Com p lications of Thoracoscop y . . . . . . . . . . . . . . . 320
9. Patient Safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 James M. Donahue, Michael A. Smith, and Richard J. Battafarano
Darrell A. Campbell
P A R T I V:
P ART I I : COMPLICATIONS OF VASCULAR SURGERY
MANAGEMENT OF SURGICAL COMPLICATIONS
30. Com p lications of Arterial Su rgery . . . . . . . . . . . . . 331
10. Assessm ent of Perioperative Card iac Risk . . . . . . . 67 Gilbert R. Upchurch Jr., Jonathan L. Eliason, John E. Rectenwald,
Debabrata Mukherjee and Kim A. Eagle and James C. Stanley
11. Assessm ent of N oncard iac 31. Com p lications of Venou s Disease
Periop erative Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 and Therap y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349
Pauline K. Park Thomas W. Wakefield and Peter K. Henke
12. Anesthesia Com plications . . . . . . . . . . . . . . . . . . . . . 91 32. Com p lications of End ovascu lar Therap y . . . . . . . 367
Paul E. Kazanjian Matthew J. Eagleton and Sunita D. Srivastava
13. Com p lications of Wou nd H ealing . . . . . . . . . . . . . 128
Michael G. Franz P A R T V:
14. Su rgical Site Infections. . . . . . . . . . . . . . . . . . . . . . . 140 COMPLICATIONS OF GASTROINTESTINAL SURGERY
Gerard M. Doherty
15. Sep tic Shock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 33. Com p lications of Gastric Su rgery . . . . . . . . . . . . . 393
Awori Hayanga and Stewart Wang Michael W. Mulholland
16. H yp ovolem ic Shock . . . . . . . . . . . . . . . . . . . . . . . . . 161 34. Com p lications of H ep atic Su rgery . . . . . . . . . . . . . 415
Wendy L. Wahl Theodore H. Welling and James A. Knol
17. Flu id and Electrolyte Abnorm alities . . . . . . . . . . . 168 35. Com p lications of Biliary Su rgery . . . . . . . . . . . . . . 429
Bradley D. Freeman Christopher J. Sonnenday
18. Acu te Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . 174 36. Com p lications of Pancreatic Su rgery . . . . . . . . . . . 450
Robert E. Southard and Craig M. Coopersmith Diane M. Simeone
19. Pu lm onary Com plications . . . . . . . . . . . . . . . . . . . 181 37. Com p lications of Intestinal Su rgery:
Mark R. Hemmila Small Bow el . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 464
Arden M. Morris
xiii
xiv Contents
38. Com p lications of Append ectom y and P A R T VI I :

Colon and Rectal Su rgery . . . . . . . . . . . . . . . . . . . . 483 COMPLICATIONS OF TRANSPLANTATION
Emily Finlayson
39. Com p lications of Abd om inal Wall and 47. Com p lications of Renal Transp lantation . . . . . . . . 613
H ernia Op erations . . . . . . . . . . . . . . . . . . . . . . . . . . 500 Randall Sung and Robert Merion
Michael G. Franz 48. Com p lications of Liver Transp lantation . . . . . . . . 627
40. Com p lications of Lap aroscopic Su rgery . . . . . . . . 522 Shawn J. Pelletier
Jonathan F. Finks 49. Com p lications of Pancreatic Transp lantation . . . . 640
Dixon B. Kaufman
P A R T VI : 50. Com p lications of Pu lm onary
COMPLICATIONS OF ENDOCRINE AND Transp lantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 656
ONCOLOGIC SURGERY Sara A. Hennessy, Bryan F. Meyers, and Christine L. Lau
51. Com p lications Follow ing
41. Com p lications of Ad renal Surgery . . . . . . . . . . . . 535 H eart Transp lantation . . . . . . . . . . . . . . . . . . . . . . . 674
Paul G. Gauger Sanjeev Aggarwal and Francis D. Pagani
42. Com p lications of Thyroid and
Parathyroid Su rgery . . . . . . . . . . . . . . . . . . . . . . . . . 550 P A R T VI I I :
Gerard Doherty COMPLICATIONS OF PEDIATRIC SURGERY
43. Com p lications in End ocrine
Pancreatic Su rgery . . . . . . . . . . . . . . . . . . . . . . . . . . 567 52. Su rgical Com p lications in N ew borns . . . . . . . . . . 701
Cortney Youens Lee and Terry C. Lairmore Samir Gadepalli and Ronald B. Hirschl
44. Com p lications in Breast Surgery . . . . . . . . . . . . . . 576 53. Su rgical Com p lications in Child ren . . . . . . . . . . . . 746
Alicia Growney, Ahmad Azari, and Lisa A. Newman James D. Geiger
45. Com p lications of Soft-Tissu e Tu m or Surgery . . . . 594
Sandra L. Wong Index 769
46. Com p lications of Lym phad enectomy . . . . . . . . . . 602
Alliric I. Willis and Jeffrey F. Moley
PART
Institutional Issues
CHAPTER
Surgical Complications
Michael W. Mulholland and Gerard Doherty
A su rgical com p lication is any u nd esirable, unintend ed , ap p roxim ately 14% of the cou ntry’s gross d om estic prod -
and d irect resu lt of an op eration affecting the patient that u ct (GDP), $1.1 trillion, w as sp ent on health services. By
w ou ld not have occu rred had the op eration gone as w ell as 2007, this figu re increased to $2.2 trillion, am ou nting to
cou ld reasonably be hoped (1). 16.2% of GDP or $7421 p er p erson, and health care reform s
Surgical care has alw ays focused on balancing risk and becam e a m ajor factor in Am erican electoral politics (3,4).
benefit. In trad itional su rgical teaching, risk is represented The Agency for H ealthcare Research and Qu ality has id en-
by operative comp lications, w hile benefit is equ ated w ith tified the top p riority cond itions: cancer, d iabetes m ellitus,
cure rates or palliation of symptoms. In the second half of em p hysem a, hu m an im m u nod eficiency viru s (H IV) infec-
the past century, surgical attention w as d irected to avoid ing tion, hyp ertension, ischem ic heart d isease, stroke, and
complications by d eveloping meticulous operative tech- gallstones. Many of these cond itions are highly relevant
niques and through early d etection of p ostoperative p rob- to contem p orary su rgical p ractice. In treating p atients
lem s w ith rap id efforts to m inim ize u nd esirable events. w ith these cond itions, the 21st centu ry health care system
While su rgical complications are often obviou s and clearly m u st ad ap t and focu s increasingly u p on p rovision of care
tied to the act of surgical intervention, issues of risk have that is
trad itionally been regard ed as a private matter ad d ressed
betw een an ind ivid ual su rgeon and a single p atient. safe,
This trad itional view of su rgical risk and benefit is no effective,
longer ad equ ate. Risk, still, properly begins w ith an assess- p atient-centered ,
ment of intraoperative problem s and p ostoperative events. tim ely,
Su rgical risk in contem p orary p ractice also inclu d es con- efficient, and
sid eration of balancing com plem entary, som etim es com - equ itable (5).
peting, techniqu es and achieving resu lts that op tim ize
physical, occu p ational, and societal goals. Mod ern su r- Patient safety has becom e a m ajor issue for Am erican
geons m ust appreciate the approp riate sequence and com - p atients and has p rom p ted increasing efforts to prom ote a
bination of op erative and nonoperative therap y. Ju d iciou s cu ltu re of hosp ital safety. As d etailed in Chapter 9 of this
utilization of resources is now a consid eration. Patient second ed ition, safety m eans “freed om from harm ”; in the
engagem ent and satisfaction, in ad d ition to physical heal- context of p atient care safety m eans freed om from harm
ing, are requ ired . associated w ith any m ed ical action or treatm ent. Quality is
The relationship of an ind ivid u al su rgeon w ith an ind i- a m ore global term referring to a “d egree of excellence.” It
vid u al p atient, still central to su rgical care, has becom e is theoretically possible for a hospital to be safe but offer
overlaid w ith increased scru tiny and w ith ad d itional socie- average or p oor qu ality. H ow ever, it is not p ossible for a
tal exp ectations. Stand ard s of exp ected outcom es for hospital to be of high quality and unsafe.
groups of patients require evid ence-based practice and N ew know led ge related to the p ractice of surgery has
have m ad e both seniority and ind ivid u al experience less increased exp onentially d u ring the p ast d ecad e. Su rgical
im p ortant. Su rgical care m u st be provid ed w ithin financial stu d ies are also increasingly sop histicated , requ iring of the
constraints. Societal interest in surgical ou tcomes is read er know led ge of p atient selection, statistical analysis,
expressed in the now -fam iliar Institu te of Med icine report, and m olecu lar biology. The nu m ber of d ru gs, surgical
“To Err Is H u m an,” w hich d etailed “unnecessary” d eaths d evices, and technological su p p ort system s has expand ed
resu lting from su rgical com p lications (2). as w ell. In this context, it is not p ossible for any one clini-
Investm ent in the health care sector by the Am erican cian to synthesize all of the inform ation necessary for effec-
society is enorm ous and continues to grow. In 1997, tive, evidence-based practice. No surgeon can read , organize,
and recall the cu rrent volu m es of clinically im p ortant infor-
m ation (5). Chap ter 6, “Und erstand ing variation in su rgical
Michael W. Mulholland, Gerard M. Doherty: University ou tcom es,” is d esigned to p rovid e a fram ew ork for this
of Michigan, Ann Arbor, MI 48109. new field of inqu iry.
3
4 Part I • Institutional Issues
The revolu tion in inform ation technology has the The ethics of surgical complications can be d escribed in
potential to greatly accelerate changes in su rgical care, to the framew ork of the “Four Principles” approach to medical
m ake that care both m ore effective and safer. Red uction in ethics, including respect for patient autonomy, beneficence,
su rgical com p lications w ill requ ire effective u se of the nonmaleficence and justice (7,8). The stress of responsibility
available scientific d atabase. Evid ence m u st be instantly for patient outcomes includ ing complications has also been
available to clinicians from laboratory exp erim ents, clinical emphasized. Importantly, for both the surgeon and the
trials, ep id em iology, and health services research. The patient, a system of surgical accountability that focuses on
Institute of Med icine has id entified five major areas in blaming individuals has a poor prospect of significant
w hich inform ation technology cou ld contribu te to safer improvement. Contemporary surgical morbidity and mortal-
health care d elivery: (a) access to the m ed ical know led ge ity conferences must reflect this realization. The prevention,
base; (b) com p u ter-aid ed d ecision sup port system s; (c) col- reporting, analysis, and minimization of surgical harm can
lection and sharing of clinical inform ation; (d ) red u ction in only occur in learning environments, not those of blame and
errors; and (e) enhanced patient and clinician comm u nica- reprisal. The moral imperative to improve patient care to the
tion (5). With the p rop er ap p lication of new tools, fru itfu l extent humanly possible implies that surgical complications
strategies can be d evelop ed for im p rovem ent in su rgical w ill remain a major focus area for surgeons. These changes
ou tcom es, w hich is d iscussed further in Chapter 8. also mean that new texts on this subject must include new
The Internet has led to a great su rge in m ed ical con- perspectives to remain relevant to contemporary practice.
su merism . An estim ated 70 m illion Am ericans sou ght
health care inform ation online in 2000 (6). These nu m bers
continu e to increase. Med ical IT users d em and both sou nd
■ REFERENCES
inform ation and convenience in all areas of health com - 1. Sokol DK, Wilson J. What is a su rgical com p lication? [see com m ent].
World J Surg 2008;32(6):942–944.
m erce. Med ical inform ation system s hold great promise for 2. Lind a TK, Janet MC, Molla SD, ed s. To err is human: building a safer health
red uction in su rgical com plications. An inform ed patient is system. Washington, DC: N ational Acad em y Press; 2000.
a safer p atient. 3. Sm ith S, Freeland M, H effler S, et al. The next ten years of health sp end -
ing: w hat d oes the fu ture hold ? The H ealth Expend itu res Projection
Know led ge, technical skill, and jud gment are the foun- Team [see com m ent]. Health Aff 1998;17(5):128–140.
dations of safe surgical care, but do not always prevent com- 4. H artm an M, Martin A, McDonnell P, et al. N ational health sp end ing in
plications. Patients are frequently injured because of flaw s in 2007: slow er d ru g sp end ing contribu tes to low est rate of overall grow th
since 1998. Health Aff 2009;28(1):246–261.
the design of med ical systems. Recognition of the impor- 5. Com m ittee of on Qu ality of H ealth Care in Am erica. Crossing the quality
tance of the system in w hich care is received has led to a re- chasm. Washington, DC: Institute of Medicine National Academy Press;
examination of surgical culture. Increasingly, im provement 2003.
6. Cain M, Mittm an R, Sarasohn-Kahn J. Health e-people: the online consumer
is a result of team efforts in the form of surgical collabora- experience. Oakland , CA: Institu te for the Fu tu re, California H ealth Care
tives, rather than individual technical brilliance. Chapter 9 of Found ation; 2000.
the second edition, “Building successful quality improvement 7. Ad ed eji S, Sokol DK, Palser T, et al. Ethics of su rgical com p lications [see
com m ent]. World J Surg 2009;33(4):732–737.
collaborative,” explicitly recognizes the power of group effort 8. Angelos P. Com plications, errors, and su rgical ethics [com m ent]. World
and cooperation. J Surg 2009;33(4):609–611.
CHAPTER
2
Learning from Unanticipated
Outcomes and Error
Linnea S. Hauge
■ INTRODUCTION learn, I turned to the senior resid ent seated and inquired
about the silence. H is explanation still reverberates: “it’s
Inherent to the stu d y of su rgical com p lications is the chal- relief that it w asn’t any of u s.” There, bu t for the grace of
lenge of learning from them . Su rgery encom p asses layers God , go I . . . not an uncom m on response. Lou d chastising
of com p lexity that rep resent the hu m an system s involved . of the responsible attend ing surgeon after the results of
It is these com p lex layers that create u nm atched learning their op eration became know n by ad ministration pred icted
opp ortu nities. It is these layers that raise expectations for the absence of that su rgeon from the conference. The experi-
perform ance excellence. ence mad e me (and others) very concerned that w e had
Exp ectations for prod u ctive team d ynamics, d ecision- p rogress to make on how w e learn from error in surgery.
making accu racy, technical precision, effective com m u nica- The tenu ou s natu re of health, healthcare systems, and
tion, and comp assionate, qu ality p atient care create a the hum anity of those w ho provid e health care pred ict that
uniqu e learning and perform ance environm ent. Each su r- p atient ou tcom es are not alw ays anticip ated , planned , or
gical p erform ance presents an opportu nity to learn. The satisfactory. It is w id ely recognized that m aking m istakes is
pu rp ose of this chap ter is to optim ize how w e learn from a natu ral p art of learning on the p ath to becom ing a com pe-
error. This chap ter w ill ad d ress the follow ing points: tent p hysician and su rgeon, and that errors are su re to hap-
1. factors that affect how su rgeons learn from u nantici- p en d u ring one’s career. The d iscip line of su rgery em braces
p ated ou tcom es, especially those that involve error, a long-held trad ition of p erform ance review in the M&M,
2. recom m end ations for enhancing learning exp eriences u nm atched by other d iscip lines in its history and m ethod .
that involve error, Messages of excellence and su p eriority color the ed uca-
3. strategies for com m u nicating abou t error w ith p eers, tional experience of those acquiring surgical acu m en—
learners, and p atients, and reasonably so, the stakes are high and p rofessional trad i-
4. m ethod s for cop ing w ith the stressors that accom p any tion and the p u blic w ou ld allow nothing else. It is this
error and recovery from error. intersection of exp ected p erfection and certain fallibility
that creates a cu ltural challenge in ad d ressing error in
Like many surgical learners, one of my earliest—and su rgery—one that is often felt d eep ly and p ersonally by all
most m em orable—exp eriences observing how a surgical involved . These cu ltu ral challenges have been stu d ied and
team manages error w as at Morbid ity and Mortality d escribed by sociologists and su rgeons (1–4).
(M&M) Conference. As the ed u cational faculty “expert” in The process of learning from error is often implicit,
the d epartment, I frequently attend ed M&M Conferences to w hich tend s to inhibit effective learning, communication,
observe the learning environment and method s. On the and coping. An increased aw areness of how physician
morning’s list w as a com p lication in an append ectom y reflection can im prove p atient care and safety reinforces the
w here a Fallopian tube w as mistaken for the append ix. The need for the surgical community to explicitly ad d ress the
resid ent’s recounting of a proced ure gone horribly w rong— p rocess of learning from error and u nanticip ated outcomes.
a Fallopian tube unintentionally removed having been mis-
taken for an app end ix, and the patient communication that
follow ed —elicited p alpable silence from the room of
■ DEFINING ERROR
attend ing surgeons and trainees. My lack of clinical training The d efinitions of an ad verse event, near m iss, error, and
and m y inclination as a relative layp erson to u nd erstand m istake are critical to learning from error. One of the bar-
the patient’s perspective more often than the physician’s riers to learning from error is the failu re to recognize it
mad e m e curiou s abou t the lessons of the case. Confu sed by (5,6). The d efinitions p resented below are those frequ ently
the silence of the room w hen there appeared to be much to u tilized by researchers in error ed u cation and error
m anagem ent.
An ad verse event is d efined as “an u nintend ed inju ry
Linnea S. Hauge: University of Michigan Med ical School, cau sed by m ed ical m anagem ent rather than the u nd erlying
Ann Arbor, MI 48109. d isease or cond ition of the p atient” (7).
5
A near m iss is “any event or situ ation that cou ld have qu ently ad d ressed in su rgery proceed ings than in m ed icine
resulted in an accid ent, inju ry or illness, but d id not, either p roceed ings (20). Trad itional su rgery conference p roceed -
by chance or throu gh tim ely intervention” (8). ings call for resid ents to present their su rgical patients
An error is “an unintend ed act, either of om ission or w hose cou rse of d isease or inju ry resu lted in su rgical com -
comm ission, or an act that d oes not achieve its intend ed p lications and / or d eath. These cases are often selected , in
ou tcom e” (9). An error of execution is d efined as “the fail- ad vance by the conference lead er, for their learning oppor-
u re of a p lanned action to be com pleted as intend ed ,” and tu nities. The case p resentation typ ically inclu d es an
an error of p lanning is “the use of a w rong plan to achieve overview of the p atient’s cou rse of d iagnosis and treat-
an aim ” (9). m ent, a literatu re review of the d isease or p roced u re, cate-
A m istake is d efined by Wu and colleagues as “a com - gorization of the behavior(s) that led to the com plication or
m ission or an om ission w ith p otentially negative conse- d eath, and qu estions and d iscu ssion by au d ience m em bers.
qu ences for the p atient that w ou ld have been ju d ged The M&M Conference m eets Joint Com m ission on Accred -
w rong by skilled and know led geable p eers at the tim e it itation of H ealthcare Organizations (JCAH O) qu ality assu r-
occurred , ind ep end ent of w hether there w ere negative ance requ irem ents and requ irem ents of the Resid ency
consequ ences” (10). Review Com m ittee for Su rgery.
The d iscip line and p rofession of su rgery is resp ected for
its long trad ition of learning from suboptim al ou tcom es in
■ LEARNING FROM ERROR M&M Conferences. The challenge of cap italizing on these
Most m ed ical stu d ents’ and resid ents’ exp osu re to error is learning op p ortu nities that involve ind ivid u al, team, and
casual or d istant observation and frequ ently occu rs w ith- system failu res is p articu larly d ifficu lt becau se of the
ou t d ebriefing or d iscu ssion w ith an attend ing p hysician. ind ivid u al and social factors affecting how failu res are
Stu d ents rarely have the op tion to d irectly observe or p ar- exp erienced , d efined , and ad d ressed in su rgery (2,3). This
ticip ate in team d ebriefing abou t error or error d isclosu re challenge has led su rgical ed u cators to id entify the need to
conversations w ith p atients. Som e institutions have begu n enhance the d ynam ics and form at of the trad itional M&M
to inclu d e form al learning exp eriences in their stu d ent Conference (21–27).
or resid ent cu rricu la (11–15). These courses are in their Surgical educators have documented conference improve-
infancy and tend to be classroom -based w ith little opportu - ments that inclu d e abbreviating p resentations and litera-
nity for gu id ed p ractice, real or sim u lated . The stand ard tu re review s to increase the nu m ber of cases p resented
app roaches for im p licitly learning from error via observa- d uring a session; id entifying faculty mod erators to enhance
tion are not su fficient to p rovid e constru ctive exp erience in au d ience engagem ent; increasing the interactions and
this d om ain. Less than one-fifth of U.S. and Canad ian qu estions d u ring conference; and encou raging resid ent
physicians su rveyed had them selves received form al ed u - p resenters to m eet w ith their attend ing su rgeon in ad vance
cation on d isclosing errors to patients, and 86% w ere inter- of the conference to d iscu ss their case (22,27) Others have
ested in receiving training in error d isclosure (16). The risk attem p ted to im p rove the conference by em p loying anony-
of im p licit lessons abou t error that com e from u ngu id ed m ou s system s for rating d ifferent asp ects of M&M case p re-
observation is that malad ap tive behaviors and error man- sentations, inclu d ing p articip ants’ ratings of com p lication
agem ent strategies m ay d evelop. Withou t skilled attend ing severity in trau m a (28), p eer review ers’ p ercep tions about
surgeon gu id ance or m od eling, ou r surgical learners m ay su rgeon and system p erform ance (23), and qu antifying the
ad opt behaviors and strategies that are barriers to fu tu re efficacy of case p resentations (24).
practice (6,17). Since the Accred itation Council on Grad uate Med ical
Another concern about allow ing surgical learners to be Ed u cation’s (ACGME) 2001 m and ate for resid ency pro-
resp onsible for ind ep end ently id entifying ap p rop riate les- gram s to im plem ent com petency-based cu rricu lu m and
sons abou t error is echoed in the find ings of Arora and assessm ent (also know n as “the com p etencies”), the M&M
colleagu es (18). They stud ied attend ing su rgeons’ and resi- Conference is frequ ently noted as a m eans of ensu ring that
d ents’ percep tions of w hat perform ance d om ains con- resid ents learn practice-based learning and im provem ent.
tribu te to com p etency as a surgeon. Ju nior resid ents p laced Op tim ally, M&M Conferences offer this p otential, althou gh
a low er valu e on a surgeon’s roles as com m unicator and this goal m u st be p art of the conference d esign.
collaborator. This find ing suggests that a lack of role m od - N ational initiatives on im p roving p atient care have
els or learning op p ortunities exist. Or that resid ents m ay yield ed m ethod s for perform ance review and benchm ark-
not place an approp riate priority on seeking learning expe- ing, and su rgeons have incorp orated these m ethod s into
riences to d evelop effective com mu nication skills, esp e- the M&M review p rocess. Researchers at Massachu setts
cially if resid ents are overextend ed on their clinical General H osp ital u tilized the Am erican College of Su r-
resp onsibilities. geons’ N ational Su rgical Qu ality Im provem ent Program
The M&M Conference, “the gold en hou r” of su rgery (N SQIP) d atabase to stu d y rep orting accu racy of com p lica-
(19), is the p rim ary, form al m ethod for learning from error tions at their M&M Conference (29), and fou nd significant
in su rgery. Resu lts of a review of M&M Conferences in u nd er-rep orting of d eaths and com p lications in their M&M
Med icine and Su rgery ind icate that error is m ore fre- p rocess. Ap p roxim ately one of tw o d eaths and three of four
Chapter 2 • Learning from Unanticipated Outcomes and Error 7
com plications reported in the N SQIP d atabase w ere not ■ Cognitive bias
rep orted in the M&M conference. Their results led the
d epartm ent to ad opt use of an M&M d atabase that is m od - Being p art of a su rgical team that has d ealt w ith a bad com -
eled after the N SQIP d atabase. A consistent find ing in error p lication can leave a su rgeon w ith mem ories abou t the
d isclosu re research d em onstrates that, follow ing an error, exp erience and the p atient that can u nd u ly influ ence
many physicians are not likely to tell peers abou t their d ecision-m aking on the next sim ilar p atient. Learning from
error, nor are they likely to confront peers abou t error p ast perform ance is a critical aspect of learning from error.
(5,10,16,30). This find ing su ggests that d ep artm ents that H ow ever, it is these m ost m em orable exp eriences that can
chose to com p are their M&M and N SQIP d atabases w ou ld create biases that m ay negatively affect d ecision-m aking in
d iscover a similar trend of und er-reporting, an ind ication the next sim ilar p atient care exp erience. Croskerry has
that w e have p rogress to m ake in the d esign and cond u ct of su m m arized m ore than 30 typ es of p red isp ositions to
ou r M&M Conferences if ou r goal is to constru ctively learn d ecision-making error as “cognitive dispositions to respond ”
from ou r errors. (CDRs) (34). CDRs are biases that have the potential to
Antonacci and colleagu es created a classification sys- im p act how p hysicians m ake d ecisions and arrive at d iag-
tem for p ostsu rgical ad verse events that they u sed as p art noses. Exam p les of CDRs, each taken from Croskerry’s
of their M&M Conference review (25). Their pu rp ose w as CDR List (34) are given below :
to stand ard ize the m anner in w hich su rgical p erform ance “Anchoring: The tend ency to p ercep tu ally lock onto salient
w as qu antified for the d epartm ent. They follow ed u p that featu res in the p atient’s initial p resentation too early in
end eavor w ith the creation of ind ivid u alized report card s the d iagnostic p rocess, and failing to ad ju st this initial
that w ere u sed in conju nction w ith their M&M Conference im p ression in the light of later information” (34).
proceed ings (26). Fabri and Zayas-Castro also created and “Confirmation bias: The tend ency to look for confirm ing evi-
stu d ied the valid ity of an instru m ent to classify m ed ical d ence to su p p ort a d iagnosis rather than look for d iscon-
errors by frequ ency, type, and severity, to d eterm ine the firm ing evid ence to refu te it, d esp ite the latter often
cau se of errors that led to surgical com plications in their being m ore p ersu asive and d efinitive” (34).
d ep artm ent (31). “Hindsight bias: Know ing the ou tcom e m ay p rofou nd ly
The p rocess of learning from ad verse events and near influ ence the percep tion of past events and prevent a
misses in su rgery M&M Conference is affected not only by realistic ap p raisal of w hat actu ally occu rred . . . . it m ay
the cu ltu re of su rgery, but by the cultu re of the conference, com p rom ise learning throu gh either an u nd erestim a-
d ep artm ent and institu tion. Role m od eling is perhap s the tion (illu sion of failu re) or overestim ation (illu sion of
most d om inant ed ucational force for learning about profes- control) of the d ecision m aker ’s abilities” (34).
sionalism (17). M&M Conferences are opp ortu nities for “Order effects: Inform ation transfer is a U-fu nction: w e tend
surgeons, esp ecially senior facu lty, to m od el error recogni- to rem em ber the beginning p art (prim acy effect) or the
tion, error d isclosu re, and “constru ctive responses to their end (recency effect). Prim acy effect m ay be augm ented
ow n errors” (32). The m anner in w hich M&M Conferences by anchoring. In transitions of care, in w hich informa-
are cond u cted are w id e-ranging and contribu te signifi- tion transferred from p atients, nu rses, or other physi-
cantly to the opportunities to learn and recover from error. cians in being evalu ated , care shou ld be taken to give
Effective conference m anagem ent and facu lty m od eling d u e consid eration to all inform ation, regard less of the
reinforces m ore thorou gh and accu rate rep orting of errors ord er in w hich it w as p resented ” (34).
and near m isses, and w ill result in enhanced learning
opportunities. The use of anonymous, problem- and system- Croskerry review ed th e literatu re on the CDR p he-
focused approaches for reporting complications and review - n om en a to raise aw areness an d to p rovid e strategies for
ing surgical team perform ance has prom ise for enhancing red u cing error. H e refers to these strategies as “cogn itive
the op p ortu nity to learn and im p rove as a resu lt of M&M d ebiasing” and ad vises p hysicians to seek tim ely feed -
conference p articipation. Surgeons can d raw on the w is- back, u se m em ory aid s, reflect on th e thin king p rocess
d om offered by a principle from the negotiation literature: u sed in d ecision -m akin g, and consid er altern ative d iag-
be hard on the p roblem , easy on the people (33). n oses (34). H e also recom m end s review in g the list of
CDRs and w riting abou t one’s ow n clinical exam p les to
h elp d eterm ine how each CDR m ay p red isp ose one to
■ PREDISPOSITIONS TO ERROR error.
Learning from error requ ires reflection on past perform -
ance and id entifying w hen w e are m ost vulnerable to m ak-
ing an error. Many researchers in su rgery, m ed ical
■ Fatigue
ed u cation, and hum an factors have stu d ied the cond itions Since the introd u ction and im p lem entation of d u ty hou rs
that set the stage for error. These cond itions inclu d e fatigu e regu lations in grad u ate m ed ical ed u cation, the relation-
and overw ork, stress, w ork interrup tions, team d iscord ship betw een fatigu e and m ed ical error has received
and conflict, inexperience, self-assessm ent inaccu racy, and increased interest. Althou gh the link betw een p atient care
cognitive bias. and p hysician fatigu e has not been w ell-established (35),
the p otentially d evastating effect that fatigu e can have on w ork in solo, red u cing the op p ortu nities for com p arison
physician p erform ance has (36). Su rveys of physicians or d iscu ssion w ith p eers and increasing the p rop ensity for
ind icate that their fatigue has contribu ted to error and near self-assessment inaccuracies. The problem of self-assessment
misses in p atient care (37). Well-d esigned stud ies yield con- inaccu racy is com p ou nd ed by one’s inability and varies
sistent find ings that fatigu e has a d etrim ental effect on cog- by task. H igher-level p erform ers tend to be m ost accu rate
nitive and psychomotor performance in surgery, m anifested in their self-assessm ents, often m aking slight u nd eresti-
by increased error and slow er perform ance on technical m ations of their p erform ance. On the other hand , the
tasks (38–41). Finally, an oft-cited cause of error in su rgery, low est-level p erform ers tend to greatly overestim ate their
especially the op erating room (OR), is com m u nication fail- p erform ance (55,56). All levels of su rgical p erform ers are
ure (42–47). The research on fatigue yield s consistent find - vu lnerable to self-assessm ent inaccu racies or m isju d g-
ings that fatigue is a com m on contribu tor to physicians’ m ent abou t their ow n sp ecific abilities. H ow ever, those
and m ed ical stu d ents’ com m unication failu re (5,35,37,48). su rgeons w ith the least exp erience are at p articu lar risk of
Details are forgotten, hand -off protocols are truncated , self-assessm ent inaccu racy d u e to their lack of know led ge
patience w anes, and com m u nication failu re occurs. One of and skill that serve as the basis for self-assessm ent. Fu r-
the greatest challenges in d ealing w ith fatigu e in su rgery is therm ore, the least exp erienced , in efforts to p reserve p ro-
that m any su rgeons believe that they are not su sceptible to fessional cred ibility, are often hesitant to ask for help
fatigue the w ay that others are. A stu d y of surgical and w hen they recognize it is need ed (57).
nonsurgical resid ents w as cond ucted to investigate
trainees’ p ercep tions abou t the im p act that sleep d ep riva-
tion has on their p erform ance, and the results d em onstrate ■ Stress
that su rgery resid ents m ay be less w illing to recognize their Stress is a p red isp osing factor for error in su rgery, and su r-
performance lim itations that are d ue to fatigu e (49). The geons generally recognize how it can affect p erform ance in
cu ltu re of su rgery contribu tes to the m aintenance of these the OR (47,58). LeBlanc d escribes the m anner in w hich
m isbeliefs—m aking it d ifficu lt to im plem ent strategies for stress can im pact m emory and negatively im pact retrieval,
fatigue-cau sed error red u ction, and reinforcing silence m em ory consolid ation, and retention (59). For exam ple,
am ong su rgical learners w hen they recognize that they are remem bering d etails of patient care that occurred d uring a
in a risky, fatigu ed state. highly stressfu l event su ch as a cod e m ay be d ifficu lt. The
Inexp erience is an expected cau se of m ed ical error, and w orking m em ory becom es less reliable in situ ations stress-
heightened su pervision of the least experienced surgeons fu l enou gh that a p erform er p rod u ces stress cortisol. In
is stand ard in m ed ical and su rgical ed u cation. The arrival cond itions of high stress, qu ick recall of p atient d etails m ay
of m ore than 20,000 inexperienced interns and the d ep ar- be com p rom ised . Another exam p le of how stress affects the
tu re of the m ost exp erienced trainees in the United States w orking m em ory is d erived from one of LeBlanc’s earlier
on Ju ly 1 create a su pervisory challenge. The transition w orks u sing sim ulation to stud y param ed ics’ d rug calcu la-
tim e betw een the end of an acad em ic year and the start of a tions und er low -stress and sim u lated high-stress cond i-
new acad em ic year has been the focu s of attention for ind i- tions (60). The p aram ed ics w orking u nd er the sim u lated ,
vid u al and team p red isp osition to p erform ance d eficits. high-stress cond ition m ad e significantly m ore calcu lation
The onslau ght of new p hysicians at the beginning of the errors than the p aram ed ics w orking in low -stress cond i-
acad em ic year raises concern about relative novices’ vu l- tions, d esp ite their level of exp erience. The increase in
nerabilities to error in patient care. Stud ies of the “Ju ly p he- errors w as attribu ted to the w orking m em ory’s vu lnerabil-
nom enon” (50) have yield ed m ixed resu lts, althou gh ity to stress. Sim ilar to fatigu e, the challenges in ad d ressing
researchers utilizing large d atabases have id entified this pred isposition to error in su rgery are the cultu ral
increased rates of u nd esirable events at the beginning of beliefs that su rgeons are im m u ne to the effects of stress.
the surgical trainees’ acad em ic year in Eu rope (51,52) and This environm ent m akes it d ifficu lt for trainees to ad m it
the United States (53,54). their vulnerabilities and to recognize errors that are related
to stress-ind uced m em ory failu re.
■ Self-assessment inaccuracy
Self-assessm ent inaccu racy, the m isju d gm ent one m akes
■ Interruptions
abou t one’s ow n abilities, can contribu te to an ind ivid - Interru p tions to w ork and w orkflow p red isp ose a health-
u al’s su scep tibility to error. In su rgery, this is often care team to error. These m ay occu r d u rin g conversation s
d escribed as “not know ing one’s lim its.” All hu m ans are abou t p atient care, hand over betw een team m em bers, or
su scep tible to inaccu racy in self-assessm ent—w e tend to in su rgery, d u ring an op eration or resu scitation . Effec-
overestim ate ou r p ositive traits and abilities, and u nd er- tively m an agin g interru p tion s, esp ecially d u ring critical
estim ate ou r w eaknesses. It is the intersection of this step s of a d ifficu lt op eration, is a skill that m u st be
hu m an flaw w ith high-d em and , high-risk w ork environ- acqu ired early in su rgical training, as the w ork of
m ents that can becom e a p roblem . Physicians frequ ently interns is frequ ently interru p ted . Clinical hand -offs and
op erating are each su scep tible to error cau sed by inter- p roced u re or tim e has p assed since the last p erform ance, a
ru p tions (47,61,62). com bination of read ing and verbal or m ental rehearsal
shou ld be d one. Verbal rehearsal entails listing the steps of
the p roced u re in correct ord er. Mental rehearsal or practice
■ Communication breakdown involves im aging, w here one sees him self p erform ing the
Breakdown in team communication is a major cause of error step s of the p roced u re in ord er. Mental rehearsal of the pro-
and near misses in med icine and surgery (42–47). A break- ced u re and contingency p lans relevant to the p roced u re is
dow n in communication may occur d ue to absence of com- recom m end ed . Ad d itionally, technical w arm -up s have been
munication, communication of misinformation, or exchanges show n to yield better su rgical p erform ance (66).
between team members that cause team discord . Rogers and Managing intraop erative stress, esp ecially in crises, is
Lingard have described conflict in surgery and strategies for im p ortant to safe p erform ance in the OR (47,58,67,68).
managing conflict (63). Task conflict is disagreement about Recognition of stress is the first step in su ccessfu lly apply-
how to complete a task or solve a problem, such as manage- ing cop ing techniqu es. Exp erienced su rgeons u se a range
ment of a patient’s postoperative care. Interpersonal conflict of techniqu es that they d evelop over the cou rse of their
is dissension that develops between tw o or more ind ividuals careers. It w ou ld be beneficial to d esign p rogram s to learn
and manifests itself in anger, frustration, or friction. In the abou t stress d u ring resid ency training (47). Music and
OR, common “causes of interpersonal conflict include time, hu m or are com monly used m eans of allaying stress and
resources, roles, safety, and situation control” (63). Either of becau se both are shared w ith other team m embers, consid -
these types of conflict has the potential to make a healthcare eration should be given to team d ynam ics in selection of
team more susceptible to error. Team d ynamics that prohibit m u sic and u se of hu m or. Stretching, p rogressive m u scle
active listening, an open exchange of ideas, and subord i- relaxation, m ental rehearsal, and p ositive self-talk are
nates’ participation create an environment for communica- strategies su ccessfu lly em p loyed in other arenas and m ay
tion failu res that resu lt in error. Managing conflict requ ires be u sefu l to m itigate stress in su rgery.
a su rgeon be able to effectively resp ond to it and control Effectively red u cing the risk im p osed by com m u nica-
em otions, avoid reactionary responses, problem -solve, tion breakd ow ns w ill requ ire com m u nication betw een
listen w ithou t interrup ting, and negotiate in an exp ed ited healthcare team m em bers that is “against the au thority gra-
manner (63). d ient” (69). Discou rse betw een attend ing su rgeons and res-
id ents and nurses w ou ld forego the hierarchical trad itions
in su rgery, so that all team m em bers, d esp ite their author-
■ STRATEGIES FOR REDUCING RISK ity, cou ld ask qu estions and offer observations and sugges-
AND SUSCEPTIBILITY tions abou t the p roced u re or case, w ithou t the fear of
intim id ation or retribu tion. This m anner of d iscourse is key
One of the best strategies for red u cing risk is to be aw are of
to safe team com m u nication in and ou t of the OR. Com m u -
situ ations that m ake one m ore vu lnerable to error and
nication strategies to m aintain and enhance effective team
these m ay vary for every ind ivid ual. Id entify the error-
p erform ance can be d isp layed in the follow ing w ays:
related variables that your behaviors influ ence (e.g., OR
environm ent, rep orting com plications). Be aw are of you r 1. Be w illing to engage others’ op inions and id eas.
CDRs and you r pred ispositions d ue to past exp eriences. 2. Use problem -solving to m anage conflict.
Em p loy strategies su ch as self-m onitoring, reflection, seek- 3. Prioritize interru p tions and u se colleagu es to help m an-
ing feed back, and engaging peers in d iscu ssing cases. Self- age them and recover from them .
monitoring is “aw areness, in the m oment, of w hether or 4. Be an active listener.
not the cu rrent situ ation is going w ell” (64). Mou lton’s 5. Em p loy checklist-d riven briefing p rotocols before every
d escrip tion of expert surgeon behavior term ed as “slow ing op eration.
d ow n w hen you shou ld ” is an exam ple of self-m onitoring 6. Debrief after su rgical p roced u res esp ecially if you have
and d escribes an expert surgeon’s cognitive and p sy- stu d ent or resid ent learners or new staff. Ad d ress critical
chom otor action w hen they recognize that they need to events. Provid e and invite feed back abou t w hat w ent
reassess or p rep are for a d ifficu lt part of an operation (65). w ell and w hat cou ld be im p roved .
Reflection is d eliberate u se of cognitive energy to exploring 7. Learn and u se healthcare team m em bers’ nam es. Intro-
and elaborating how one u nd erstand s a problem (64). A d u ce team m em bers in the OR.
reflection abou t a p atient w ith a su rgical infection that 8. If you are w orking w ith resid ents or stud ents in the OR,
becam e sep tic w ou ld elicit qu estions abou t how the p atient ask them —before the case—abou t how they feel about
acqu ired the infection and how it d eteriorated . the case, their exp erience, and their p rep aration for it. If
Preparing for the OR is a critical aspect of surgical per- this qu estion d oes not elicit a u sefu l resp onse, ask them
form ance, and each su rgeon d evelops their ow n rou tine of to verbally rehearse the key step s of the p roced ure. This
prep aration. In ad d ition to clinical requirem ents related to “self-efficacy check” w ill p rovid e insight abou t the
the p atient, review step s of the cases, by read ing or by ver- extent of gu id ance, p rom p ts, and su p ervision that w ill
bal or m ental rehearsal. If one is not yet experienced in a be need ed .
■ LEARNING ABOUT ERROR THROUGH qu acy com m only accom pany recognition of an error
(72–74). Cop ing w ith the range of em otions is an im p ortant
OBSERVATION
step in resolu tion, and su p p ort from a confid ante or
Perform ing an anastom osis, d iagnosing an insu linom a, throu gh an established grou p p rocess can be help fu l in this
managing hyp ovolem ic shock . . . the m ethod s that su r- p rocess. It is recom m end ed that a p hysician id entify a con-
geons m ost frequ ently em ploy to learn these skills are fid ante w ho is know led geable abou t error bu t has no role
observation, p ractice in sim u lated situ ations, su pervised in evalu ation of the ind ivid u al’s p erform ance. This confi-
practice w ith p atients, instru ction and guid ance from an d ante w ou ld be selected , ad visably in ad vance of need , for
experienced su rgeon. Unfortu nately, the lessons abou t the p u rp ose of having a tru sted ind ivid u al w ith w hom to
learning from error and coping w ith error are not typ ically confid entially d iscu ss an error, w hen one occu rs. A confi-
as exp licit or su p ervised . The natu re of learning from error d ante w ou ld be available to review d ecision-m aking and
is uniqu e, and observation, if d irected , can be an effective p rovid e reassu rance. Physicians affected by error often
teaching m ethod . Su rgeons learn abou t professionalism rep ort feeling u ncom fortable talking w ith colleagu es abou t
throu gh observing role m od els (17) and Band u ra’s social m istakes (6,30,74) and id entifying a confid ante in ad vance
learning theory p osits, “m ost hum an behavior is learned of need increases the op tions for cop ing after an error and
observationally throu gh m od eling: from observing others, p erhap s the likelihood that recovery w ill be less stressful.
one form s an id ea of how new behaviors are p erform ed , Op en, honest d isclosu re of the error to colleagu es,
and on later occasions this cod ed inform ation serves as a learners, and the p atient is another im p ortant step in the
guid e for action” (70). The cond itions that are necessary for p rocess of resolu tion as it p revents isolation and initiates
effective mod eling and teaching are relevant for learning the beginning of learning from the error. Fear of litigation
som e of the m ost im portant lessons in surgery—learning often inhibits d isclosu re. H ow ever, as error d isclosure poli-
from and cop ing w ith error. There are m any exam p les of cies and p roced u res are ad op ted , there is grow ing evid ence
theory-based teaching strategies that one can u se: that few er law su its occu r at institu tions w here error d isclo-
su re is p art of the institu tion’s norm s and p ractices (75–78).
1. Direct learners’ attention tow ard critical yet level-
An ap ology throu gh w hich the physician accepts
approp riate asp ects of an error situation.
resp onsibility and affirm s to a p atient that there w as no
2. Allow learners the opp ortunity to observe or be d irectly
intent to err is an im portant asp ect of resolu tion for the
involved in d iscu ssion of error, w hen approp riate.
p hysician and the p atient. A p hysician shou ld , how ever,
3. Give learners the op p ortu nity to verbally review and
m aintain reasonable exp ectations for p atient resp onse to
critiqu e observations of p erform ances.
d isclosu re and ap ology. Patient resp onses vary from grati-
4. Create a blam e-free, team ap proach to review ing and
tu d e to anger, and being p rep ared to hear and allow those
learning from error.
resp onses can help to ensu re a m eaningfu l, p rod u ctive con-
5. Debrief abou t you r ow n experiences, past or p resent,
versation. The H arvard Fu ll Disclosu re Working Group
w ith learning from and cop ing w ith error.
ou tlines the “4 Step s to Fu ll Com mu nication” and recom -
m end s the follow ing:
■ COPING AND RECOVERY FROM ERROR “Tell the p atient and fam ily w hat hap p ened .
Take responsibility.
Errors in m ed icine are both “inevitable and red ucible” (71).
Apologize.
Resu lts of a su rvey of m ore than 3,000 physicians abou t
Exp lain w hat w ill be d one to p revent fu tu re events” (79).
their exp erience w ith m ed ical error d ep ict the negative
effect that error has on physicians’ w ell-being and contin- Initiating honest com m unication and provid ing com -
ued practice (16). Physicians “experienced increased stress p assionate p atient care in the event of an error w ill go a
abou t fu tu re errors, loss of confid ence, sleep d ifficu lties, long w ay to facilitate physician recovery from an ad verse
and red u ced job satisfaction” (16). The m ajority (90%) of event. H ow ever, there is mu ch p rogress to be m ad e to
physicians felt that they d id not have ad equ ate supp ort in ensure that the need s of the “second victim ” of m ed ical
coping w ith m ed ical error, and perceived several barriers error, the p hysician, are m et (16,72,73). Institu tions need to
to obtaining cou nseling. More than other specialties, su r- p rovid e accessible resou rces beyond risk m anagem ent for
geons reported that a barrier to obtaining cou nseling after cop ing and recovery from error. Ad d itionally, faculty
med ical error w as that it w as not likely to be helpful (16), a d evelop ment p rogram s in recognizing error, error d isclo-
find ing that m ay be attributable to the cu ltu re of su rgery su re, and cop ing w ith the stress of error are clearly
and the cu rrent state of supp ort system s. w arranted .
Perceived and actual availability of physician and
healthcare team sup port system s are im portant for resolu -
tion and recovery in the w ake of an error. One m od el of
■ SUMMARY
find ing resolu tion inclu d es recognizing an error, d isclosing Error in m ed icine is inevitable. It is ou r resp onsibility to
it, apologizing for it, and m aking am end s (32). Physician learn from it, and to d o so in w ays that m aintain a p ro-
feelings of rem orse, guilt, fear, hum iliation, and inad e- d u ctive learning and w ork environm ent. Constru ctive
team - and system-based approaches to learning from error 24. Risu cci DA, Su llivan T, DiRu sso S, et al. Assessing ed u cational valid ity
of the m orbid ity and m ortality conference: a p ilot stu d y. Curr Surg
are important to effective learning and error reduction. The 2003;60:204–209.
M&M Conference is an opportunity to improve how w e 25. Antonacci AC, Lam S, Lavarias V, et al. A m orbid ity and m ortality
learn from error. Being aware of predispositions to error conference-based classification system for ad verse events: su rgical
ou tcom e analysis: p art I. J Surg Res 2008;147:172–177.
facilitates efforts to ad d ress systems issues—systems issues 26. Antonacci AC, Lam S, Lavarias V, et al. A rep ort card system u sing
that unnecessarily allow humans to err. Mod eling profes- error profile analysis and concurrent m orbid ity and m ortality review :
sional behaviors, such as self-monitoring and com passion- su rgical ou tcom e analysis: p art II. J Surg Res 2008;153:95–104.
27. Mu rayam a K, Derossis A, DaRosa D, et al. A critical evalu ation of the
ate honesty in d isclosure, will serve us and our learners w ell. m orbid ity and m ortality conference. Am J Surg 2002;183:246–250.
28. Dissanaike S, Berry M, Ginos J, et al. Variations in the p ercep tion of
traum a-related com p lications betw een attend ing su rgeons, su rgery
■ REFERENCES resid ents, critical care nu rses, and m ed ical stu d ents. Am J Surg 2009;
197:764–768.
1. Katz P. The scalpel’s edge: the culture of surgeons. N eed ham H eights, MA: 29. H u tter MM, Row ell KS, Devaney LA, et al. Id entification of su rgical
Allyn & Bacon; 1999. com plications and d eaths: an assessm ent of the trad itional su rgical
2. Bosk C. Forgive & Remember, 2nd ed . Chicago: University of Chicago m orbid ity and m ortality conference com p ared w ith the Am erican Col-
Press; 2003. lege of Su rgeons-N ational Su rgical Qu ality Im p rovem ent Program .
3. Gaw and e A. Complications: a surgeon’s notes on an imperfect science. N ew J Am Coll Surg 2006;203:618–624.
York, N Y: Picad or; 2002. 30. Gallagher TH , Waterm an AD, Ebers A, et al. Patients’ and p hysicians’
4. Gaw and e A. Better: a surgeon’s notes on performance. N ew York, N Y: attitu d es regard ing the d isclosu re of m ed ical errors. JAMA 2003;289:
Picad or; 2007. 1001–1007.
5. Wu AW, Folkm an S, McPhee SJ, et al. Do hou se officers learn from their 31. Fabri PJ, Zayas-Castro JL. H u m an error, not com m u nication and sys-
m istakes? Qual Saf Health Care 2003;12:221–228. tem s, u nd erlies su rgical com p lications. Surgery 2008;144:557–563; d is-
6. H obgood C, H evia A, Tam ayo-Sarver JH , et al. The influ ence of the cussion 563–565.
causes and contexts of m ed ical errors on em ergency m ed icine resi- 32. Pollack C, Bayley C, Mend iola M, et al. H elp ing clinicians find resolu -
d ents’ responses to their errors: an exp loration. Acad Med 2005;80: tion after a m ed ical error. Camb Q Healthc Ethics 2003;12:203–207.
758–764. 33. Fisher R, Ury W. Getting to yes. N ew York, N Y: Pengu in Books; 1991.
7. Brennan T, Leap e L, Laird N . The natu re of ad verse events in hosp ital- 34. Croskerry P. The im portance of cognitive errors in d iagnosis and strate-
ized patients: results from the H arvard m ed ical p ractice stu d y. N Engl J gies to m inim ize them . Acad Med 2003;78:775–780.
Med 1991;324:2377–2384. 35. Fletcher KE, Davis SQ, Und erw ood W, et al. System atic review : effects
8. Kohn KT, Corrigan JM, Donald son MS. To err is human: building a safer of resid ent w ork hou rs on p atient safety. Ann Intern Med 2004;141:851–
health system. Washington, DC: N ational Acad em y Press; 1999. 857.
9. Reason J. Human Error. N ew York, N Y: Cam brid ge University Press, 36. Lockley SW, Barger LK, H arvard Work H ou rs, H ealth and Safety
1990. Grou p et al. Effects of health care p rovid er w ork hou rs and sleep d ep ri-
10. Wu AW, Cavanau gh TA, McPhee SJ, et al. To tell the tru th: ethical and vation on safety and p erform ance. Jt Comm J Qual Patient Saf 2007;33:
practical issu es in d isclosing m ed ical m istakes to p atients. J Gen Int Med 7–18.
1997;12:770–775. 37. West CP, Tan AT, H aberm ann TM, et al. Association of resid ent fatigu e
11. Brannick MT, Fabri PJ, Zayas-Castro J. Evalu ation of an error-red uction and d istress w ith p erceived m ed ical errors. JAMA 2009;302:1294–1300.
training program for su rgical resid ents. Acad Med 2009;84:1809–1814. 38. Gaw and e A, Zinner MJ, Stu d d ert DM, et al. Analysis of errors rep orted
12. Paxton JH , Ru binfeld IS. Med ical errors ed u cation for stu d ents of by su rgeons at three teaching hosp itals. Surgery 2003;133:614–621.
surgery: a p ilot stu d y revealing the need for action. J Surg Educ 2009; 39. Gerd es J, Kahol K, Sm ith M, et al. The effect of fatigu e on cognitive and
66:20–24. psychom otor skills of trau m a resid ents and attend ing su rgeons. Am J
13. N ew ell P, H arris S, Au fses A Jr, et al. Stu d ent p ercep tions of m ed ical Surg 2008;196:813–819.
errors: incorporating an explicit p rofessionalism curriculum in the 40. Kahol K, Satava RM, Ferrara J, et al. Effect of short-term p retrial p rac-
third -year su rgery clerkship . J Surg Educ 2008;65:117–119. tice on surgical proficiency in sim u lated environm ents: a rand om ized
14. Keller DR, Bell CL, Dottl SK. An effective cu rricu lu m for teaching trial of the ‘p reop erative w arm -u p ’ effect. J Am Coll Surg 2009;208:255–
third -year m ed ical stu d ents abou t m ed ical errors and d isclosu re. WMJ 268.
2009;108:27–29. 41. Eastrid ge BJ, H am ilton EC, O’Keefe GE, et al. Effect of sleep d ep riva-
15. H albach JL, Su llivan LL. Teaching m ed ical stu d ents abou t m ed ical tion on the p erform ance of sim u lated lap aroscop ic su rgical skill. Am J
errors and patient safety: evalu ation of a requ ired cu rricu lu m . Acad Surg 2003;186:169–174.
Med 2005;80:600–606 42. ElBard issi AW, Wiegm ann DA, H enrickson S, et al. Id entifying m eth-
16. Waterm an AD, Garbu tt J, H azel E, et al. The em otional im p act of m ed - od s to im prove heart surgery: an operative ap proach and strategy for
ical errors on practicing p hysicians in the United States and Canad a. Jt im p lem entation on an organizational level. Eur J Cardiothorac Surg
Comm J Qual Patient Saf 2007;33:467–476. 2008;34:1027–1033.
17. Park J, Wood row SI, Reznick RK, et al. Observation, reflection, and 43. Rogers SO, Gaw and e AA, Kw aan M, et al. Analysis of su rgical errors in
reinforcem ent: su rgery faculty m em bers’ and resid ents’ perceptions of closed m alp ractice claim s at 4 liability insu rers. Surgery 2006;140:25–33.
how they learned p rofessionalism . Acad Med 2010;85:134–139. 44. Greenberg CC, Regenbogen SE, Stu d d ert DM, et al. Patterns of com -
18. Arora S, Sevd alis N , Su lim an I, et al. What m akes a com p etent su rgeon? m unication breakd ow ns resu lting in inju ry to su rgical p atients. J Am
exp erts’ and trainees’ p ercep tions of the roles of a su rgeon. Am J Surg Coll Surg 2007;204:533–540.
2009;198:726–732. 45. Christian CK, Gu stafson ML, Roth EM, et al. A p rosp ective stu d y of
19. Gord on LA. Gordon’s guide to the surgical morbidity and mortality confer- patient safety in the op erating room . Surgery 2006;139:159–173.
ence. Philad elp hia, PA: H anley & Belfu s; 1994. 46. Lingard L, Esp in S, Whyte S, et al. Com m u nication failu res in the op er-
20. Pierlu issi E, Fischer MA, Cam p bell AR, et al. Discu ssion of m ed ical ating room : an observational classification of recurrent typ es and
errors in m orbid ity and m ortality conferences. JAMA 2003;290:2838– effects. Qual Saf Health Care 2004;13:330–334.
2842. 47. Arora S, H u ll L, Sevd alis N , et al. Factors com p rom ising safety in su r-
21. H arbison SP, Regehr G. Facu lty and resid ent op inions regard ing the gery: stressfu l events in the op erating room . Am J Surg 2010;199:60–65.
role of m orbid ity and m ortality conference. Am J Surg 1999;177: 48. Brow n R, Du nn S, Brnes K, et al. Doctors’ stress resp onses and p oor
136–139. com m u nication perform ance in sim ulated bad -new s consultations.
22. Prince JM, Vallabhaneni R, Zenati MS, et al. Increased interactive for- Acad Med 2009;84:1595–1602.
m at for m orbid ity and m ortality conference im proves ed u cational 49. Wood row SI, Park J, Mu rray BJ, et al. Differences in the p erceived
value and enhances confid ence. J Surg Educ 2007;64:266–272. im pact of sleep d eprivation am ong su rgical and non-surgical resid ents.
23. Bend er LC, Klingensm ith ME, Freem an BD, et al. Anonym ou s grou p Med Educ 2008;42:459–467.
p eer review in su rgery m orbid ity and m ortality conference. Am J Sur 50. N ash R. The “killing season”: d oes inexp erience cost lives? (Com m ent).
2009;198:270–276. Lancet 2009;347:1313–1314.
51. H aller G, Myles PS, Taffe P, et al. Rate of u nd esirable events at begin- 65. Mou lton CA, Regehr G, Lingard L, et al. ‘Slow ing d ow n w hen you
ning of acad em ic year: retrosp ective cohort stu d y. BMJ 2009;339: should ’: initiators and influ ences of the transition from the rou tine to
b3974. the effortful [p ublished online ahead of p rint March 23, 2010]. J Gas-
52. Jen MH , Bottle A, Majeed A, et al. Early in-hosp ital m ortality follow ing trointest Surg 2010;14(6):1019–1026.
trainee d octors’ first d ay at w ork. PLoS One 2009;4:e7103. 66. Kahol K, Leyba MJ, Deka M, et al. Effect of fatigu e on p sychom otor and
53. Englesbe MJ, Pelletier SJ, Magee JC, et al. Seasonal variation in su rgical cognitive skills. Am J Surg 2008;195:195–204.
outcom es as m easured by the Am erican College of Su rgeons-N ational 67. Arora S, Sevd alis N , N estel D, et al. Managing intraop erative stress:
Surgical Qu ality Im p rovem ent Program (ACS-N SQIP). Ann Surg 2007; w hat d o su rgeons w ant from a crisis training program ? Am J Surg
246:456–462. 2009;197:537–543.
54. Inaba K, Recinos G, Teixeira P, et al. Com p lications and d eath at the 68. Yu le S, Flin R, Paterson-Brow n S, et al. N on-technical skills for su r-
start of the new acad em ic year: is there a “Ju ly p henom enon”? J Trauma geons in the op erating room : a review of the literatu re. Surgery
2010;68:19–22. 2006;139:140–149.
55. Ehrlinger J, Johnson K, Banner M, et al. Why the u nskilled are u naw are: 69. Etchells E, O’N eill C, Bernstein M. Patient safety in su rgery: error
further explorations of (absent) self-insight am ong the incom petent. d etection and prevention. World J Surg 2003;27:936–941.
Organ Behav Hum Decis Process 2008;105:98–121. 70. Band u ra A. Self-efficacy: the exercise of control. N ew York, N Y: W. H .
56. Kruger J, Du nning D. Unskilled and u naw are of it: how d ifficu lties in Freem an; 1997.
recognizing one’s ow n incom petence lead to inflated self-assessm ents. 71. Pilp el D, Schor R, Benbassat J. Barriers to accep tance of m ed ical error:
J Pers Soc Psychol 1999;77(6):1121–1134. the case for a teaching program . Med Educ 1998;32:3–7.
57. Kenned y TJ, Regehr G, Ross Baker G, et al. Preserving p rofessional 72. Wu AW. Med ical error: The second victim (ed itorial). BMJ 2000;320:
cred ibility: ground ed theory stu d y of m ed ical trainees’ requ ests for 726–727.
clinical su pp ort. BMJ 2009;338:b138. 73. Schw ap p ach DL, Bolu arte TA. The em otional im p act of m ed ical error
58. Wetzel CM, Kneebone RL, Woloshynow ych M. The effects of stress on involvem ent on physicians: a call for lead ership and organizational
su rgical perform ance. Am J Surg 2006;191:5–10. accou ntability. Swiss Med Wkly 2008;138(1–2):9–15.
59. LeBlanc VR. The effects of acu te stress on p erform ance: im p lications for 74. Christensen JF, Levinson W, Du nn PM. The heart of d arkness: the
health p rofessions ed ucation. Acad Med 2009;84:S25–S33. im pact of perceived m istakes on p hysicians. J Gen Intern Med 1992;7:
60. LeBlanc VR, McArthu r B, King K, et al. Param ed ic p erform ance in cal- 424–431.
culating d ru g d osages follow ing stressfu l scenarios in a hu m an patient 75. Clinton H R, Obam a B. Making p atient safety the centerp iece of m ed -
sim u lator. Prehosp Emerg Care 2005;9:439–444. ical liability reform . N Engl J Med 2006;354:2205–2208.
61. Liu D, Gru nd geieger T, Sand erson PM, et al. Interru p tions and blood 76. Boothm an RC, Blackw ell A, Cam p bell D Jr, et al. A better ap p roach to
transfu sion checks: lessons from the sim u lated op erating room . Anesth m ed ical m alp ractice claim s? The University of Michigan exp erience.
Analg 2009;108:219–222. J Health Life Sci Law 2009;2:125–159.
62. William s RG, Silverm an R, Schw ind C. Su rgeon inform ation transfer 77. Kram an SS, H am m G. Risk m anagem ent: extrem e honesty m ay be the
and com m u nication: factors affecting qu ality and efficiency of inp a- best p olicy. Ann Int Med 1999;131:963–967.
tient care. Ann Surg 2007;245:159–169. 78. Gallagher TH . A 62-year-old w om an w ith skin cancer w ho exp erienced
63. Rogers D, Lingard L. Su rgeons m anaging conflict: a fram ew ork for w rong-site su rgery: review of m ed ical error. JAMA 2009;302:669–677.
u nd erstand ing the challenge. J Am Coll Surg 2006;203:568–574. 79. H arvard Fu ll Disclosure Working Grou p . When things go wrong:
64. Eva KW, Regehr G. “I’ll never p lay p rofessional football” and other fal- responding to adverse events. Bu rlington, MA: Massachu setts Coalition
lacies of self-assessm ent. J Contin Educ Health Prof 2008;28:14–19. for the Prevention of Med ical Errors; 2006.
CHAPTER
Surgical Training: Present and Future

Rebecca M. Minter and Paul G. Gauger
■ INTRODUCTION trend . The p resent-d ay grad u ating su rgical resid ent is

resp onsible for d em onstrating exp osu re to an ever-increas-
Three p rom inent them es characterize Am erican m ed icine ing list of p roced u res, lead ing to a p otentially d iffu se and
tod ay. There has been an explosive increase in the basic su p erficial exp erience. Withou t carefu l attention, exposu re
know led ge u nd erlying clinical p ractice. There is a crisis in m ay becom e the ru le, rather than d em onstration of profi-
the m anner in w hich w e d eliver health care. And recent ciency and com p etency w ithin a given d om ain. Current
technologic ad vances are so fu nd am entally com p lex as to com p etency-based cu rricu lar initiatives led by the Su rgical
requ ire m ajor reassessm ent and change in accep ted ed u ca- Cou ncil on Resid ent Ed u cation (SCORE) consortiu m and
tional p arad igm s (1). All these factors have affected the the Am erican College of Su rgeons (ACS) and the Associa-
long-stand ing m od el of Am erican surgical training to cre- tion of Program Directors of Su rgery (APDS) w ill hop efu lly
ate a u niqu e crisis in surgical ed ucation. Table 3.1 contains reverse this trend in the com ing years.
an incom p lete assessm ent of the factors contribu ting to
this crisis.
Althou gh every generation lam ents change, it is not an ■ The emergence of general surgery
overstatem ent to say that su rgical training is u nd ergoing subspecialty practice
more changes and challenges than ever before. As a field
steep ed in trad ition and inherited w isd om , su rgery has General su rgery has grad u ally changed from a broad and
been slow to em brace change; how ever, view ed from the flexible sp ecialty resp onsible for “the skin and its con-
prop er p ersp ective, m u ch of the change is w elcom e and tents” to a m ore lim ited d efinition. Many of the op erations
necessary. Change m u st be m anaged to ensure that the val- form erly p erform ed by the general su rgeon are now being
ues of the p rofession are preserved . To d o so, it is critically p erform ed by a general su rgeon w ith ad d itional fellow -
im portant to u nd erstand the internal and external forces ship training or d eclared interest. The rise in vascu lar,
that have led to this point. Selected influences are exam - end ocrine, and colorectal su rgery p ractices is an exam p le
ined below w ithin the context of su rgical training, and the of this increase in su bsp ecialization. These changes have a
manner in w hich ed u cational p rogram s w ill have to ad apt bearing on the curriculum red esign requ ired to facilitate
are d elineated . sp ecialization and fellow ship training, w hile p reserving
the critical exp eriences requ ired for General Su rgery
■ FORCES AFFECTING SURGICAL TRAINING training.
As surgical training represents a microcosm of m ed ical
■ Increase in number and complexity p ractice, it w as to be exp ected that the sw eep ing changes of
of procedures the last 30 to 40 years have had d ow nstream effects. Med -
ical p ractice has been transform ed into m ed ical ind u stry.
Rem arkable ad vances have been m ad e in the last few
Declining p rofessional reim bu rsem ent, an increased p ace
d ecad es in the u nd erstand ing of d iseases and in the
of clinical p ractice, and d ehu m anization of the p hysician–
options available for treatment. For som e d iseases, su rgical
p atient relationship have taken their toll on practicing
intervention is less com mon (e.g., pep tic u lcer d isease); bu t
p hysicians. The med ical professional is occasionally d emor-
for m any others, factors su ch as earlier d etection have ren-
alized , confu sed , and cynical. Perhap s am p lified by the
d ered som e op erations m ore com m on (e.g., colon cancer).
p erception that surgeons are w orking hard er and being
For nearly all exam ples, the bread th of therapeu tic op tions
p aid less than those in other sp ecialties, d issatisfaction and
has increased significantly. The em ergence of lap aroscop ic
fru stration m ight be vocally and visibly exp ressed d u ring
and end oscop ic technologies has greatly am plified this
the d aily rou tine. As a resu lt, you ng, enthu siastic, im pres-
sionable m ed ical stud ents and trainees find them selves
analyzing their interactions w ith established surgeons and
Rebecca M. Minter, Paul G. Gauger: University of asking, “Why w ou ld I w ant to d o w hat they d o w hen they
Michigan, Ann Arbor, MI 48109. d on’t even w ant to d o w hat they d o?”
13
Table 3 .1 M ed ica l ed u ca t ion issu es , in fl u en ces , and d issatisfaction, and the m ed ical liability crisis fu rther
a n d r esp on sibilit ies test this relationship . This strain is often visible to m ed ical
stu d ents.
General Educational Issues Although trend s su ggesting d eclining interest in surgi-
Explosive increase in medical knowledge cal careers 7 to 10 years ago (2000–2002) ap p eared to por-
Competitive imbalance between workload and educational opportunity tend significant p roblem s, recent m atch statistics suggest
Need for new training paradigms that the trend m ight be reversing, w ith 99.5% to 99.9% of all
ACGME outcome project (competencies)
p ositions being filled over the last 5 to 7 years (Table 3.2). It
Changing expectations of patients and society
has been hyp othesized that lim itations on d u ty hou rs are
Changes in educational techniques and technology (Internet,
simulation, etc.) attracting stu d ents w ho p reviou sly may have been too con-
Sources of innovation outside academic medicine (industry R&D) cerned abou t lifestyle issu es to p u rsu e su rgical training. In
Focus on documentation instead of delivery of care ad d ition, in m any segm ents of the p rofession, this trend
w as noted , analyzed , and sp ecifically ad d ressed w ith inter-
Policy, Administrative, and Financial Issues
Decreased number of applicants for training ventions intend ed to d em onstrate the p leasu re, rew ard ,
Changes in applicant quality and satisfaction associated w ith a su rgical career (3).
Changing demographics of applicant pool
Increased medical school dependence on clinical revenue
Decreased reimbursement for graduate medical education ■ An evolution in the way we learn and teach
Decreased faculty professional reimbursement
Length of training programs
Ad vances in m ed ical p ractice, esp ecially those that d epend
Increased indebtedness of trainees on ad vanced technologies, requ ire skills neither selected
Increased fraction of foreign medical graduates in training programs for nor tau ght in med ical schools and resid encies. In con-
trast to the prod igiou s increase in m ed ical know led ge that
Specific Surgical Training Issues
Ensuring broad exposure to surgical subspecialties
occu rs every year, ou r ability to com p rehend and then
Increased technologic sophistication and dependency on procedures assim ilate this know led ge into m ed ical p ractice is con-
Assessing surgical competency strained . Even the evolu tion of clinical p ractice has been
RRC mandates/standards for case volume during training d riven by technology. Consid er the incorp oration of end o-
Continuity of care/workload scop ic, lap aroscop ic, and robotic technology into cu rrent
Disenchantment with specialty among practitioners su rgical p ractice. It has been a challenge for p racticing sur-
Personal Issues for Trainees geons to learn and m aster the requ isite new skills and m ore
Increased indebtedness of graduates d ifficu lt to d ecid e how best to teach these skills to su rgeons
Low pay in training. Acad em ic m ed icine no longer has a m onopoly
Lack of overtime compensation on innovation and research. Many technological ad vances
Lack of retirement benefits are d riven by ind u stry, w hich changes the d ynam ics of
Length and intensity of training ed u cation and requ ires an ongoing interaction w ith com -
Balance between workload and personal time m ercial entities, and recent national attention regard ing
Decreased income as practitioner to repay loan burden both perceived and real conflicts of interest betw een m ed -
ACGME, Accreditation Council for Graduate Medical Education; R&D, research and
ical p rofessionals and ind u stry has m ad e these relation-
development; RRC, Residency Review Committee. ships even m ore com plicated .
From Zelenock GB. Presidential address: medical education: thoughts on the train- Becau se d eclining reim bu rsem ent exacerbates the eco-
ing of physicians and surgeons. J Vasc Surg 2003;37:921–929, with permission. nom ic crisis in su rgical p ractice, a nearly constant atten-
tion to one’s p ractice is requ ired . Ded icating tim e for
The bu siness of m ed icine can be so all-consu m ing that ed u cation and self-im p rovem ent is increasingly d ifficu lt.
su rgeons m ight find them selves m ore concerned w ith the In ad d ition, su rgical d ep artm ents are the clinical engines
business of cod ing, billing, and reim bursem ent than w ith that d rive the financial m ission of the hosp ital—esp ecially
taking care of p atients. Patients sense this, and accord ingly, in acad em ic health centers. As su ch, the p ace of su rgical
trust is erod ed (2). Med ia exploitation, pu blic percep tion p ractice is often breakneck and the tim e for learning,
Table 3 .2 Percen t a ge of op en su r gica l r esid en cy slot s fi lled a,b

2002 Positions c 2006 Positions 2007 Positions 2008 Positions 2009 Positions
% U.S. % Total % U.S. % Total % U.S. % Total % U.S. % Total % U.S. % Total
Categorical 75.3 94.4 83.3 99.9 78.1 99.8 83.1 99.8 77.4 99.5
Preliminary 38.6 58.1 38.9 60.6 38.1 61.9 41.4 64.0 34.8 58.9
a
The % U.S. columns indicate the % of positions filled by U.S. medical graduates.
b
The % total columns indicate the % of positions filled by U.S. and foreign medical graduates.
c
Indicates nadir of surgical residency positions filled.
Chapter 3 • Surgical Training: Present and Future 15
teaching, reflection, and innovation is critically d im in- grad u ate, and continu ing m ed ical ed u cation. The Bal-
ished . This p ace hu rts both facu lty m em bers and resid ents. anced Bu d get Act of 1997 exacerbated these p roblem s—
As the ed u cational environm ent has changed , so has ed u - esp ecially for grad u ate m ed ical ed u cation (GME)—and
cational technology. As com p u ter-based and Internet- has severely cu rtailed ed u cational resou rces (7). Still,
enabled ed u cational p rogram s continu e to im p rove, it is d irect and ind irect fed eral fu nd s flow to hosp itals—in p art
clear that they w ill soon be the m eans to p rovid e ed u ca- to su p p ort and su bsid ize GME. The im p act the Afford able
tional content at an ind ivid u alized p ace, d ocu m ent con- Care Act of 2010 w ill have on GME fu nd ing is yet to be
tent exp osu re, and evalu ate content m astery. The ability to d eterm ined .
sim u late both p atients and p roced u res has exp onentially
increased ed u cational op p ortu nities for the p resent and
the fu tu re. ■ The social contract of medicine and changes
in the doctor–patient relationship
■ External regulation of the profession and the The p ressures that have led to a perturbed relationship
educational process betw een p hysicians and p atients are comp licated . A few
d ecad es ago, p atients covered u nd er Med icare and Med ic-
When external forces regu late a profession, it nearly
aid u nd erstood that their care might be p rovid ed by physi-
alw ays m eans that the profession has not ad equ ately m an-
cians in training und er the supervision of senior physicians.
aged to d o so itself. Su rgeons have d one an inad equ ate job
This relationship w as an accep ted p art of the social contract
of articu lating w hy the p ractice of su rgery and the im p licit
of med icine. Patients knew that they w ere participants in
training are d ifferent and m u st rem ain d ifferent from other
the ed u cational p rocess of the profession (8). Increasing
specialties. Therefore, su rgical training is now su bject to
afflu ence and consumerism, d issatisfaction w ith the insur-
the sam e grou p of regu lations as all other specialties. In the
ance ind ustry and the “med ical machine,” and a general
w ake of frequ ent and often p oorly coord inated regu lation
increase in a sense of entitlement and empow erment in the
from agencies su ch as the Accred itation Council for Grad u -
American patient population have altered these expecta-
ate Med ical Ed u cation (ACGME), the Resid ency Review
tions. Many patients are no longer interested or w illing to
Com m ittee (RRC), and the Am erican Board of Su rgery
p articipate in the ed ucational p rocess. Many expect their
(ABS), m any p rogram d irectors find them selves mired in
care to be d elivered by the most highly skilled practitioner
regu lations and p ressing changes.
available at all times. Some might misu nd erstand the
Work hou r regu lations have becom e highly p oliticized .
p rocess of sup ervision and qu estion or refuse the participa-
This issu e has grow n in the p u blic eye to center arou nd
tion of trainees in the provision of their care.
concerns of sleep d ep rivation and inad equ ate su p ervision.
The 2000 Institu te of Med icine (IOM) rep ort, To Err Is
Human: Building a Safer Health System, claim ed that m ed - ■ Personal economic factors
ical errors resu lted in 1 m illion p atient inju ries and
nearly 100,000 p atient d eaths each year (4). Althou gh The d efinition of resid ents’ jobs is am bigu ously m ired in a
m any p ossible contribu tors to m ed ical errors w ere consid - no-m an’s land betw een stu d ent and em p loyee. This confu-
ered , this rep ort im p lied a relationship to p hysician w ork- sion is u sed as ju stification for low salaries, lack of retire-
load , fatigu e, lack of alertness, and sleep d ep rivation, and m ent benefits, and inad equ ate w ork facilities and su pport
laid the grou nd w ork for the 2003 d u ty-hou r p olicy issu ed system s. For d ecad es the resid ency years served as a rite of
by the ACGME. In 2008, another rep ort titled Resident Duty p assage and these cond itions w ere tolerated . It w as und er-
Hours: Enhancing Sleep, Supervision, and Safety (5) w as stood that the prestige and affluence afford ed to physicians
issu ed by the IOM. In this rep ort, fu rther significant in p ractice w ou ld act as eventu al comp ensation. An
restrictions on d u ty hou rs w ere recom m end ed for all resi- increasing nu m ber of cu rrent m ed ical school grad u ates d o
d ents in training, regard less of sp ecialty. While w e cu r- not seek ad d itional training and instead leverage their
rently aw ait ACGME’s d eliberations and resp onse to this M.D. d egree for su ccess in related field s. As college friend s
rep ort, it is anticip ated that fu rther restrictions w ill be find early su ccess and happ iness in field s that require only
com ing, ad d ing even greater strain on the system . Unfor- a fraction of the ed u cation and d ed ication that m ed icine
tu nately, ed u cation has becom e a casu alty of this p u blic d oes, it becom es even m ore d ifficu lt to ru n the gau ntlet of
and p olitical d iscou rse, su ch that the tim e that resid ents surgical training.
sp end engaged in sanctioned ed u cational activities is An especially d ifficult factor in this econom ic equation
cou nted against the d u ty-hou rs lim it, w hich only fu rther is m ed ical school grad u ate ind ebted ness. Many stud ents
exacerbates the ed u cational d ilem m a. continu e to carry loan d ebt from u nd ergrad u ate ed u cation.
The average d ebt level of grad u ating Am erican m ed ical
stu d ents is over $100,000. Becau se m ost resid ents d o not
■ A health care system in crisis accru e retirement savings, each ad d itional year of training
It is an accep ted observation that the crisis environm ent is threatens lifetim e earning p otential. Su rgical resid ents, by
esp ecially severe in the acad em ic health centers (6). For virtu e of extensive training and d ecreasing rem uneration,
this reason, the crises m ore d irectly im p act u nd ergrad u ate, are d isp rop ortionately d isad vantaged .
■ Generational values and lifestyle considerations p rofession or p rofessional behaviors. It is p arad oxical
that d u ty-hou r regu lations are being assim ilated into the
It is the archetyp e of the su rgeon to be d ed icated to p atients stru ctu re of su rgical resid ency at the sam e tim e that p rofes-
at any exp ense. Most of the great su rgeons of the last cen- sionalism is one of the ACGME Ed u cational Ou tcom es
tu ry had an u nflagging d ed ication to their p atients and (Com p etencies) to be sep arately tau ght and m easured (11).
their careers. H ow ever, su ch d ed ication, w hile benefiting This ju xtap osition of valu es w ill requ ire m ajor attention
patients, often p enalized surgeons’ m arriage and fam ily and vigilance in the stru ctu re and p ractice of su rgical train-
life. The cu rrent generation of men and w om en pursu ing a ing in the fu tu re, and this strain betw een p rofessional val-
career in su rgery has begu n to reject som e of these valu es. u es m ay becom e even further exacerbated if ad d itional
It is the p ervasive sentim ent of this generation that p er- constraints are p laced on the w ork and d u ty-hou r environ-
sonal hap p iness is a right to be claim ed . Where hap p iness m ent as a resu lt of the m ost recent IOM rep ort (5).
cannot be gu aranteed from one’s career alone, it m ight be Many d evelop ed nations have restrictions on the d u ty
found in leisurely p ursuit of other interests and in a fu lfill- hou rs of p hysicians in training. It is im p ossible to com -
ing fam ily life. These characteristics are influ encing the p letely extrap olate these exp eriences to Am erican su rgery
grow th of “lifestyle” specialties such as d erm atology and becau se of d ifferences in p atient and societal exp ectations,
anesthesiology and w ill be reflected in the w orkstyles of as w ell as d ifferences in trad itions and valu es. In general,
the next generation of su rgeons. While this balance is p osi- m aintaining excellent qu ality su rgical training ap p ears to
tive in m ost regard s, it serves to further alter the cu ltu re of be p ossible, largely becau se of an increase in the nu m ber of
Su rgery, w hich is cu rrently stru ggling w ith an id entity cri- ed u cational resou rces and technologies, w hich can facili-
sis related to m any sim u ltaneou s shifts in p ractice and tate m ore efficient content assim ilation and skill m astery
evolving exp ectations of trainees and patients as com pared (12). In Sw ed en, the d u ty-hou r lim it has been 40 hours per
w ith generations p ast. w eek for 30 years, and p atient ou tcom es ap p ear not to have
su ffered as a resu lt. Becau se of the lim ited hou rs and thu s,
■ Threats to patient safety and the quality and u ltim ately, lim ited exp osu re, the training p eriod has
becom e stru ctu red arou nd tim e-targeted com p etency goals
continuity of care
(13). Cu rricu la have been tightly tailored for sp ecific train-
Society, through its regulatory agencies, has d etermined ing p rogram s. The fu ll im p act of the Eu rop ean Working
that surgical training must change to protect patients from Tim e Directive is yet to be ap p reciated , how ever, as m any
overly tired physicians and med ical errors. The conse- cou ntries have only recently begu n to im p lem ent these
quences of these externally managed changes m ight not be ru les.
fully apparent for years (9). The limitation of d uty hours
and the resulting increase in information transfer (patient ■ Decreased operative experience of graduating
hand offs), and the possible em ergence of a su rgical w ork-
surgical residents
force w ith a “shift w ork” mentality, may create a d ecrease in
patient satisfaction from fu rther d ilu tion of the p hysician– With the increased bread th of op erative p roced u res to m as-
patient relationship as w ell as in patient safety, as d efined ter d u ring grad u ate m ed ical training, d ecreasing the w ork
by an increase in “near-m isses” or m ed ical errors. The field hou rs in w hich to be exp osed to these p roced u res is inop -
of error analysis has clearly show n that errors occu r in p ortu ne. N ovel solu tions w ill be requ ired . A very practical
system s that are d esigned in a w ay that u nintentionally qu estion is w hether the hou rs off d u ty are hou rs lost from
enables the error. Although resid ents previou sly w ere m astering op erations and p reop erative and p ostop erative
largely responsible for the longitu d inal care of patients, care. Several stu d ies that characterize the tim e and w ork-
this care now occu rs in spu rts and intervals. This care flow of su rgical resid ents have d iscovered a large am ou nt
mod el necessitates frequ ent transfer of encapsulated m ed - of tim e sp ent in noned u cational activities (14). There is a
ical inform ation and sim u ltaneou sly d iscourages ind ivid - large op p ortu nity to stream line and red esign su rgical resi-
ual reassessm ent of the p atient w hen called upon for d ency. “H ou rs w orked ” is a p oor su rrogate for d eterm ining
intervention or ju d gm ent of som e sort. Patient rou nd s now “w ork d one,” and a large fraction of the trad itional d u ties
may serve as occasions in w hich latent errors are enabled . of resid ents need s to be transferred to nonp hysician clini-
A recent survey of su rgeons in training ind icated that cians and ancillary staff, or be offset by m ore efficient m od -
the m ajority felt that they shou ld be allow ed to w ork els of health care d elivery. If it is not accu rate to say that
80 hou rs p er w eek (10). Perhaps this response ind icates resid ents have been the engine of the acad emic health cen-
som e d iscom fort w ith interru p ted continu ity of care and ter, they trad itionally have been the d rivetrain. As resid ents
challenges to p rofessional values. Threshold lim itations of learn to w ork sm arter rather than hard er, hosp itals m ust
w ork hou rs, no m atter w hether they are w ell reasoned or also read ju st.
com pletely arbitrary, u nd ercut the im portance of continu - Althou gh lim itation of d u ty hou rs for su rgical training
ity of care, a p rincip le highly valu ed by su rgeons and one in Sw ed en appears to not have d amaged patient outcomes,
that is absolu tely critical to incu lcate in fu tu re p ractitioners. it has changed the level of experience and the end prod uct
Temp oral restraints have no place in the d efinition of a of su rgical training. A p eriod of ju nior sp ecialist practice
follow s resid ency training to enhance skills, and subspecial- surgery, and vascular surgery (but not thoracic surgery) to
ization is very com m on. Perhaps this factor has preserved create specific curricular tracks, w hich lead to d ual certifica-
excellent patient ou tcom es, but em ergency general su rgery tion in 6 instead of 7 years. In concept, the fourth clinical
operations have suffered because few broad ly trained sur- year serves as a general su rgery chief year and the last
geons rem ain (15). It seems likely that our ow n system 2 years have a concentrated experience in the su bspecialty.
might eventually come to mimic these changes and ad just- Both portions of the program need to take place at a single
ments. Without an accompanying overhaul of the national institu tion, and the p ilot requires both a carefully d efined
(GME) ad ministrative and reimbursement structure and curriculum and specific metrics to d etermine w hether the
lim itations, patient ou tcom es m ay ultim ately su ffer. ESP is a success or failure. The American Board of Thoracic
Another qu estion centers on how to d eterm ine com pe- Su rgery (ABTS) ap proved a similar pilot program in 2001.
tency. The assu m ption inherent in the current mod el of This latter resolution d etermined that certification by the
American su rgical training is that repeated exposure to ABS is op tional and that other pathw ays to ABTS certifica-
patient care and sp ecific operations ensu res com p etency. tion could be d eveloped . Specifically, the Thoracic Surgery
Com p etency is a relative concept, and objective d eterm ina- Directors Association w ould d evelop categorical integrated
tion of p roficiency and com petency rem ains elu sive. H ow 6-year programs for primary certification in Thoracic
many cholecystectom ies are enou gh? Should the goal be to Surgery. While there has been the d evelopm ent of a hand ful
d o as many operations as possible? Can one p erform too of ESP Card iothoracic Surgery programs, these early ESP
many operations before id eal learning no longer occu rs? pilot programs have been largely sup planted w ith the
Shou ld these d efinitions be ind ivid u alized for d ifferent res- d evelopment of primary integrated resid ency programs in
id ents? The overarching qu estion is w hether the grad u at- Vascular and Thoracic Su rgery.
ing resid ent m eeting RRC requ irem ents is tru ly prep ared While these changes are m eant to red efine the training
for ind ep end ent surgical practice, and how d o w e create of vascu lar, p ed iatric, and thoracic su rgeons, the stand ard
metrics by w hich w e can reliably m ake this d eterm ination? cu rricu lu m of the general su rgery resid ency w ill also need
to be rearranged to p rovid e a consistent core exp osu re for
those resid ents w ho track into sp ecialties from an initial
■ Threats to professional values core of general su rgery, w hile red efining the fourth- and
For m any years the natu re of su rgical training w as a para- fifth-year cu rricu la for resid ents rem aining in general su r-
d ox. The fact that surgical training w as so hard , both m en- gery. In ad d ition, for institu tions that have integrated vas-
tally and p hysically pu nishing, so relentless and lengthy, cu lar and card iothoracic resid encies, core exp eriences w ill
w as the thing that m ad e it so u niqu e, so valu able, and so need to be carved out for the General Surgery resid ents as
w orthy. Su rgeons w ere im bued w ith professional valu es w ell. Althou gh m any are concerned abou t the fu rther d is-
such as altru ism and lifetim e learning and continu ou s self- integration of general surgery that this change m ay cause,
im p rovem ent. Most illu strative of this valu e system w as it is conceivable that it cou ld reaffirm general su rgery as a
the continu ity of care, w hich p erm eated su rgical p ractice. d estination instead of an in-transit exp erience. If the final
Su rgeons knew it, patients knew it, and other physicians years are to be preserved as ad vanced experiences in gen-
knew it. As the cu rrent m od el of training involves lim ita- eral su rgery (com p lex hep atobiliary cases, oncology cases,
tion of w ork hou rs and shifts in clinical p ractice tow ard end ocrine p roced u res, etc.), carefu l attention w ill need to
outp atient and short-stay proced u res, su rgical resid ents be p aid to the red esign of the cu rricu lu m requ ired to facili-
are increasingly operating on patients w hom they have not tate the ESPs and integrated resid ency training p rogram s
previou sly m et or evaluated . Sim ilarly, other resid ents and in ord er to preserve exp eriences for those p ursuing a career
facu lty ad d ress com plications w hen they occur. Asid e from in general su rgery. At p resent, ap p roxim ately 85% of gen-
losing the opp ortunity to learn abou t the continuu m of d is- eral surgery trainees are pursuing fellow ship training for
ease and healing, the overall d octor–patient relationship an ad d itional 1 to 2 years to gain exp ertise w ithin a given
becom es comp artm entalized , and as su ch, is likely d im in- field of general su rgery. This is a m essage from our trainees
ished . As care is m ore frequently provid ed in shifts, it w ill that cannot be ignored , and it is u nclear w hether there w ill
be challenging and critically im portant to id entify innova- be op p ortu nities for this tracking and final training to occu r
tive m eans by w hich these p rofessional qu alities can be w ithin the context of general su rgery training in the fu tu re
inculcated into surgical trainees of tod ay and into the or not.
fu ture.
■ Length of training issues
■ HOW WILL SURGICAL TRAINING CHANGE? The trend to su pport earlier specialization and consolid a-
tion of su rgical training cou ld not have com e at a m ore
■ Early specialization programs aw kw ard tim e. The im p act of the 80-hou r w orkw eek on
In 2003, the ABS approved a pilot training scheme called the resid ent ed u cation is not yet com p letely d efined , and the
Early Specialization Program (ESP). This program is meant w orkw eek m ay becom e even m ore constrained in the near
to enable resid ency d irectors in general surgery, ped iatric fu tu re. On the basis of the exp erience in N ew York State
over the last d ecad e, it seem s possible to provid e solid su r- care team w ill be requ ired . N u rse p ractitioners and p hysi-
gical training in the setting of lim ited w ork hours. If the cian assistants have alread y ad d ed su bstantially to both
ESP is to su cceed in the context of lim ited w ork hou rs, the inp atient and ou tp atient settings. Often the cost of these
program d irector p osition w ill becom e even m ore challeng- p ractitioners is borne by the hosp itals that have long bene-
ing. All rotation exp eriences w ill need to be planned and fited from a seem ingly inexhau stible and inexp ensive
provid ed w ith the ed ucation–service balance clearly tip p ed w orkforce in the resid ent p ool. It w ill take carefu l attention
tow ard the form er. by p rogram d irectors and chairm en to d ep loy these ad d i-
It has been su ggested that if su rgical exp erience is tional p rofessionals in d u ties that d ecrease the “service”
meant to stay the sam e, then lim itation of the w eekly w ork expectations of physicians in training w hile increasing the
sched u le w ou ld requ ire ad d itional years of training. This “ed u cation” op p ortu nities. In short, w e have a responsibil-
calculu s is oversim p lified . If our cu rrent fed eral reim bu rse- ity to ensu re that physician extend ers d o not becom e physi-
ment for GME continu es, training extension w ill alm ost cian rep lacem ents. H ow ever, the mod el in w hich physician
certainly not occur becau se of the lim its of the current GME assistants are charged only w ith d ictations and p aperw ork
fu nd ing stru ctu re that d ictates the m axim um term of reim - w hile su rgical resid ents sp end all d ay op erating carries an
bu rsable training to be 5 years. If, how ever, fu rther restric- inherent d anger that w e w ill be breed ing a generation of
tions are p laced on d uty hou rs, ad d itional years of training “incom p lete” su rgeons or “technicians,” w hich w ill even-
are likely to be requ ired as has occu rred in Europ e. Som e tu ally d ecrease ou r resp ect and statu re as a p rofession.
w ould argu e that this has alread y occu rred w ith the p rolif- Incorp oration of these nonp hysician clinicians w ill eventu -
eration of fellow ship s, w hich m any refer to as the “new ally lead to reform s in the inad equ ate p ay and benefit
Chief resid ent year.” stru ctu re of resid ents as the d ifferences in their training
and their level of com m itm ent w ill become m ore evid ent.
■ Novel residency structures and
physician extenders ■ New methods of feedback and assessment
If resid encies cou ld be red esigned to form the id eal training One of the basic prem ises of surgical training is that facts
system w ith u nlim ited financial and p olitical su pport, they m u st be learned . Those resid ents m ost su ccessfu l in surgi-
w ould likely look vastly d ifferent. H ow ever, the im m ed i- cal training are often not those w ith the largest selection of
ately necessary changes m ust be m ad e w ithin the m atrix of facts at the read y bu t those w ho are facile at find ing accu -
cu rrent resou rces and restrictions. A nu m ber of reengineer- rate inform ation w hen know led ge d eficiencies are encou n-
ing solu tions have been su ggested that m anage im m ed iate tered . In resp onse to the grow ing bod y of m ed ical
regu latory issu es w hile variably balancing ed u cational know led ge and p ractical lim its to the cap acity to learn and
need s (15). An Ap prenticeship Mod el is bu ilt arou nd m em orize, technology has fostered robu st and available
sequ ential close w orking relationship s w ith m entor facu lty d ecision su p p ort. Su rgical d ecision m aking increasingly
w ho are chosen for both their skills as teachers and the ed u - u tilizes hand held com p uting and electronic resources for
cational valu e of their p ractice. This m od el theoretically access to the best evid ence for clinical p ractice. Resid ency
minim izes in-hou se tim e on call and resu lts in early inten- p rogram s w ill becom e less focu sed on teaching resid ents
sive technical skills training. The Mastery (Case-Based ) w hat to know and think and m ore on how to find the
Mod el p rop oses that resid ents d evelop know led ge and answ ers they need from tru sted sou rces w hen a gap in
skills associated w ith p red efined d iseases and op erations. their know led ge and exp erience is encou ntered . This
A logistical challenge, this type of p rogram w ould assign ap p roach is a m u ch m ore ap p rop riate and ragogical m od el
cases to resid ents on the basis of ind ivid ual ed u cational for lifelong learning and for the continu al qu est for
need s. This typ e of resid ency w ou ld potentially be m ost im p rovem ent that d efines the su rgical p rofession.
flexible in term s of ad vancem ent, “job-sharing,” and over- The w ays that resid ents and p racticing p hysicians are
all training tim e. Another proposed m od el is based on the evalu ated w ill change su bstantially. Su rgical training has
N ight Float System. This is a m ore trad itional team -based long u sed a m od el of evalu ation that assessed skills glob-
system in w hich som e resid ents p rovid e p atient care only ally and assu m ed transfer of com p etency from one skill set
d u ring the night shift (on a rotating basis). This sched u le to another. The ACGME ou tcom es p roject has alread y
obviou sly is m eant to facilitate m ost of the other resid ents changed this issu e by requ iring a m u ch m ore sp ecific and
going hom e, bu t, ad m itted ly, it su blim ates the ed u cational granu lar w ay of rating com p etency in d efined d om ains.
value of the rotation to the service com ponent. Becau se it is The final form at of the related evaluation instru m ents and
a tem porary and equally d istribu ted experience, it m ight m ethod s is still u nsettled . The level of feed back w ill be
be a legitim ate trad e-off. increased to close the loop betw een ed u cation and assess-
As the p ace of clinical practice increases w ith the aging m ent. One can im agine that the steep slop e of the learning
of the p op u lation and the im p end ing shortage in p hysi- cu rve d u ring su rgical resid ency can be increased even fu r-
cians and as the overall length of training is very unlikely ther by ind ivid u alized , su p p ortive, and sp ecific feed back
to change, it is clear that m any new m em bers of the patient p rovid ed in d efined areas. Com p u ters w ill p rovid e som e of
this feed back d u ring exercises in d ecision analysis and in ■ Simulation training
proced u ral sim u lations.
N o longer w ill su bjective assessm ent of skills, know l- To fu lly d evelop the skills of su rgeons, live patients are
ed ge, and attitu d e be su fficient for evalu ation d u ring resi- absolu tely necessary. Of cou rse, there is an obligation to
d ency training. Com petency w ill be d efined by m easu rable p rovid e optim al treatm ent and ensure patient safety and
criteria, and these d ata w ill be u sed for d ecisions regard ing best ou tcom es. Balancing these tw o need s rep resents a fun-
grad ed responsibility and for p rom otions and ad vance- d am ental ethical tension in su rgical ed u cation (17). Other
ment throu gh the training schem es. If these strategies are p rofessions that are typified by long stretches of rou tine
ad equ ately op erationalized , resid encies m ight eventu ally shattered infrequ ently by high-hazard , high-acu ity crises,
be comp etency-d riven (and relatively tim e-ind ep end ent) su ch as the aviation ind u stry, the m ilitary, and the nu clear
instead of tim e-d riven (and relatively com petency- p ow er ind u stry, have long ago institu tionalized sim u la-
ind ep end ent). For this change to occu r, the rigid lim itations tion-based training. Med ical ed u cation has been slow to
of GME fu nd ing need to be red esigned significantly. Im p le- em brace sim u lation for reasons of cost, com placency, and
mentation w ill ultim ately require accurately d efining the lack of rigorou s d eterm ination of reliability and constru ct
key elem ents of surgical training, establishing qu antifiable valid ity. Focu sed by the p atient safety m ovem ent, the face
metrics, stringently m easu ring perform ance against crite- valid ity of sim u lation ed u cation is overw helm ing. Many
ria, and rep orting ou tcom es throu ghout the career of a recent articles in the ethics literature have cond em ned the
surgeon (15). u se of sed ated or d ying patients for training in exam ina-
tions or basic p roced u res, again highlighting the role for
sim u lation-based training (18).
■ Educational integration The first attem p ted su rgical sim u lations u tilizing vir-
A shift in w here and by w hom resid ents are trained w ill tu al reality took p lace a d ecad e ago. Since then, com pu ter
likely occu r. There is very likely to be a shortage of qu ali- p ow er has rap id ly im p roved , as has the qu ality of proce-
fied p hysicians in the years to com e (16). It is p robable d u ral sim u lation both in term s of visu al fid elity and
that the total nu m ber of slots for training w ill increase, enhancem ents su ch as hap tic feed back. The d igital aspect
and these w ill m ost likely be increm ental ad d itions at of these com p u ter-based sim u lations allow s robust d ata
larger, better-coord inated p rogram s. This w ill requ ire, cap tu re to p rovid e im m ed iate p erform ance assessm ent and
how ever, concessions m ad e in the Balanced Bu d get Act of feed back. Althou gh the literatu re establishing the construct
1997 w hich has cu rrently cap p ed the total nu m ber of valid ity and the reliability of these ed u cation and assess-
trainees in a given institu tion at the level p resent in 1997. m ent tools is relatively lim ited , it is grow ing exp onentially.
As the com p lexity of the su rgical field and the p revalence Professional organizations have begun to seriou sly con-
of su bsp ecialty p ractice increases, and resid ents increas- sid er the potential of these tools to revolu tionize the surgi-
ingly p u rsu e fellow ship training, it is inevitable that the cal training and certification p rocesses, and at p resent all
op erative exp erience of fellow s w ill com p ete w ith that of surgery training program s are requ ired by the ACGME to
resid ents. Su ccessfu l m anagem ent of this com p etition w ill have access to som e level of sim u lation for general su rgery
requ ire an increase in the coord ination that occu rs w ithin training (19,20).
and betw een training p rogram s, esp ecially in light of the Although the ad vent and d iffu sion of laparoscopic su r-
cu rricu lar im p lications of the ESPs and p rim ary su bsp e- gery w as soon follow ed by cu rricu la and gu id elines for
cialty integrated p rogram s. For exam p le, p rogram s w ith training, the sp ecific m etrics of evalu ation w ere lacking.
an active vascu lar su rgery fellow ship or resid ency m ight Ow ing to efforts in such d iverse locations as Scotland ,
choose to have general su rgery resid ents rotate at active Canad a, and the United States, sop histicated analyses of
sites w here the vascu lar su rgery fellow or resid ent d o not p sychom otor skills have led to objective structured assess-
rotate. m ents for technical skills. Cu rrently, there is no stand ard -
Another aspect of educational coordination w ill involve ized threshold level that resid ents are exp ected to attain,
taking full ad vantage of scientific and clinical expertise, and there is no consensu s on m etrics of p erform ance, m eth-
w here and w hen it exists. Distance learning via the Internet od s of evalu ation, or the significance of these m easu re-
and live telesurgery transmissions make this a very tangible m ents w hen ap p lied to clinical ou tcom es (20,21). This
possibility. As the body of surgical knowledge increases, and exp erience in teaching stand ard su rgical skills has not been
as the multidisciplinary aspect of clinical care becomes more fu lly realized in su rgical sim u lation technology. For a cu r-
prominent, better coordination betw een undergraduate, ricu lu m based on accep ted criteria in the training and eval-
grad uate, and continuing med ical curricula w ill need to be u ation of technical skills on a sim u lator, Satava has
defined . Because the ad vanced technology aspects of surgi- recom m end ed the follow ing steps: (i) d evelopm ent of stan-
cal practice impact the spectrum of caregivers, the ed uca- d ard ized d efinitions/ taxonom y of technical skills (e.g.,
tional process w ill often involve teams. Because of patient- m etrics); (ii) d efinitions/ taxonom y of errors; (iii) establish-
safety issues, the costs of this ed ucation w ill likely be shifted m ent of core ou tcom es/ resu lts rep orting; and (iv) d evelop -
to hospitals. m ent of a com p rehensive cu rricu lu m . The curriculum
FIGURE 3.1. Simulators are avail-

able for many procedures.
should inclu d e (i) d id actic inform ation (lecture, m u ltim e- and others (Fig. 3.1). For m ost of these ap p lications, the
d ia, etc.) of the relevant anatom y and correct p erform ance p roced u re being sim u lated requ ires interaction w ith an
of the skills being tau ght; (ii) d efinition and d escrip tion of im age. The im age serves as the basis for the sim u lation. For
the errors the sim u lator w ill d etect; (iii) p retest d ocu m enta- that reason, simu lation of op en op erations, w here the inter-
tion that the stu d ent u nd erstand s the inform ation; (iv) p er- action w ith tissu e u ses m any senses, is years aw ay—or per-
form ance of the simu lation w ith im m ed iate feed back after hap s u nattainable. As im p ressive as som e of the cu rrently
errors; (v) a final report on perform ance; and (vi) a longitu- available sim u lators are, it is fascinating to consid er that
d inal record of the perform ances over tim e as w ell as com - the field is generally at the sam e stage of d evelop m ent as
parison to p eer levels (21). the first flight sim u lator (20). It took nearly 20 years for the
Cu rrently, simu lation-based training and assessm ent field of flight sim u lation to d evelop into a stand ard part of
is available for su ch d iverse proced ures as general flight training and certification, so w e w ill likely continu e
laparoscop y, lap aroscopic cholecystectom y, hysteroscop y, to see significant ad vances in su rgical sim u lation. In ad d i-
bronchoscop y, esop hagod uod enoscop y, end oscop ic retro- tion, the ability to sim u late interactive environments w ith
grad e cholangiop ancreatography, end oscop ic u ltrasou nd , technologies su ch as the CAVE (Cave Au tom atic Virtu al
arthroscopy, endoscopic sinus surgery, endovascular surgery, Environm ent) (Fig. 3.2) and the geow all stereoscopic
FIGURE 3.2. Simulated environ-

ments may be important to increase
the fidelity (sense of realism) when
interacting with simulated patients
or procedures. Interactive virtual
reality environments such as the
operating room (left panel) can be
projected into the CAVE (Cave Auto-
matic Virtual Environment) environ-
ment (right panel) to create an
immersive virtual environment.
projection system w ill have the potential to increase fid elity 7. Inglehart JK. Med icare’s d eclining p aym ents to p hysicians. N Engl J
Med 2001;346:1924–1930.
and to enhance evalu ation of p erform ance und er stress. 8. Lu d m erer KM. A time to heal. N ew York: Oxford University Press; 1999.
9. Ru ssell RCG. Lim itations of w ork hou rs: the U.K. exp erience. Surgery
2003;134:19–22.
■ CONCLUSION 10. Und erw ood W, Boyd AJ, Fletcher KE, The Execu tive Com m ittee of the
Am erican College of Su rgeons-Cand id ate Associate Grou p , Lyp son
ML. View p oints from generation X. A su rvey of cand id ate and associ-
Change is upon u s and the opportunities are num erous to ate view points on resid ent d u ty-hou r regu lations. J Am Coll Surg 2004;
fu rther im prove the system of su rgical training in the 198:989–993.
United States. We m ust now be p roactive in ord er to 11. Fischer JE. Continu ity of care: a casu alty of the 80-hou r w ork w eek.
Acad Med 2004;79:381–383.
im prove the field and enhance the aspects of surgery that 12. Rom anchu k K. The effect of lim iting resid ents’ w ork hou rs on their
w e cherish. As characterized by an im provem ent in the surgical training: a Canad ian p ersp ective. Acad Med 2004;79:384–385.
ratio of resid ent ed u cation to resid ent service and the incor- 13. Ihse I, H aglu nd U. The Sw ed ish 40-hou r w orkw eek: how d oes it affect
surgical care? Surgery 2003;134:17–18.
poration of p hysician extend ers into the clinical enterp rise, 14. Brasel KJ, Pierre AL, Weigelt JA. Resid ent w ork hou rs. What they are
and as enhanced by com p uter-based learning and sim u la- really d oing. Arch Surg 2004;139:490–494.
tion, the fu tu re of su rgical training is qu ite bright. 15. DaRosa DA, Bell RH , Du nnington GL. Resid ency p rogram m od els,
im p lications, and evalu ation: resu lts of a think tank consortiu m on res-
id ent w ork hou rs. Surgery 2003;133:13–23.
16. Coop er RA, Getzen TE, McKee JH , et al. Econom ic and d em ograp hic
■ REFERENCES trend s signal an im p end ing p hysician shortage. Health Aff 2002;21:
140–154.
1. Zelenock GB. Presid ential ad d ress: m ed ical ed u cation: thou ghts on the 17. Ziv A, Wolp e PR, Sm all SD, et al. Sim u lation-based m ed ical ed u cation:
training of p hysicians and su rgeons. J Vasc Surg 2003;37:921–929. an ethical im p erative. Acad Med 2003;78:783–788.
2. Ru ssell TR. What is the fu tu re of su rgery? Arch Surg 2003;138:825–831. 18. Rosenson J, Tabas JA, Patterson P. Teaching invasive p roced u res to
3. Mulholland MW. Program increases m ed ical stu d ent interest in su rgi- m ed ical stu d ents. JAMA 2004;291:119–120.
cal careers. Bull Am Coll Surg 2003;88:25–27. 19. Seym ou r N E, Gallagher AG, Rom a SA, et al. Virtu al reality training
4. Kohn L, Corrigan J, Donald son ME. To err is human: building a safer im proves operating room p erform ance. Ann Surg 2002;236:458–464.
health system. Washington, DC: N ational Acad em ic Press; 2000. 20. Satava RM. Accom p lishm ents and challenges of su rgical sim u lation.
5. Ulm er C, Wolm an D, Johns M. Resident duty hours: enhancing sleep, Daw ning of the next-generation su rgical ed u cation. Surg Endosc 2001;
supervision, and safety. Washington, DC: N ational Acad em ic Press; 2009. 15:232–241.
6. Kassirer JP. Acad em ic m ed ical centers u nd er siege. N Engl J Med 1994; 21. Satava RM. Disru ptive visions. Su rgical ed u cation. Surg Endosc 2004;
331:1370–1371. 18:779–781.
CHAPTER
4
Continuing Education for
Practicing Surgeons
Richard E. Burney and R. Van Harrison
Continuing medical education (CME) consists of educational activities. Physicians p articip ating in these activities are
activities that serve to maintain, develop, or increase the knowl- aw ard ed this cred it. Variou s state and local ad m inistrative
edge, skills, and professional performance and relationships that a entities m and ate that physicians obtain this form al cred it
physician uses to provide services to patients, the public, or the for relicensu re and other regu latory requ irements. CME
profession. The content of CME is the body of knowledge and m ay also be m and ated as a requ irem ent for cred entialing
skills generally recognized and accepted by the profession as w ithin a hosp ital or health care organization. The prim ary
within the basic medical sciences, the discipline of clinical medi- p u rp ose for seeking continu ing ed u cation is to im prove
cine, and the provision of health care to the public (1). p atient care, not to satisfy licensing and other m and ates,
In the broad est sense, CME for su rgeons is the acqu isi- bu t the latter p rovid es incentive for p articip ating in CME
tion of new know led ge and skills after com pleting resi- activities. For those m otivated to learn, the accu m u lation of
d ency or fellow ship training. Once beyond the stru ctu red CME cred its presents less of a problem than d oes the
environm ent of p ostgrad uate training, all su rgeons face the p rop er record ing and d ocu m entation of that CME for
ongoing challenge of m aintaining their general m ed ical ad m inistrative and rep orting p u rp oses.
know led ge base, keeping u p w ith changes in basic p atho-
p hysiology of d isease, learning about new pharm acothera-
p eutic agents, becom ing acquainted w ith new or im p roved ■ BRIEF HISTORY OF CME
surgical techniqu es, im proving d ay-to-d ay m ed ical and
surgical care p ractices, acquiring new technical skills, and At the tu rn of the 20th centu ry, on Ju ly 3, 1900, Sir William
learning how to u se new d evices and ap p ly new technol- Osler gave an ad d ress in Lond on entitled “The Im portance
ogy in their d aily lives. Physicians tod ay also need to learn of Post-Grad u ate Stu d y,” in w hich he em p hasized the
how to p u t new m ed ical know led ge and new asp ects of im p ortance of lifelong learning for p rofessional com p e-
surgical care into p ractice in collaboration w ith other tence. This event is generally accep ted as the birth of CME
health care team m em bers, w ithin their health care sys- (3). Since then the im p ortance of ad vancing the p rofession
tem s, consistent w ith national health care policies. All these by p rovid ing opportu nities for ind ivid u al p ractitioners to
things are part of CME and continu ed professional d evel- acqu ire new inform ation and im p rove skills has never been
opm ent (also referred to as “life-long learning”). Contin- qu estioned . The Am erican College of Su rgeons (ACS) w as
u ed learning is a p rerequisite to good practice and to the fou nd ed in 1913 to d evelop , am ong other goals, a broad
p revention of com plications that can occu r w hen ed ucation and continu ing p rogram for p ostgrad u ate su rgical ed u ca-
or p ractices are d eficient. Su rgeons have a professional tion. One of the chief p u rp oses of m ed ical societies, surgi-
obligation to continu e their ed u cation and to m aintain cal associations, and sp ecialty societies has been to sponsor
com petence throu ghout their surgical careers (2). journals in w hich to p ublish and d issem inate new inform a-
A narrow er view of CME is that it is the enterp rise over- tion. University-based p ostgrad u ate cou rses w ere d evel-
seen by the Accred itation Cou ncil for Continuing Med ical op ed in the 1930s. In the p ast 50 years, acad em ic m ed ical
Ed u cation (ACCME). The ACCME’s m ission is to id entify, centers and m ed ical and su rgical sp ecialty organizations
d evelop , and p rom ote stand ard s for quality of CME. have p layed increasingly larger roles in p rovid ing continu -
ACCME accred its eligible institu tions by review ing the ing ed u cation p rogram s that offer learning op p ortu nities
p rocesses that CME provid ers follow in d eveloping and for p racticing p hysicians. More recently, sp ecialty societies
p rod u cing CME activities. Accred ited CME provid ers can and d evice m anu factu rers have sp onsored cou rses to assist
d esignate Am erican Med ical Association Physician Recog- su rgeons to learn how to u se new technologies, su ch as
nition Aw ard (AMA-PRA) Category 1 Cred it TM for their u ltrasou nd , lap aroscop ic and robotic su rgery.
In the early 1970s, several trend s m ad e CME a focu s of
ad d itional attention. First, the expansion of scientific infor-
mation mad e med ical practice more com plex w hile offering
Richard E. Burney, R. Van Harrison: University of hope for cure of previously untreatable med ical problems.
Michigan, Ann Arbor, MI 48109. Second , patients and their ad vocates began to call attention
22
Chapter 4 • Continuing Education for Practicing Surgeons 23
to errors and failu res in m ed ical practice, and the costs Table 4 .1 Rea d ily ava ila ble sou rces of
associated w ith m ed ical m alpractice actions began to rise con t in u in g m ed ica l ed u ca t ion (CM E)
and be recognized as a major societal problem . Third , ed u -
cational psychologists began to d efine and analyze ad u lt Informal discussion or consultation with colleagues
ed ucational processes m ore scientifically and to id entify Textbooks and journals
those that are m ost effective. Finally, the Am erican Med ical Reading only
Association, in response to these p ressu res and m aking the Reading CME quiz
assu m p tion that lack of inform ation w as a rem ed iable Hospital/Intramural conferences and committees
cau se of p hysician failu re, prop osed that physicians volu n- Teaching conferences
tarily obtain 50 hou rs of CME per year in ord er to m aintain Morbidity and mortality conferences
proficiency. Physicians w ho d id so becam e eligible for the Multidisciplinary committees (e.g., Tumor Board)
PRA from the AMA. Journal club
Another response to these pressu res w as the introd u c- Quality assurance/quality improvement committees
tion of new regu lations by state governm ents. By 1978, 13 Computer- (CD/DVD) and Internet-based educational programs
states, beginning w ith N ew Mexico and Michigan, had Hospital/medical school sponsored
passed law s that m ad e 50 hours p er year of CME m and a- Specialty society-provided (e.g., Society of Colon and Rectal Surgeons)
tory for relicensu re. Most other states have p assed sim ilar Industry-sponsored and commercial sites
law s—cu rrently 44 states requ ire CME for relicensu re (4). Professional meetings
This new, m and atory CME requirem ent led to an exp an- Surgical association meetings (e.g., American College of Surgeons)
sion of entrep reneu rial CME offerings. Tim e and m oney Clinical Congress
w ere sw iftly invested in p rovid ing ed u cation op p ortu nities Postgraduate courses
for p hysicians, som etim es in vacation settings and often of Regional meetings
qu estionable p ractical or ed u cational value. At the sam e Special certification courses (e.g., Advanced Trauma Life Support)
tim e, m and atory CME had the salutary effect of encou rag- Specialty society meetings
ing hospitals to d evote fu nd s and attention to provid ing University-sponsored postgraduate courses
CME for m ed ical staff m em bers. Skills/Technology acquisition courses (with or without commercial
funding)
■ SOURCES AND CHARACTERISTICS OF University-based (e.g., sentinel node biopsy)
Professional society-based (e.g., ultrasound)
HIGH-QUALITY, EFFECTIVE CME Industry-sponsored (e.g., advanced laparoscopy)
Diffu sion and acqu isition of new know led ge occu r throu gh Simulation centers
a variety of m echanism s and stim uli, both form al and
inform al. A list of the m ost com m on, read ily available
sou rces of continu ing ed ucation is show n in Table 4.1. Only
a sm all nu m ber of these are form al CME offerings. The and ind u stry facilitate the skill acqu isition need ed to app ly
most com m on and frequ ently unacknow led ged source of new know led ge.
new inform ation is inform al d iscussion w ith professional
colleagu es. Most su rgeons obtain new inform ation by ask-
ing qu estions of their m ed ical and surgical colleagu es. In ■ PRINCIPLES OF ADULT EDUCATION
the right circu m stance, this is one of the chief sou rces of AND LEARNING
reliable, p ractical inform ation.
An u nd erstand ing of how ad u lts learn w ill help one select
Regu lar gathering of general inform ation through read -
a balance of learning activities that w ill be m ost efficient
ing of relevant jou rnals and reports is a sim ple yet basic
and effective. A nu m ber of m od els have been d eveloped
w ay to exp and one’s know led ge base. Every surgeon m u st
for the com p lex p rocesses involved in learning (5). Most
set asid e tim e to read a selection of jou rnals and other
ed u cation m od els su ggest at least fou r p rerequ isites for
sou rces of w ritten inform ation. Com pu ter- and Internet-
effective continu ing ed u cation and learning to occu r.
based ed u cational m aterials are proliferating and are read -
ily available from a variety of sources, as w ell. ■ Motivation: The first and m ost im p ortant p rerequisite is
Also im portant is attend ing a selection of local, the intrinsic m otivation to qu estion oneself, to learn, and
regional, or national p rofessional m eetings at w hich a to im p rove. The stu d ent w ho has a qu estion to be
broad range of inform ation is offered and at w hich one can answ ered , or is aw are of a d eficiency or an inad equ acy in
share inform ation w ith colleagu es and ask qu estions. need of correction, w ill have a strong m otivation to learn
Becom ing aw are of new know led ge ind u ces one to ask or change behavior. Dilem m as and qu estions encoun-
qu estions that lead to m ore d irected or focu sed learning tered in d aily practice are prim e sou rces of m otivation,
and is the first step tow ard the ap plication of this new bu t not the only ones. Com p etitive p ressures and
know led ge into practice. H igh-qu ality skill acqu isition changes in services arising from strategic p lanning can
cou rses offered throu gh u niversities, professional societies, also be motivating.
■ Objective: The stu d ent m u st have a clear goal or objec- ior. N ew p ain-m anagem ent ap p roaches and techniques
tive in m ind for ap p lying that new know led ge or skill, have been available for over a d ecad e, bu t su rgeons are
i.e., know how and w hen the new inform ation w ill be only now slow ly accep ting them .
put to u se. ■ Adoption: H aving agreed that new inform ation is valid ,
■ Practice: The stu d ent m u st have the op p ortu nity not ind ivid u als m u st d ecid e to ad op t that inform ation into
only to read and hear abou t w hat is to be learned bu t also their p ractices. Ad op ting a new id ea m ight requ ire m ak-
to ap p ly or p ractice the new behavior in an ap p rop riate ing changes in d ay-to-d ay p ractices and in the related
sim u lation context or environm ent, both to gain fam il- p ractices of those around them .
iarity w ith it and to gain insight into it. ■ Adherence: The cycle of learning is com p lete w hen ind i-
■ Application and feedback: Finally, the stu d ent m u st vid u als regu larly ap p ly the changes in p ractice, exam ine
app ly the new behavior or p ractice it promp tly on a reg- the ou tcomes over tim e, and m ake m od ifications that
ular basis and there m ust be tim ely evaluation or feed - im p rove p ractice.
back, throu gh d ata collection and analysis of ou tcom es,
Table 4.2 d isp lays fou r typ es of continu ing ed u cation
on its su ccess or failu re.
activity in the form of a continu u m , the level of p ersonal
For an ind ivid u al, the phases of learning that bring engagem ent requ ired for each, how each relates to the gen-
about behavioral change m ay be sum m arized as aw are- eral p rerequisites for ad u lt learning and to the ind ivid u al
ness, agreem ent, ad option, and ad herence (6). p hases of learning ou tlined above, and som e of the ad van-
tages and d isad vantages of each. The typ es of CME activity
■ Awareness: Ind ivid u als becom e aw are of new id eas
m ay be su m m arized as follow s:
throu gh read ing, brow sing Internet sites, attend ing
meetings, d iscu ssing m atters w ith colleagu es, and con- ■ General awareness: A su rgeon ’s in trinsic m otivation
fronting clinical d ilem m as on a d aily basis. to increase kn ow led ge lead s to scan nin g jou rn als and
■ Agreement: Ind ivid u als m ust intellectually agree that attend ing w eekly lectu res, annu al u p d ate p rogram s,
new inform ation is approp riate and w orthw hile. Som e- and general review cou rses. These p assive activities
tim es new and im p ortant inform ation is not accep ted are im p ortant in p rovid ing an aw areness of new
rapid ly, p articu larly w hen it calls for a change in behav- kn ow led ge bu t are th e least likely to brin g insigh t in to
Table 4 .2 Typ es of CM E a ct ivit ies a n d t h eir ch a r a ct er ist ics

General Prerequisites Phases of Individual
Type of Activity Level of Engagement for Learning Learning Advantages and Limitations
General Awareness
General reading Passive learning Motivation Awareness Broad content covered
Informal discussion Unfocused Introduces unknown issues
Listening at conference Limited expense
Viewing a video Limited likelihood of producing
change by itself
Answering Questions
Consultation with colleague Active learning Motivation Awareness Focus on practical issues
Literature search More focused Objective Agreement Must be aware of issue already
Problem-based learning Limited expense
activities Somewhat likely to produce change
Interaction with others
Skill Training
Preparation and interaction Interactive learning Motivation Awareness Focus on priority skills
Role playing or simulation Skill acquisition Objective Agreement Often meaningful
Skill practice/demonstration Practice Adoption Likely to produce specific change
Testing/evaluation May carry high direct or indirect expense
Performance Review
Regular data collection, Participation in research Motivation Awareness Focus on specific activities
analysis, and evaluation or clinical trial Objective Agreement Often requires supporting infrastructure
Regular feedback regarding Organized change Practice Adoption and related expense
performance or outcome initiative Application and Adherence Very likely to produce specific change
Prompt application of change feedback
or skill into daily practice
with feedback
cu rrent p roblem s or by them selves to ind u ce change in of CME result in changes in competence (ability to imple-
behavior. ment), performance, and / or patient outcomes (7). CME is
■ Answering questions: Settings that d emand active par- expected to also foster particip ation in system s-based p rac-
ticip ation, p resentation, d iscu ssion, or argum ent help tice and practice-based learning. CME should support prac-
the su rgeon d eterm ine the u sefu lness of new inform a- tice improvement, w hich is part of new requirements for
tion and d ecid e w hether to accept it. Active particip ation recertification (see next section), evolving Joint Com m ission
inclu d es d irected read ing or a literatu re search d esigned on Accred itation of H ealthcare Organizations (JCAH O)
to answ er sp ecific qu estions. requirem ents, and national qu ality im provem ent efforts to
■ Skill training: H aving a specific goal and participating in id entify and ad d ress perform ance “gap s.”
a course that offers a setting for learning and practice Fu tu re high qu ality CME activities w ill increasingly
under expert monitoring and assistance provide excellent balance tw o typ es of know led ge: (1) inform ation abou t
in-depth learning, including practice and adoption of new new biom ed ical p rocesses and treatm ents and (2) inform a-
skills. H ighly successful postgrad uate courses, such as the tion abou t how to translate that biom ed ical know led ge
ACS Advanced Trauma Life Support course, embody the into p ractice. The “translation” p rocess requ ires consid era-
characteristics of active learning and participation by tion of barriers and facilitating factors affecting p atients,
motivated participants. Courses that teach new surgical other m em bers of the health care team , and the institu -
techniques, such as laparoscopic and robotic surgery, are tional setting.
also commonly available. Simulation centers now assist Su rgeons w ho p lan, p articip ate in and / or attend CME
physicians to acquire specific new skills as well. activities are going to be asked to enhance the “transla-
■ Performance review: Review s of practice throu gh m ortional” content of those activities. Did actic sessions that
bid ity and m ortality conferences, exam ination of com p li- typ ically begin w ith the p resentation of new m ethod s of
cation rates, p ersonal d atabases, or case logs that record care and evid ence for those m ethod s w ill need to go
ou tcom es, and other m ethod s of feed back help assu re beyond that content. Ways to im p lem ent those m ethod s
ongoing im p rovem ent in p ractice. shou ld also be introd u ced and d iscu ssed , i.e., translate the
changes in know led ge into op erationally im p roving
An organized p lan for continu ing ed u cation and p ro-
p atient care. Attention shou ld be given to changes need ed
fessional d evelop m ent m u st have a balance across the var-
in the care environm ent (the “system ” of care, e.g., p eople,
iou s typ es of CME activities. Tim e, location, and
p rocesses, p hysical arrangem ents) that w ill facilitate su c-
p racticality d em and that m u ch CME tim e w ill be d evoted
cessfu l im p lem entation. The session shou ld conclu d e by
to broad , inform ation-gathering activities, su ch as scan-
helping participants form u late plans for taking the next
ning for new inform ation in d iscu ssions, read ing, confer-
step s need ed to bring abou t d esired changes. These
ences, and regu lar m eetings. In so d oing, one continu ou sly
requ irem ents are consistent w ith the p rim ary p u rp ose for
gathers inform ation that is p otentially ap p licable to all
seeking continu ing ed u cation, w hich is to im prove actual
asp ects of one’s su rgical p ractice. This broad er inform a-
p atient care.
tion gathering help s id entify gap s in know led ge and m oti-
vates in-d ep th stu d y of a few areas each year. Skill
acqu isition cou rses, althou gh highly effective, are exp en-
sive, tim e consu m ing, and resou rce intensive. They shou ld ■ PREPARING FOR RECERTIFICATION AND
be carefu lly selected to fill in know n gap s or to im p rove RECREDENTIALING REQUIREMENTS
clinical p ractice in w hich a scan of the environm ent su g-
Pu blic d em and for m ore evid ence of com petence in prac-
gests it is d eficient. Only a lim ited am ou nt of tim e and
tice has led to new professional efforts to d evelop broad er,
resou rces can be d evoted to these, and they shou ld , there-
m ore reliable, rep rod u cible m ethod s to d em onstrate clini-
fore, fit carefu lly into one’s overall p lan for p rofessional
cal com p etence and ap p rop riate p erform ance. The Am eri-
d evelop m ent. Ord inarily, one can learn, ad op t, im p le-
can Board of Med ical Sp ecialties (ABMS) in 1999 ad opted a
m ent, and evalu ate new skills only one at a tim e. Id eally, at
new d escrip tion of the “com p etent p hysician.” The general
the end of each year, one shou ld be able to record the
com p etencies d efined by the ABMS are
learned item s that have im p roved one’s clinical p ractices
and p atient care. ■ m ed ical know led ge
■ p atient care
■ interp ersonal and com m u nication skills
■ TRANSLATING KNOWLEDGE INTO PRACTICE ■ p rofessionalism
■ p ractice-based learning and im provem ent
Social and financial pressures on the U.S. health care system
■ system s-based practice.
have increased expectations for CME—not sim p ly to instill
new biom ed ical know led ge bu t also to facilitate the im ple- As a fu nctional com p lement to this new d efinition, the
mentation of that know led ge into practice. In 2006 the ABMS ad op ted in Sep tem ber 2002 a new p rogram for
ACCME ad opted new criteria for accred itation that require “maintenance of certification” (8,9). The fou r com ponents
CME p rovid ers to d emonstrate that overall their p rogram s of this p rogram are
■ evid ence of p rofessional stand ing ing Initiative (http :/ / w w w.cm s.hhs.gov/ p qri) and the
■ evidence of commitment to life-long learning and involve- Su rgical Care Im p rovem ent Project, that encou rage p er-
ment in period ic self-assessm ent form ance review (13). The Am erican College of Su rgeons
■ evid ence of cognitive expertise has established an on-line case rep ort system to facilitate
■ evid ence of evaluation of perform ance in practice. record ing of su rgical activity and ou tcomes analysis by
ind ivid u al su rgeons (14).
In ad d ition to the cu rrent requ irem ents for evid ence of In the 10-year recertification cycle, su rgeons m ust sub-
CME and of su ccessfu l com p letion of a test of p ractice- m it every three years evid ence of good p rofessional stand -
related know led ge, the ABMS requ ires that the ap p licant ing, annu al p articip ation in CME, and p articip ation in a
hold an u nrestricted license to p ractice and p articip ates in p rogram in w hich they evalu ate their p erform ance. Every
p erform ance evalu ation and self-assessm ent. Physicians 10 years they m u st take a secu re ABS w ritten exam ination
are asked to d em onstrate that they can assess the qu ality in their sp ecialty. The content for the w ritten exam ination
of care they p rovid e com p ared to p eers and national can be fou nd p rim arily in stand ard textbooks and recent
benchm arks and then ap p ly the best evid ence or consensu rgical literatu re.
su s recom m end ations to im p rove that care u sing follow -
u p assessm ents. The ABMS is com p leting a several-year
transition as ind ivid u al certifying board s and sp ecialty
■ INDUSTRY, ETHICS, AND CME
societies d evelop and m ake available the necessary The availability of ind u stry-su pported and d irected CME
resou rces that w ill enable p hysicians to d em onstrate these op p ortu nities and the ind u cem ents to p articip ate in such
com p etencies. activities m ight m ake it d ifficu lt for p hysicians to avoid
Since 1976, all su rgeons certified by the Am erican Board crossing the threshold of ethical behavior. The offering of
of Surgery (ABS) have had to recertify every 10 years to gifts and ind u cem ents to m od ify behavior is an ancient and
m aintain their certificate. Beginning July 1, 2005, ABS p ow erfu l tool for influ encing others. Su rgeons shou ld seek
d ip lom ates w ho w ish to certify or recertify in any sp ecialty the inform ation and training that w ill best serve their
m ust p articip ate in the ABS Maintenance of Certification p atients. Su bsid ies and ind u cem ents can cau se a surgeon to
(MOC) Program (10,11). The ABS MOC program is based choose a convenient CME activity instead of one w ith m ore
d irectly on the com p onents id entified by the ABMS: evi- im p ortant content. If a su rgeon accep ts a free trip to learn
d ence of cu rrent good p rofessional stand ing, evid ence of to u se a p iece of equ ip m ent or learn a new techniqu e,
CME, su ccessfu l p erform ance on a w ritten exam ination, that surgeon w ill feel a sense of obligation to a person or
and evalu ation of perform ance in practice through u se com p any.
of ou tcom e m easu res and qu ality im p rovem ent p rogram In the p u rsu it of new skills, su rgeons m u st be cognizant
particip ation. of p otential ethical issu es and conflicts of interest.
Good professional stand ing can be verified by m ain- Ad vances in surgical techniqu e require acqu isition of new
taining an unrestricted m ed ical license and hospital privi- equ ip m ent and learning new technical skills. Coop eration
leges and by su bm ission of hosp ital references. The CME w ith sales representatives and m anufacturers after pu rchas-
requirem ent is 50 hou rs (at least 30 hou rs AMA PRA Cate- ing d ecisions have been m ad e is essential for learning how
gory 1 Cred it TM ) annu ally, w ith one-third of Category 1 to u se new tools and equ ip m ent safely. Pu rchase agree-
CME to inclu d e self-assessm ent activity (11). For exam p le, m ents might inclu d e the cost of su ch training. It is inappro-
the ACS offers the Surgical Ed u cation and Self-Assessm ent p riate, how ever, to accep t d irect p ersonal benefits, su ch as
Program (SESAP). The SESAP is an ed u cational program to m oney, food , or lod ging, p rovid ed by salesp ersons or
help su rgeons m aintain cu rrent know led ge in clinical su r- d evice m anu factu rers as p art of CME p rogram s that are
gery and is promoted as a stu d y guid e for the ABS certifica- p rim arily d esigned to encourage surgeons to purchase or
tion and recertification exam s (12). Com pletion of SESAP u se their equ ip m ent. Su ch p articip ation is u nethical
provid es 60 hou rs Category 1 Cred it. becau se the ind ucem ents of personal benefits to the sur-
Surgeons can evalu ate their “perform ance in practice” geon conflict w ith the su rgeon’s im p artiality in selecting
by particip ating in a national, regional, or local su rgical learning activities and equ ip m ent that best m eet the need s
ou tcom es d atabase or qu ality assessment program . One of p atients.
w ay to d o this, for exam ple, is to use the ACS Case Log sys- A p rofessional relationship betw een m ed ical p rofes-
tem , w hich the ACS initiated to help su rgeons d evelop a sionals and com m ercial rep resentatives that avoid s accept-
personal learning p ortfolio that links personal practice d ata ing gifts, ind u cem ents, p rod u ct end orsem ents, or other
to that of others. The ACS Case Log m eets MOC requ ire- form s of com m ercial co-op tion can and m u st be m ain-
ments for the ABS (http:/ / acscaselogregister.org/ ). The ABS tained at all tim es. This d oes not inhibit m anu factu rers
provid es lists of Practice Assessm ent Resources and Self from ad vertising or financially su p p orting ind ep end ent
Assessm ent Resou rces on its w eb site (http:// hom e. ed u cational activities. Manu factu rers m ay ethically su p-
absurgery.org/ ). The Center for Med icare and Med icaid p ort CME p rogram s that are volu ntary and op en to all, d o
Services of the Departm ent of H ealth and H u m an Services not bias p rogram content, and contain no ind ivid ual
has introd u ced tw o program s, the Patient Qu ality Rep ort- ind u cem ents. In 2009, com m ercial fu nd ing and exhibit fees
provid ed 52% of the financial revenu e for the 709 national actual outcomes and hold them up against relevant bench-
provid ers of CME accred ited by ACCME (15). To help su r- marks. Recred entialing and recertification requirem ents are
geons avoid unethical behavior in pu rsu it of new skills making this kind of exam ination of personal performance
and techniqu es, the ACS has p rom ulgated stand ard s for mand atory. Professional societies are d eveloping new learn-
ad vanced cou rses in new technologies and also gu id elines ing tools and Internet-based programs by w hich they hope
for collaboration of ind ustry and su rgical organizations in to facilitate this process. Maintaining a learning program
sup p ort of research and continu ing ed u cation (16,17). that combines both previously available and emerging types
of educational activities w ill help surgeons continue to pro-
vide high-quality care as cognitive requirements, skills, and
■ CONCLUSION AND RECOMMENDATIONS: A
standards of care evolve throughout their careers.
BALANCED PORTFOLIO OF CME
To keep abreast of new know led ge, to acqu ire new skills,
and to avoid becom ing obsolete, every su rgeon shou ld
■ REFERENCES
have a p lan for lifelong learning and p rofessional d evelop - 1. ACCME’s Glossary of Terms and Abbreviations. Chicago, IL: Accred itation
Cou ncil on Continuing Med ical Ed u cation; revised Ap ril 2010. Avail-
ment u sing princip les of effective ad u lt ed u cation and able at: http:// ww w.accme.org/ index.cfm / fa/ hom e.library/ home.cfm .
behavior change. This w ill requ ire an investm ent of tim e Accessed October 23, 2010.
and effort and involve a m ixture of active and p assive 2. The Am erican College of Su rgeons. Cod e of Professional Cond u ct. J
Am Coll Surg 2003;197(4):603–604.
learning exp eriences. As w ith any investm ent, an organ- 3. Rosof AB, Felch WC, ed s. Continuing Medical Education: A Primer, 2nd
ized plan and a balanced portfolio of CME and profes- ed . Westp ort, CT: Praeger; 1992.
sional d evelop m ent activities w ill p ay m ore d ivid end s 4. State Medical Licensure Requirements and Statistics, 2011. Chicago, IL:
Am erican Med ical Association, 2010. Available at: w w w.am a-assn.org/
than a rand om one. am a1/ pu b/ up load / m m / 40/ continu ing-m ed ical-ed u cation-licensu re.
An organized plan should inclu d e a balance across pd f. Accessed October 23, 2010.
typ es of learning activities that inclu d e 5. Mann DV, Gelu la MH . H ow to facilitate self-d irected learning. In:
Davis D, Barnes BE, Fox R, ed s. The Continuing Professional Development
■ general inform ation aw areness Of Physicians: From Research to Practice. Chicago, IL: Am erican Med ical
Association Press; 2003, p p . 121–143.
■ answ ering qu estions 6. Pathm an DE, Konrad TR, Freed GL, et al. The aw areness-to-ad herence
■ skill training m od el of the steps to clinical guid eline com pliance: the case of ped i-
■ p erform ance review. atric vaccine recom m end ations. Med Care 1996;34(9):873–889.
7. 2006 Updated Decision-Making Criteria Relevant to the Essential Areas and
Scanning for new inform ation includ es read ing a selec- Elements. Chicago, IL: Accred itation Cou ncil for continu ing Med ical
Ed ucation. Available at: http:// w ww.accme.org/ d ir_d ocs/ d oc_upload /
tion of m ed ical and su rgical jou rnals regu larly. In a teach- f4ee5075-9574-4231-8876-5e21723c0c82_upload d ocum ent.pd f. Accessed
ing environm ent, a “jou rnal club” stim u lates regu lar October 23, 2010.
read ing. It is imp ortant to have a group of professional su r- 8. MOC Competencies and Criteria. Chicago, IL: American Board of Medical
Specialties. 2010 http:// www.abms.org/ Maintenance_of_Certification/
gical colleagues w ith w hom to interact on a regular basis to MOC_com petencies.asp x. Accessed October 23, 2010.
exchange id eas and inform ation. Local and regional su rgi- 9. ABMS Maintenance of Certification. American Board of Med ical Specialties.
cal societies and specialty societies serve this purp ose. One 2010 Available at: http:// www.abms.org/ Maintenance_of_Certification/
ABMS_MOC.aspx. Accessed October 23, 2010.
shou ld take ad vantage of CME offerings sp onsored by p ro- 10. Maintenance of Certification (MOC) – Overview. Chicago, IL: Am erican
fessional societies and acad em ic centers, w hich are m ore Board of Surgery, 2010. Available at: http :// hom e.absu rgery.org/
likely than ind ustry-controlled events to be free of bias. d efault.jsp ?exam -m oc. Accessed October 23, 2010.
11. Bu yske J. For the p rotection of the p u blic and the good of the sp ecialty:
From this kind of scanning activity, one shou ld regu larly m aintenance of certification. Arch Surg 2009; 144:101–103.
choose som e top ics for in-d ep th stu d y on the basis of self- 12. SESAP 14: Surgical education and self-assessment program. Chicago, IL.
evalu ation and on goals that are both personal and institu - Division of Ed u cation, Am erican College of Su rgeons; 2010. Available
at: http:// www.facs.org/ fellows_info/ sesap/ sesap.html. Accessed Octo-
tional. One shou ld choose focused courses that fill a gap in ber 23, 2010.
know led ge, give need ed inform ation, engage particip ants 13. Bu rley C. What su rgeons shou ld know abou t 2008 PQRI rep orting
in active learning experiences, and im part inform ation and options. Bull Am Coll Surg 2008;93(7):8–9.
14. H u ghes T, Tanzm an H , Shabot M. The ACS Case log system : 2009
skills that have im m ed iate p ractical ap p lication. up d ate. Bull Am Coll Surg 2009:94(9):10–17.
Whenever possible, one should try to introduce new 15. ACCME Annual Report Data 2009. Chicago, IL: Accred itation Cou ncil
technologic applications in conjunction w ith colleagues and for Continuing Med ical Ed ucation, 2010. Available at: w w w.accm e.org/
d ir_d ocs/ d oc_u pload / f2e89864-b4c1-428f-8ebe-1ba197a31928_u p load
have a plan to evaluate the outcomes of the changes that d ocum ent.p d f. Accessed October 23, 2010.
have been mad e. This is alw ays the most d ifficult yet the 16. Am erican College of Su rgeons. Stand ard s for ad vanced cou rses in new
most critically important component of the improvement technologies. Bull Am Coll Surg 1998;83:36.
17. Com m ittee on Ethics, Am erican College of Su rgeons. Gu id elines for
cycle. Errors and complications persist in clinical practice collaboration of ind u stry and su rgical organizations in sup port of
w hen surgeons are unw illing to record and confront their research and continu ing ed u cation. Bull Am Coll Surg 2001;86:30–31.
CHAPTER
Surgical Credentials
Mary E. Klingensmith
■ INTRODUCTION 6. organ transp lantation

7. p ed iatric su rgery
The processes lead ing to board certification and hosp ital 8. su rgical critical care
cred entialing are often confu sing to su rgical trainees or 9. su rgical oncology
those new to the Am erican health care system . This chap ter 10. trau m a/ bu rns and acu te care su rgery
w ill seek to ou tline these tw o areas, p ointing out w here 11. vascu lar su rgery.
they overlap and how they relate to the requ irem ents for
resid ency training in su rgery. Evolving issues in cred ential- The ABS goes on to state that the exp ected know led ge
ing and the certification p rocess w ill also be d iscu ssed w ith and p erform ance of a certified su rgeon inclu d es
regard to the m aintenance of certification initiative.
1. a com p rehen sive clinical know led ge w ithin th e con -
tent areas, inclu d ing ep id em iology, anatom y, p hysi-
■ BOARD CERTIFICATION ology, clinical p resentation, an d p ath ology (in clu d in g
The Am erican Board of Su rgery (ABS) is a mem ber of the neop lasia);
Am erican Board of Med ical Specialties (ABMS). The ABMS 2. know led ge of the scientific found ations of w ou nd heal-
is the u m brella organization for 24 m ed ical sp ecialty ing, infection, flu id management, shock/ resu scitation,
board s. In early 2009, m ore than 85% of all licensed p hysi- im m u nology, antibiotic u sage, m etabolism , and nu tri-
cians in the United States w ere certified by at least one tion;
ABMS m em ber board (1). Thu s, board certification statu s is 3. experience in clinical evaluation including the appropri-
clearly recognized as a critical com p onent of the p rofes- ate use of imaging, indications for surgery and nonsurgi-
sional d ossier of all p hysicians in the United States, su r- cal treatment, preoperative, operative and postoperative
geons inclu d ed . care, and management of comorbidities and complica-
The ABS w as fou nd ed in 1937 as a p rivate, volu ntary, tions;
nonp rofit organization w ith three p rim ary p u rp oses: 4. extensive experience in m inim ally invasive surgery for
d iagnosis and treatm ent in the essential content areas,
1. To cond u ct exam inations of accep table cand id ates w ho inclu d ing basic and ad vanced laparoscopic proce-
seek certification or m aintenance of certification by the d u res;
board ; 5. su bstantial exp erience in d iagnostic and therap eu tic
2. To issu e certificates to all cand id ates m eeting the board ’s end oscop y, inclu d ing colonoscop y, esop hagogastro-
requirem ents and satisfactorily com pleting its pre- d u od enoscop y, and bronchoscop y;
scribed exam inations; 6. resu scitation of critically ill p atients, inclu d ing trau m a
3. To im p rove and broad en the op p ortu nities for grad u ate victim s;
ed u cation and training of surgeons (2). 7. airw ay intu bation;
Accord ing to ABS d efinitions, “general su rgery” is a 8. consciou s sed ation;
d iscipline that encom passes the follow ing content areas (2): 9. d iagnostic u ltrasonograp hy;
10. noninvasive d iagnostic evaluation of the vascular sys-
1. alim entary tract tem ;
2. abd om en and its contents 11. sentinel lym p h nod e m ap p ing for breast cancer and
3. breast, skin, and soft tissue melanom a;
4. end ocrine system 12. team -based interd iscip linary care of
5. head and neck su rgery a. term inally ill p atients, to inclu d e p alliative care and
the m anagem ent of p ain
b. m orbid obesity, to inclu d e m etabolic d erangem ents
Mary E. Klingensmith: Washington University School of and w eight-loss su rgery
Med icine, Saint Lou is, MO 63110. c. geriatric su rgical patients.
28
Chapter 5 • Surgical Credentials 29
It is also noted by the ABS that the certified su rgeon is ■ The examination process
expected to be familiar w ith com m on d iseases and opera-
tions in thoracic su rgery, plastic and reconstructive su rgery, After the ABS has accepted the initial application, the appli-
and u rgent/ em ergent problem s in gynecologic, neu ro- cant is eligible for the examination process. This has tw o
logic, orthop ed ic, and urologic su rgery (2). parts. A w ritten examination (called the Qualifying Examina-
To be ad m itted to the board certification process, the res- tion) is to be taken in August of the year follow ing completion
id ency program d irector must end orse a cand id ate’s appli- of training. If the cand id ate passes this exam, an oral exam
cation, ad d ing a statement that attests to an applicant’s (the Certifying Examination) follows. This exam is held in sev-
ap propriate ed ucational experience in the above areas and eral cities around the United States, with examinees directed
that signifies the app licant has the ju d gm ent, know led ge, to the nearest test site. If the examinee passes the oral exam, a
and skills to be consid ered for board certified statu s. certificate signifying board certification in surgery and desig-
nating the examinee as a diplomat of the ABS is issued.
(For updated information and any revisions in Board exami-
■ STEPS LEADING TO BOARD CERTIFICATION nation admissibility requirements, see www.absurgery.org. The
Web site is updated annually.) Readers are encouraged to access
■ Prerequisites this information frequently during surgical training to stay
Cand id ates for board certification m u st have com pleted abreast of any changes in Board examination admissibility
training in an accred ited general su rgery resid ency p ro- requirements that might occur.
gram . Accred ited p rogram s m u st m eet stand ard s set forth
by the Accred itation Cou ncil for Grad u ate Med ical Ed u ca-
tion (ACGME). Within the ACGME, each specialty has its
■ MAINTENANCE OF CERTIFICATION
ow n Resid ency Review Com m ittee (RRC). Ind ivid u al The certificate issued by the board is valid for up to 10 years.
RRCs collaborate w ith the specialty board (i.e., ABS) to In ord er to m aintain certification, a recertification exam is
d eterm ine the com ponents that shall be d eem ed essential requ ired , in ad d ition to ad d itional com p onents that com -
for a p rogram to be accred ited . Accred ited p rogram s p ro- p rise “Maintenance of Certification” (MOC). This recertifi-
d u ce grad u ates that are potentially board eligible. cation exam can be taken as early as 7 years follow ing
As part of a process overseen by both the ABS and RRC, certificate issu ance bu t no later than 10. This exam ination is
a m inim u m nu m ber of cases in each of the essential content only one com p onent of the MOC p rocess.
areas listed above is d eterm ined for board exam ination The ABMS has led an effort term ed the Maintenance of
ad m issibility. Resid ents mu st keep track of the op erations Certification © (MOC) p rogram , an initiative that has
they p erform d u ring training, as they count tow ard these been several years in the m aking. The p rocess has evolved
minim u m nu m bers. Upon com p letion of training, these as the m em ber board s of the ABMS have collectively
case logs m u st be su bm itted to the ABS as part of the initial agreed that the “snap shot” evalu ation of p hysicians that
app lication for board exam ination. This app lication also is available throu gh the cu rrent system of certification
includ es areas in w hich the trainee m ust list the rotation and recertification d oes not cap tu re a p hysician’s tru e
sched u les for the 5 years of general surgery training to com p etency and efforts at p ractice assessm ent and
d em onstrate that the trainee has acqu ired ad equate experi- im p rovem ent (1). The ABS has rep orted that cu rrent
ence in each of the essential content areas. Ad d itionally, the recertification exam statistics ind icate that recertification
board sp ecifies m inim um nu m bers of w eeks and m onths exam inees w ho are rou ghly 30 years ou t of training fail
that m u st be com p leted in variou s acad em ic years and the recertification exam at m u ch higher rates than d o
variou s content and lead ership areas; these too m u st be those closer to their training (3). MOC w ill allow ad d i-
specified in the application for exam ination (2). Fu rther, tional asp ects of a p ractitioner ’s qu alifications to be con-
beginning w ith applicants w ho com plete training in sid ered as p roof of com p etency.
2009–2010 (and thereafter), all app licants w ill be requ ired MOC has fou r p rim ary com p onents (1):
to have su ccessfu lly com p leted Ad vanced Card iovascu lar
1. Evid ence of p rofessional stand ing
Life Su p p ort (ACLS), Ad vanced Trau m a Life Su p p ort
2. Evid ence of a com m itm ent to lifelong learning and
(ATLS), and Fu nd am entals of Lap aroscopic Surgery (FLS)
involvem ent in period ic self-assessm ent processes
at any tim e d u ring training (2).
3. Evid ence of cognitive exp ertise (cu rrently the w ritten
Other requ irem ents for certification in su rgery inclu d e
recertification exam ination)
“satisfactory ethical, professional, and m oral stand ing,”
4. Evid ence of evalu ation of p erform ance in p ractice.
active p ractice in surgery w ith ad m itting privileges in an
accred ited health care organization (or cu rrently in p u rsu it These com p onents are based on the six com p etency
of ad d itional grad u ate ed u cation in su rgery or a su rgical areas d efined by the ACGME for resid ency training (m ed -
subsp ecialty), and permanent licensure to p ractice m ed i- ical know led ge, p atient care, interp ersonal and com m uni-
cine in a state or jurisd iction of the United States or cation skills, p rofessionalism , p ractice-based learning and
Canad a. All of these prerequisite com ponents are rep reim p rovem ent, and system s-based p ractice). Eventu ally,
sented on the initial ap p lication for board certification. evalu ation based on the six com p etency areas w ill be a
seam less p rocess that begins in resid ency training and con- ■ CANADIAN AND INTERNATIONAL TRAINEES
tinu es throu ghou t a su rgeon’s career.
The p ortion of MOC involving evalu ation of p erform - Ap plicants w ho have trained in Canad a in u niversity resi-
ance in p ractice (“ou tcom es”) is critical to the ABS MOC d ency p rogram s in su rgery, w hich are accred ited by the
process. Particip ation in a national, regional, or local su rgi- Royal College of Physicians and Su rgeons, are d eem ed eli-
cal ou tcom es d atabase is a requirement of MOC (3). It is gible for board exam ad m issibility. The other board
anticip ated that MOC w ill evolve over tim e; read ers are requ irem ents (noted above in the “Prerequ isites” section)
encouraged to stay abreast of the ABS requ irem ents in this m u st also be m et.
area. Dip lom ates of the ABS w ho certify or recertify after Applicants from abroad are not granted cred it for their
Ju ly 1, 2005, m u st com ply w ith the ABS MOC program to training or p ractice exp eriences d irectly, no m atter how
maintain their certification (2). accom p lished . On a case-by-case basis, the ABS w ill con-
sid er granting partial cred it for training abroad only upon
the request of a p rogram d irector of an accred ited resi-
■ FAILURE TO PASS BOARD EXAMINATIONS d ency p rogram in the United States. This p rogram d irector
m u st have observed the ap p licant as a ju nior resid ent for 9
■ Qualifying examination to 12 m onths and d esire to ad vance the ap p licant to a
Applicants have five op portunities to take the qualifying higher level in that p rogram . This cred it is not transferable
exam ination (QE) w ithin a 5-year period follow ing to another program and is not granted until the ap plicant
approval of the initial ap plication. Applicants w ho are successfully com p letes the accred ited resid ency-training
unable to p ass the exam after these five attem pts or w ho p rogram . Ap p licants from Canad ian p rogram s m u st have
fail to p ass the exam ination w ithin 5 years of com p leting com p leted all of their training in Canad a and w ill not be
resid ency training are allow ed eligibility only if they com - ad m itted to the board certification p rocess if som e of that
plete a d efined “read m issibility pathw ay.” training w as in countries ou tsid e of the United States or
The ABS has expanded and refined the readmissibility Canad a. Thu s, all international ap p licants m u st spend at
process to include tw o options. In the first “standard path- least som e p ortion of their p rofessional training in a U.S.
way,” candidates must complete an additional 12 months of resid ency program in ord er to be board eligible.
structured education in an ACGME-approved residency
program, w hich is essentially an add itional year of training
designed by the resid ency program and approved in
■ SUBSPECIALTY CERTIFICATION
ad vance by the ABS. The second, “alternate pathway” The ABS also sponsors specialty certifications in the areas of
recently created and mod ified by the ABS involves a tw o- vascular su rgery, p ed iatric su rgery, surgery of the hand ,
step process. First, candidates must submit evidence of con- hospice and palliative med icine, and surgical critical care.
tinuing med ical education (CME) activity, completion of the The Am erican Board of Colon and Rectal Su rgery (w w w.
most recent version of the American College of Surgeons abcrs.org) and the American Board of Thoracic Surgery
Surgical Ed ucation and Self-Assessment Program (SESAP), (w w w.abts.org) sponsor subspecialty certification in their
reference letters, and an operative experience report. Upon respective areas. The certifying exam inations in these sub-
approval of this initial application, the applicant must take specialties are taken after fellow ship training. Currently,
and pass two examinations, one d erived from the In-Train- there is no separate certification board for transplant su r-
ing Examination and the other from the latest tw o versions of gery, hep atobiliary su rgery, gastrointestinal su rgery, breast
SESAP. Upon completion of either of these pathways, the surgery, oncologic su rgery, or m inim ally invasive su rgery,
applicant w ill be ad missible to the QE for five opportunities althou gh fellow ship programs in these areas offer certifi-
within five years. If the applicant is again unsuccessful in cates at the completion of such ad d itional training. These
passing the QE, s/ he must reenter formal residency training certificates signify that the bearer has completed training in
for PGY-4 and PGY-5 training in an accredited training pro- the subspecialty area. Su pervision of these p rogram s is
gram to regain admissibility for a third five-year period. d one by ind ivid u al societies w hose m em bership d eter-
mines the program requirements; the d egree of supervision
can vary w id ely among the specialties.
■ Certifying examination
Cand id ates have five opportunities to take the certifying
exam ination in the 5 years follow ing su ccessfu l com p letion
■ HOSPITAL PRIVILEGING
of the QE. If the applicant is unsuccessful in passing the cer- The p rovision of the rights to ind ivid u al su rgeons to ad m it
tifying examination w ithin these time lim its, read m issibility and treat p atients is d etermined on a local level by ind ivid -
may be sought in either of the pathw ays d escribed above. u al hosp itals or health care organizations. To be eligible
(For more information, see www.absurgery.org. The Web site for the cred entialing p rocess, ap p licants m u st show either
is updated annually.) Readers are encouraged to access this infor- board certification (or eligibility)—w hich is requ ired by
mation frequently to stay abreast of changes that might occur in the vast m ajority of hosp itals—or evid ence of resid ency
the readmission criteria. training or p ractice exp erience in the area for w hich the
Chapter 5 • Surgical Credentials 31
app licant d esires privileges. It is u nusual for acad em ic inclu d es d ocum entation of training and experience in the
med ical centers to grant clinical privileges to su rgeons w ho relevant areas, inclu d ing case lists and a su m m ary letter
are not board certified . Conversely, som e hospitals in areas from the resid ency p rogram d irector attesting to the accu -
of the United States w ith large p op u lations of u nd erserved racy of the list and to the ap p licant’s ability. Other inform a-
patients d o occasionally grant p rivileges w ithou t the tion, su ch as ed u cation, licensu re inform ation, and p roof of
requ irem ent for board certification if all other requ irem ents board certification, are also requ ired .
are m et. The ap p licant m u st also m ake sp ecific requ ests for
Before the cred entialing process can begin, ap p licants p rivileges in a given area. For instance, p erm ission to per-
mu st p ossess an u nrestricted state m ed ical license, fed eral form vascu lar p roced u res or m inim ally invasive abd om i-
and state Dru g Enforcem ent Ad m inistration (DEA) nu m - nal proced u res m u st be specifically requested and granted
bers, and variou s id entifying num bers need ed for charge before the ap p licant m ay p erform su ch op erations. Obvi-
reim bu rsem ent: Med icare/ Med icaid p rovid er nu m bers, ou sly, the ap p licant shou ld be able to d em onstrate ad e-
UPIN s (u niqu e p rovid er id entification nu m bers), and qu ate training in the areas of p ractice requ ested . Often,
fed eral and state tax id entification n u m bers. Th e h osp ital su ch requ ests are facilitated by an ap p lication checklist for-
cred entialing com m ittee can usu ally su pply the list of m at, in w hich p roced u res of variou s typ es are grou ped
requ irem ents and provid e applications to secu re these var- together to facilitate a su rgeon’s requ est for p rivileges, for
iou s item s. Most hospitals also require applicants to sim u l- exam p le, in vascu lar su rgery, that w ou ld encom pass a typ-
taneou sly com p lete p ap erw ork for the variou s insu rance ical practice in that area.
com panies and health m aintenance organizations (H MOs) If an ap p licant d oes not have exp erience in an area for
in their area to insu re reim bu rsem ent for services once w hich p rivileges are requ ested , op tions are available to
practice begins. p rovid e p relim inary or p rovisionary p rivileges. Su ch a
situ ation m ight arise for p roced u res d evelop ed after an
ind ivid u al has com p leted form al resid ency training (as
■ HOSPITAL CREDENTIALS COMMITTEES occu rred w ith a large nu m ber of p racticing su rgeons w ith
the ad vent of lap aroscop ic cholecystectom y in the late
H ospitals d eterm ine the criteria for cred entialing in the
1980s and early 1990s). In the absence of form al resid ency
variou s p ractice areas. Typically, several su rgeons from d if-
training in the p roced u re, d ocu m entation of attend ance of
ferent d isciplines serve on a su rgical cred entialing com m it-
a d id actic cou rse d ed icated to the p roced u re that inclu d es
tee, w hich is chaired by the hosp ital’s chief of su rgery. This
hand s-on instru ction (in anim al or cad aver lab or live
ind ivid u al is u ltim ately resp onsible for d eterm ining that
op erating room ) p lu s p lanned p roctor/ m entor exp erience
an ap p licant has m et the criteria set by the com m ittee and
m ight be su fficient for p relim inary p rivileging. Som e cre-
possesses the know led ge, ju d gm ent, and skills necessary to
d entialing bod ies accep t p ractical exp erience as a first
perform the requ ested clinical activities.
assistant in su ch p roced u res, w ith d ocu m entation from a
The Joint Cou ncil on Accred itation of H ealthcare Orga-
m entor or p recep tor requ ired . It is im p ortant to be aw are
nizations (JCAH O) ou tlines the process for cred entialing
of the requ irem ents of ind ivid u al cred entialing com m it-
and d elineation of clinical privileges this w ay: “The cred en-
tees to ensu re the best chance that p rivileges w ill be
tialing p rocess inclu d es a series of activities d esigned to
granted .
collect relevant d ata that w ill serve as the basis for d eci-
Althou gh it is not alw ays a requirem ent of an ind ivid -
sions regard ing . . . d elineation of clinical privileges for
u al hosp ital, the su rgeon requ esting p rivileges in a given
ind ivid u al m em bers of the m ed ical staff . . . the requ ired
area shou ld carefu lly consid er institu tional support for
inform ation should inclu d e d ata on qualifications such as
p rogram m atic p roced u res. This su p p ort has proven to be
licensu re and training experience [and ] d ata on actu al per-
esp ecially im p ortant in the area of bariatric su rgery, in
form ance that [are] collected and assessed initially and in
w hich m u ltid iscip linary care of the p atient has been associ-
an ongoing p rocess” (4).
ated w ith im p roved p atient ou tcom e (5).
Uniform stand ard s exist for privileges in various areas.
These are often sponsored by specialty societies. For
instance, in the field of m inim ally invasive su rgery, the ■ RECREDENTIALING
Society of Am erican Gastrointestinal End oscop ic Su rgeons
Som e hospitals w ill grant prelim inary privileges to sur-
(SAGES) has a cred entials com m ittee that u pd ates and
geons d u ring the first year, w ith a requ est for reapplication
expand s the suggested criteria for privileges in variou s
after one year. Increasingly, at the tim e of reapplication,
areas of m inim ally invasive surgery as a resou rce for hosp i-
surgeons are being asked to provid e information regard ing
tal cred entialing com m ittees (w w w.sages.org).
the ou tcom e of their w ork as evid ence to su pport the grant-
ing of fu ll p rivileges.
The recred entialing p rocess is thereafter an annu al or a
■ APPLYING FOR PRIVILEGES
biannu al event. Most hosp itals also requ ire CME cred its in
Ind ivid u als ap p lying for p rivileges m u st su bm it inform a- the area of practice and expertise to d em onstrate continued
tion requ ested by the hospital comm ittee. Typically, this efforts at p ractice im p rovem ent.
■ DENIAL OF PRIVILEGES ■ REFERENCES

Ind ivid u als ap p lying for p rivileges in a given area shou ld 1. ABMS Web site. Available at: w w w.abm s.org. Accessed Febru ary 16,
2009.
be certain they p ossess the qualifications for w ork in that 2. Booklet of information, 2008–2009. The Am erican Board of Su rgery; 2009.
area. If p rivileges are d enied , the ap peals process ou tlined Available at: w w w.absu rgery.org. Accessed Febru ary 16, 2009.
by the hosp ital cred entials com m ittee should be follow ed . 3. Bu yske J. For the p rotection of the p u blic and the good of the sp ecialty.
Arch Surg 2009;144(2):101–103.
H ow ever, ap p licants should be aw are that if a form al 4. Joint Com m ission on Accred itation of H ealth Care Organizations
d enial of p rivileges is returned , such inform ation is (JCAH O). The cred entialing p rocess. CAMH: Comprehensive accreditation
rep orted to the N ational Practitioner Databank and kep t as manual for hospitals. Oakbrook Terrace, IL: JCAH O; 2000:MS5–MS7.
5. Am erican College of Su rgeons. Recom m end ations for facilities p erform -
part of that p ractitioner ’s perm anent file. ing bariatric su rgery. Bull Am Coll Surg 2000;85(9):20–23.
CHAPTER
6
Understanding Variation in
Surgical Outcomes
J ustin B. Dimick and J ohn D. Birkmeyer
There is grow ing recognition that the risk of d eath after Chance can cau se tw o typ es of errors in qu ality m eas-
su rgery is d eterm ined in large p art by the p lace of su rgery u rem ent. First, extrem e ou tcom es m ay be attribu ted to
and the p erson w ho perform s the proced u re. qu ality w hen they are really d u e to chance alone (Typ e I
Seminal stu d ies in card iac surgery, cond u cted m ore errors). With m any qu ality m easu rem ent p latform s, for
than tw o d ecad es ago, d ocu mented w id e variation in m or- exam p le, hosp itals are labeled as “ou tliers” if their ou t-
tality rates across both hospitals and su rgeons (1,2). More com es are statistically d ifferent from exp ected (e.g., w hen
recent stu d ies have su ggested sim ilar variations in p er- the 95% confid ence intervals arou nd their outcom e rates
form ance w ith general and vascular surgery (3,4). A grow - fail to overlap the p op u lation average). Depend ing on
ing bod y of evid ence also d ocu m ents that ou tcom es vary w here the statistical threshold for ou tliers is set, som e hos-
accord ing to a nu m ber of provid er attributes, esp ecially p itals w ill be labeled ou tliers based on chance alone.
provid er volu m e and subspecialty training (5,6). These Concep tu al Typ e I errors are often m ad e w hen evalu at-
stu d ies on “variations” in ou tcom es su ggest su bstantial ing a hosp ital or su rgeon w ith no d eaths (“zero m ortality”)
op p ortu nities for imp roving the ou tcom es of su rgical care. in a p articu lar p roced u re. While having no d eaths is con-
sid ered a sign of qu ality, it is also p ossible that su ch
p rovid ers have no d eaths sim p ly d u e to chance (i.e., good
■ UNDERSTANDING VARIATION IN OUTCOMES
lu ck), esp ecially if they p erform a low nu m ber of surgeries.
Su rgeons often m ake the m istake of attribu ting variations A recent stu d y u sing national Med icare d ata on five su rgi-
in su rgical ou tcom es as variations in qu ality. Trad itional cal p roced u res, d em onstrated that zero m ortality hospitals
morbid ity and m ortality conferences often encou rage this (no d eaths d u ring 3 years) had the sam e or higher m ortal-
view by exp ecting su rgeons to accep t blam e for all ad verse ity d u ring the follow ing year (8). This so-called “Zero Mor-
outcom es. H ow ever, in reality surgical outcom es m ay vary tality Parad ox” w as m ost striking for p ancreatic resection,
for other reasons. In a m ore com p lete conceptu al m od el, w here a history of no d eaths over a 3-year p eriod w as asso-
the so-called “Calcu lu s of qu ality,” variation in su rgical ciated w ith a 30% increased risk of d eath in the su bsequent
ou tcom es can be attribu ted to three contribu ting factors: year. This p arad oxical find ing—that hosp itals w ith no
chance, case m ix (i.e., patient factors), and quality of care d eaths are actu ally low er qu ality—is likely d u e to the w ell-
(7). Althou gh the m ain them es in this review ap p ly to all know n relationship betw een low volu m e and high m ortal-
outcom es, w e focus p rim arily on surgical m ortality, reflect- ity for p ancreatic resection. In other w ord s, for this
ing the pred om inance of this m easu re in existing literature op eration, hosp itals w ith no d eaths are m ore likely to be
and ongoing p olicy initiatives. “lu cky” than “good ” (8).
Typ e II errors occu r w hen chance obscu res real d iffer-
ences in qu ality. One recent stu d y exam ined seven surgical
■ CHANCE
p roced u res for w hich hosp ital m ortality rates had been
Su rgical ou tcom es can vary across p rovid ers sim p ly d u e to recom m end ed as qu ality ind icators by the Agency for
chance (i.e., good or bad lu ck). H ospital-specific ou tcom e H ealth care Qu ality & Research (AH QR) (9). For only one
measu res are often based on sm all num bers of ad verse op eration, coronary artery byp ass grafting (CABG), d id the
events and su rgical cases, resu lting in statistically im p re- majority of U.S. hospitals perform enough cases over a 3-year
cise or “noisy” estim ates of perform ance. Chance is p artic- p eriod to d etect w ith statistical confid ence m ortality rates
ularly im p ortant w hen the event rate is low (e.g., m ortality at least tw ice the national average (Fig. 6.1). For m ost pro-
rate after cholecystectom y) or the p roced u re is u ncom m on ced u res, few hosp itals had su fficient caseload s to meet this
(e.g., p ancreatectom y). low bar of statistical pow er.
There is grow ing interest in the u se of statistical tech-
niqu es for better d ealing w ith chance. Reliability ad just-
Justin B. Dimick, John D. Birkmeyer: University of m ent, an ap p lication of hierarchical m od eling, red u ces
Michigan, Ann Arbor, MI 48109. statistical “noise” in p rovid er-sp ecific ou tcom e m easu res
33
FIGURE 6.1. Big problems with small 100%

samples: The proportion of hospitals in the 90%
United States with sufficient caseloads
(sample size) to reliably use mortality rates
to measure quality. 80%
60%
40%
33%
25%
20%
8%
2% 1% 1%
0%
Coronary Craniotomy Pediatric heart Repair of Pancreatic Esophageal Hip
bypass surgery surgery abdominal resection resection replacement
aneurysm
(10). This techniqu e “shrinks” the point estim ate (e.g., of the im pact of this ad ju stm ent on hospital qu intiles. Sorting
op erative m ortality) for each hosp ital back tow ard the hosp itals sim ply on observed m ortality show s that m ortal-
overall p op u lation rate. The d egree of shrinkage d ep end s ity rates varied from 1.4% to 11.0% across hosp ital quintiles.
on sam p le sizes and the relative p recision of the p oint esti- H ow ever, on ranking hospitals on their reliability-ad ju sted
mate. Su ch techniqu es have only recently been app lied in mortality, the mortality rates varied consid erably less, from
health care. In a land m ark paper, H ofer et al. d em onstrated 3.3% to 6.3%. Although the almost tw o-fold variation in
the valu e of ad ju sting for reliability in p rofiling p hysician m ortality still su ggests am p le op p ortu n ity for qu ality
qu ality in am bu latory care (11). im p rovem ent, these d ata u nd erscore the im p ortance of
We u sed sim ilar hierarchical mod eling techniques to accou nting for chance in und erstand ing variation in hospi-
assess the role of chance in explaining apparent hosp ital tal outcomes.
variation in su rgical m ortality rates. With CABG, for exam -
ple, m ore than half of the observed variation cou ld be
attribu ted to statistical noise. Figure 6.2 show s hosp ital
■ CASE MIX
mortality rates before and after using hierarchical m od el- Differences in p atient factors (e.g., case m ix) also contribute
ing to “ad ju st for reliability.” After ad justm ent for reliabil- to variation in ou tcom es. Som e p rovid ers m ay have w orse
ity, there is a d ram atic red u ction in the variation across ou tcom es becau se they treat sicker, higher risk patients
hosp itals, im p lying that a large p rop ortion of observed than other hosp itals. Althou gh risk ad ju stm ent in com par-
d ifferences are d u e statistical “noise.” Figu re 6.3 show s isons of p rovid er p erform ance is obviou sly im p ortant, the
FIGURE 6.2. Risk-adjusted mortality rates for coro- 20

nary artery bypass surgery at 20 hospitals before and Coronary artery bypass
after adjusting for statistical reliability. 18
Risk-adjusted mortality rates (%)
16
14
12
10
8
6
4
2
0
Before After
adjusting for adjusting for
reliability reliability
Chapter 6 • Understanding Variation in Surgical Outcomes 35
Coronary artery bypass FIGURE 6.3. Variation in risk-adjusted mortal-

12.0 ity across hospital quintiles for coronary artery
bypass surgery before and after adjusting for
reliability.
Risk-adjusted mortality (%) (2003-04)
10.0 9.6%
8.0
6.0%
6.0 5.6%
4.9%
4.2% 4.4%
3.9%
4.0
3.1% 3.2%
2.0
1.2%
0.0
1 2 3 4 5 1 2 3 4 5
Not adjusted for reliability Adjusted for reliability
Quintiles of Hospital Mortality

(2003-04)
evid ence that d ifferences in p atient factors explain varia- colon resection w ere highly correlated (Fig. 6.4). These d ata
tions in su rgical ou tcom es is m ixed . are not m eant to im p ly that p atient factors are not im por-
The im p ortance of risk ad ju stm ent is a fu nction of the tant d eterm inants of su rgical risk. Rather, they suggest that
pop u lation being stud ied . In intensive care, for exam p le, su ch factors contribu te little to exp laining variation in p ro-
the p hysiologic status of the p atient (e.g., APACH E score) ced u re-sp ecific ou tcom es across hosp itals and su rgeons.
is an im portant d river of ou tcom es and m ay vary exten- These find ings also have im p ortant im p lications for
sively across hosp itals. In contrast, w ith elective su rgery, qu ality m easu rem ent p latform s, su ch as ACS-N SQIP. As
patients tend to be very hom ogeneou s w ith resp ect to p resently d esigned , the risk-ad ju stm ent m od els for ACS-
physiologic statu s (e.g., they all w alk throu gh the d oor). N SQIP, and other ou tcom es-based registries, requ ire the
H ow ever, typ es of proced ures perform ed at d ifferent hos- expensive collection of detailed d ata from medical records.
pitals m ay vary extensively. Large teaching hosp itals p er- Given that case mix contributes little to variations in hospital
form m ore com plex, higher risk proced u res than sm all ou tcom es for sp ecific p roced u res, w e shou ld p ursu e m ore
com m u nity hosp itals. Even w ithin otherw ise com p arable
hosp itals, p roced ure m ix varies accord ing to the sp ecific
practices of the su rgeons op erating there. For this reason,
Correlation = 0.92
ad ju sting for p roced ure m ix is crucial for fair com p arisons
of hosp itals’ overall su rgical m orbid ity and m ortality rates, 70
for exam p le, as p rovid ed by th e Am erican College of
Su rgeons- N ational Su rgical Qu ality Im p rovem ent Pro- 60
gram (ACS-N SQIP).
Adjusted morbidity rate (%)
In con trast, th e im p ortan ce of risk ad ju stm en t m ay 50

be overstated for interpreting proced u re-specific com par-
isons, largely becau se case m ix usu ally varies little across 40
hospitals am ong patients und ergoing the same op eration.
For exam p le, w e examined publicly reported m ortality 30
rates for 35 hosp itals perform ing CABG in N ew York State
in 2000–2001, as d erived from their state-m and ated clinical 20
registries (12). Observed m ortality rates varied consid er-
ably, from less than 1% to over 4%. H ow ever, risk ad ju st- 10
ment had negligible im pact in red ucing app arent variation
in ou tcom es—u nad justed and ad ju sted hospital m ortality 0
rates w ere nearly id entical (correlation 0.95). We cond u cted 0 10 20 30 40 50 60 70
sim ilar analyses of noncard iac p roced u res based on m ore Unadjusted morbidity rate (%)
recent ACS-N SQIP d ata, reaching sim ilar conclu sions. For FIGURE 6.4. Correlation between risk-adjusted and unadjusted hospital
exam p le, risk-ad ju sted and unad ju sted m orbid ity rates for morbidity rates for colon resection.
efficient ap p roaches to risk ad justm ent. For exam p le, variation in hosp ital m ortality rates exp lained by p roce-
em phasis cou ld be placed on d ata collection of the m ost d u re volu m e also varies by p roced u re. In ou r recent analy-
im portant variables (e.g., 5–10 risk factors) rather than the ses of national Med icare d ata, volu m e accou nted for 69% of
70 to 80 variables p resently collected (13). Fu rther, since nonrand om variation in hosp ital m ortality w ith p ancreate-
chance (i.e., “noise”) seem s to be a m ore im portant d river ctom y, 58% w ith abd om inal aortic aneu rysm repair, and
than patient severity, reliability ad justm ent (as d iscussed in only 7% w ith coronary byp ass su rgery (16).
the p reviou s section) shou ld be given at least as m u ch Many stu d ies have also exp lored associations betw een
em phasis as risk ad justm ent. su rgeon volu m e and ou tcom es. In one large stud y of
Med icare p atients, su rgeon volu m e w as inversely related
to m ortality w ith each of eight d ifferent card iovascu lar p ro-
■ QUALITY OF CARE ced u res and cancer resections (17). Besid es d em onstrating
■ Mechanisms underlying variation in outcomes the imp ortance of su rgeon volu me, this stu d y also pro-
vid ed insight into m echanism s u nd erlying the hosp ital vol-
Variation in surgical ou tcom es not attribu table to chance or u m e-ou tcom e relationship . Sp ecifically, this stu d y show ed
case m ix can be reasonably attribu ted to d ifferences across that su rgeon volu m e exp lains a large p rop ortion of the
provid ers in the qu ality of care. In consid ering m echanism s ap p arent hosp ital volu m e effect for som e op erations, bu t
und erlying variation in provid er outcom es, it is u sefu l to it exp lains alm ost none of the hosp ital volu m e effect for
consid er a concep tu al m od el that d escribes su rgical qu ality others. With carotid end arterectom y, for exam p le, su r-
in term s of stru ctu re, process of care, and ou tcom es (14) geon volu m e exp lained 100% of the ap p arent hospital vol-
(Fig. 6.5). u m e effect. In contrast, w ith lu ng resection, only 24% of the
hospital volu m e effect w as attributable to surgeon volum e.
For p roced u res w here ou tcom es are closely related to
■ STRUCTURE OF CARE
su rgeon volu m e, qu ality d ep end s p rim arily on su rgeon-
Stru ctu ral variables are hospital-level resources (e.g., hos- d ep end ent p rocesses, su ch as good ju d gm ent (i.e., w ho to
pital volu m e, ICU staffing, RN staffing levels) or attribu tes op erate on ) or tech nical p roficien cy. For other p roce-
of ind ivid u al p rovid ers (e.g., su rgeon volu m e, su bsp ecialty d u res, p atient ou tcom es m ay d ep end m ore on hosp ital-
training). Stru ctu ral variables im pact outcom es ind irectly level resou rces, inclu d ing nu rsing care and m anagem ent in
by influ encing p rocess of care. Proced u re volu m e is by the intensive care u nit.
far the m ost visible stru ctu ral variable and h as been
linked to surgical ou tcom es for a broad range of opera-
tions. Althou gh there rem ains relatively little d ebate abou t
■ PROCESS OF CARE
the general im p ortance of proced ure volum e, the strength Processes of care refer to the d etails of clinical care d eliv-
of volu m e-ou tcom e relationship s varies w id ely by p roce- ered to p atients. Im p ortant p rocesses inclu d e those
d u re (15). H osp ital volu m e is m ore im portant for high risk related to p atient selection and evalu ation before su rgery,
bu t relatively u ncom m on proced u res (e.g., esophagectom y the p roced u re itself, and other asp ects of p eri- and p ost-
and p ancreatectom y). Conversely, w ith other p roced u res op erative care. Process of care influ ences the frequ ency of
(includ ing coronary bypass, carotid end arterectom y), d if- initial “sem inal” com p lications (e.g., qu ality of op eration
ferences in operative m ortality rates at low volum e and itself, u se of ap p rop riate p rop hylaxis), “d om ino” com p li-
high volu m e hosp itals are m u ch sm aller. Finally, for som e cations (e.g., tim eliness and effectiveness of m anaging
operations (e.g., colon resection) ou tcomes are the sam e at p ostop erative p roblem s), and u ltim ately p atient d eath
high and low volu m e hosp itals. Sim ilarly, the prop ortion of (Fig. 6.5).
FIGURE 6.5. Conceptual model of varia- Structure: Surgeon expertise & Hospital resources (e.g., care protocols,
tion in surgical quality. skill (e.g., volume, 24/7 intensivists, interventional radiology)
training, experience)
Process: Patient selection & Procedure/ Prevention of Recognition &

evaluation intraoperative care complications management of
complications
Outcomes: No complication Seminal Downstream Death

complication complications
Although a list of processes potentially linked to the otomy. Better ou tcom es for high volu m e su rgeons and vas-
ou tcom es of d ifferent su rgical p roced u res w ou ld be exten- cu lar su rgeons w ere no longer statistically significant after
sive, p ayers and policy m akers are cu rrently focu sing on a accou nting for their m ore consistent ad op tion of these fou r
narrow set of p eriop erative care p ractices in their ongoing p ractices (19).
qu ality m easu rem ent initiatives. These includ e m easu res Su ch d ata d o not im p ly that p rocess of care is u nim -
aimed at red u cing risks of surgical site infection (e.g., p ro- p ortant in u nd erstand ing and im p roving su rgical m ortal-
phylactic antibiotic ad m inistration w ithin 60 m inu tes p rior ity. Rather, they su ggest that m any of the m ost im p ortant
to su rgery), venou s thromboembolism , card iac events, and p rocesses m ay be d ifficu lt to m easu re (e.g., good ju d g-
ventilator-acqu ired pneu m onia. These p rocesses w ere m ent in selecting p atients for su rgery, technical skill in the
selected becau se of high-level evid ence linking them to op erating room ). In ad d ition, they u nd erscore the com -
su rgical ou tcom es and p ercep tions that m any w ere u nd er- p lexity of clin ical care an d th e in n u m erable p rocesses of
u tilized by provid ers. care th at collectively d eterm in e good ou tcom es after
H ow ever, it rem ains u ncertain w hether increasing com - su rgery. For m any p roced u res, focu sing on a lim ited set of
pliance w ith this narrow set of processes w ill substantially ind ivid u al p rocesses w ill not be su fficient for u nd erstand -
red u ce variation in su rgical ou tcom es. Provid ing good su r- ing or red u cing variation in ou tcom es.
gical care involves innu m erable, interrelated processes of
care, m any of w hich are unknow n or im m easu rable. Previ-
ous studies focusing on nonsurgical conditions have d emon-
■ OUTCOMES
strated the lim ited ability of ind ivid u al p rocess m easu res to Patient outcom es are obviou sly the end results of clinical
exp lain variation in the end resu lt. For exam p le, Brad ley care. In the context of ou r concep tu al m od el (Fig. 6.5), the
et al. stu d ied relationships betw een the seven Centers for relevant ou tcom es are the initial “seminal” com plication,
Med icare and Med icaid Services/ Joint Com m ission on the d ow nstream “d om ino” com p lications, and m ortality. A
Accred itation of H ealthcare Organizations (CMS/ JCAH O) better und erstand ing of this pathw ay w ill provid e im por-
core p rocess m easu res and m ortality after acu te m yocard ial tant insights into red ucing variations in surgical outcom es
infarction in a national stud y of 962 hospitals (18). Several across p rovid ers.
of these p rocess m easu res w ere statistically significant p re- It is clinically intu itive that p rovid ers w ith high m ortal-
d ictors of m ortality at the patient level. H ow ever, the seven ity rates sim p ly have higher com p lication rates than low
m easu res collectively explained only 6% of variation in m ortality hosp itals. Althou gh ap p ealing, this hypothesis is
hosp ital m ortality rates. refu ted in part by previous stu d ies d escribing relatively
The p eriop erative p rocesses of care on w hich Su rgical w eak correlations betw een hosp itals’ com plication rates
Care Im p rovem ent Project (SCIP) and other p ay-for- and m ortality (20). In other w ord s, how hosp itals rank on
p erform ance p lans are focu sing m ay su ffer from sim ilar com p lication rates w ith a given p roced u re has little rela-
lim itations. Moreover, they relate to com p lications that tionship w ith their m ortality rates.
likely have little bearing on hosp ital m ortality rates. For An alternative explanation is that low m ortality hospi-
exam p le, p eriop erative care p rocesses highlighted by the tals and su rgeons m ay be better at rescuing patients once
SCIP have to d ate focu sed largely on su p erficial su rgical they have a com p lication, rather than at avoid ing them in
site infection and venou s throm boem bolism . Althou gh the the first p lace. N early tw o d ecad es ago, initial stud ies by
latter can be life-threatening, it only accou nts for a sm all Silber et al. su ggest that w hile com p lication incid ence rates
p rop ortion of p ostop erative d eaths. The next chap ter p ro- seem to be influ enced by p atient factors, failu re to rescue
vid es d etailed d ata show ing no association betw een hosp i- rates (the likelihood of m ortality given a com plication) are
tal com p liance w ith SCIP m easu res and su rgical ou tcom es, p red om inantly d eterm ined by hosp ital factors (20–22).
inclu d ing risk-ad ju sted m ortality, su rgical infections, and These find ings w ere confirm ed in a rigorou sly cond ucted
throm boem bolism . stu d y by Ghaferi et al., w hich u sed d etailed , clinically rich
Given the natu re of surgical care, p rocesses relating to d ata from the ACS-N SQIP (23). In this stu d y, hospitals
the op eration itself, rather than to p erioperative care, m ay w ere ranked accord ing to risk-ad ju sted m ortality and
be more im p ortant in explaining variation in outcom es. For grou p ed into qu intiles (five equ al-sized grou ps). When
exam p le, H annan et al. stud ied outcom es in 2644 p atients com p aring the “best” to “w orst” qu intiles, there w ere no
u nd ergoing carotid end arterectom y in N ew York State significant d ifferences in overall (24.6% vs. 26.9%) or m ajor
betw een 1997 and 1999. Consistent w ith prior w ork, the (18.2% vs. 16.2%) com p lication rates. H ow ever, “failu re to
investigators fou nd that high volu m e su rgeons and board - rescue” w as alm ost tw ice as high in hospitals w ith very
certified vascu lar surgeons (vs. general su rgeons and neu - high m ortality as in those w ith very low m ortality (21.4%
rosurgeons) had significantly low er rates of perioperative vs. 12.5%, p 0.001). The find ings held u p w hen stratified
stroke and d eath. H ow ever, they also id entified fou r by ind ivid u al op erations, su ch as colon resection and
processes of care strongly associated w ith patient ou t- abd om inal aortic aneu rysm rep air (Fig. 6.6).
comes: p rotam ine use, placem ent of intra-arterial shu nts Another exp lanation for the lack of hosp ital-level cor-
d u ring cross clam p, u se of eversion end arterectom y tech- relation in com p lications and m ortality is that w e have
niqu es, and u se of prosthetic patches for closing the arteri- been stu d ying the w rong com p lications. In the stu d y by
FIGURE 6.6. Rates of mortality, major Colectomy

complications, and failure to rescue at very
high and very low mortality hospitals. 25
20.5
20
17.6
Hospital Mortality
15.4 (Quintiles)
Patients (%)
15 Very low
Very high
11.4
10
5.6
5
2.5
0
Overall mortality Major complications Failure to rescue
Abdominal Aortic
Aneurysm Repair
35
Hospital Mortality
30 (Quintiles)
26.3 Very low
25 Very high
Patients (%)
20
15.5 15.6
15 13.6
10
7.3
5
3.1
0
Overall mortality Major complications Failure to rescue
Ghaferi et al. cited above, com p lications w ere chosen to variation in overall m ortality rates w as alm ost entirely
cu t across all op erations and w ere not sp ecific to ind ivid - attribu table to a single clinical event—low ou tp u t card iac
u al op erations (e.g., anastom otic leak). It is p ossible that in failu re. Rates of all other cau ses of d eath (bleed ing, stroke,
exp laining variation in ou tcom es, som e typ es of com p lica- infection, and d ysrhythm ia) w ere essentially equ ivalent
tions m atter m ore than others. For exam p le, w ith CABG, across su rgeons. Su ch d ata su ggest a sm all su bset of
O’Connor et al. had p reviou sly d escribed three-fold varia- ad verse events m ay accou nt for a d isp rop ortionate share
tion in risk-ad ju sted m ortality rates across five hosp itals in of variation in hosp ital m ortality rates and have obviou s
northern N ew England (range 2% to 6%) and six-fold vari- im p lications for qu ality im p rovem ent.
ation am ong the 18 su rgeons in this region (1.6% to 10%)
(24). To better u nd erstand sou rces of variation, the au thors
classified cau se of d eath in 384 consecu tive op erative
■ SUMMARY AND IMPLICATIONS
d eaths, based on the sem inal com p lication u ltim ately lead - While it is true that qu ality is a key d river of hosp ital varia-
ing to each p atient’s d em ise (24). In com p aring cau se-sp e- tions in ou tcom es, it is im portant to consid er the roles
cific m ortality rates across su rgeons w ith the low est and p layed by chance and patient case mix. The role of chance is
highest overall m ortality rates, they d em onstrated that particularly important when the number of cases per hospital
is sm all. N ew techniques, su ch as reliability ad ju stm ent, can 6. H alm EA, Lee C, Chassin MR. Is volu m e related to ou tcom e in health
care? A system atic review and m ethod ologic critiqu e of the literatu re.
be used to minimize statistical “noise” and prevent misla- Ann Intern Med 2002;137:511–520.
beling of su rgeons and hospitals. The role of case mix is 7. Iezzoni LI. Risk adjustment for measuring healthcare outcomes. 3rd ed .
important, bu t it is often overstated . Patient severity d oes Chicago, IL: H ealth Ad m in Press; 2003.
8. Dim ick JB, Welch H G. The zero m ortality p arad ox in su rgery. J Am Coll
not vary extensively across hospitals, and case m ix only Surg 2008;206:13–16.
explains a sm all fraction of hosp ital-level variation in ou t- 9. Dim ick JB, Welch H G, Birkm eyer JD. Su rgical m ortality as an ind icator
comes. Thus, the efficiency of quality measurement plat- of hosp ital qu ality: the p roblem w ith sm all sam p le size. JAMA
2004;292:847–851.
forms could be improved by focusing d ata collection on a 10. N orm and SL, Glickm an ME, Gatsonis CA. Statistical m ethod s for p ro-
smaller subset of the most important variables. N onethe- filing p rovid ers of m ed ical care: issu es and ap p lications. J Am Stat
less, it is im p ortant to ad ju st for these d ifferences to ensu re Assoc 1997;92:803–814.
11. H ofer TP, H ayw ard RA, Greenfield S, et al. The u nreliability of ind ivid -
fair comparisons and to prevent gaming (e.g., avoid ing the u al p hysician “rep ort card s” for assessing the costs and qu ality of care
sickest patients) of quality measurement systems. of a chronic d isease. JAMA 1999;281:2098–2105.
H ospital variation in outcomes not d ue to chance and 12. Dim ick JB, Birkm eyer JD. Ranking hosp itals on su rgical qu ality: d oes
risk-ad ju stm ent alw ays m atter? J Am Coll Surg 2008;207:347–351.
case mix can reasonably be attributed to d ifferences in qual- 13. Birkm eyer JD, Shahian DM, Dim ick JB, et al. Blu ep rint for a new
ity. A conceptu al m od el of qu ality inclu d es the relationship Am erican College of Su rgeons: N ational Su rgical Qu ality Im p rove-
betw een stru cture, process, and outcomes at d ifferent m ent Program . J Am Coll Surg 2008;207:777–782.
14. Donabed ian A. Evalu ating the qu ality of m ed ical care. Milbank Mem
phases of su rgical care. For many surgery proced ures, stru c- Fund Q 1966;44:166–206.
tural elements, such as proced ure volume, are important 15. Birkm eyer JD, Siew ers AE, Fin layson EVA, et al. H osp ital volu m e
d eterminants of outcomes. Processes of care are not w ell an d su rgical m ortality in the United States. N Engl J Med 2002;346:
1128–1137.
d eveloped in surgery and tend to relate to outcomes that are 16. Dim ick JB, Staiger DO, Baser O, et al. Com p osite m easu res for p red ict-
unim portant or extremely rare. The next chapter d iscusses ing su rgical m ortality in the hosp ital. Health Aff 2009;28:1189–1198.
several strategies for leveraging w hat is know n about varia- 17. Birkm eyer J, Stu kel T, Siew ers A, et al. Su rgeon volu m e and op erative
m ortality in the United States. N Engl J Med 2003;349:2117–2127.
tion in outcomes to improve surgical care. 18. Brad ley EH , H errin J, Elbel B, et al. H osp ital qu ality for acu te m yocar-
d ial infarction: correlation am ong p rocess m easu res and relationship
■ REFERENCES w ith short-term m ortality. JAMA 2006;296:72–78.
19. H annan EL, Popp AJ, Feu stel P, et al. Association of su rgical sp ecialty
1. H annan EL, Kilburn H Jr, O’Donnell JF, et al. Ad u lt op en heart su rgery and processes of care w ith p atient outcom es for carotid end arterec-
in N ew York State. An analysis of risk factors and hosp ital m ortality tom y. Stroke 2001;32:2890–2897.
rates. JAMA 1990;264:2768–2774. 20. Silber JH , William s SV, Krakau er H , et al. H osp ital and p atient charac-
2. O’Connor GT, Plu m e SK, Olm stead EM, et al. A regional p rosp ective teristics associated w ith d eath after su rgery. A stu d y of ad verse occu r-
stu d y of in-hosp ital m ortality associated w ith coronary artery byp ass rence and failu re to rescu e. Med Care 1992;30:615–629.
grafting. JAMA 1991;266:803–809. 21. Silber JH , Rosenbau m PR, Tru d eau ME, et al. Changes in p rognosis
3. Khuri SF, Daley J, H end erson W, et al. Risk ad ju stm ent of the p ostoper- after the first p ostoperative com p lication. Med Care 2005;43:122–131.
ative m ortality rate for the com p arative assessm ent of the qu ality of 22. Silber JH , Rosenbau m PR, William s SV, et al. The relationship betw een
surgical care: results of the N ational Veterans Affairs Surgical Risk choice of outcom e m easu re and hospital rank in general surgical proce-
Stu d y. J Am Coll Surg 1997;185:315–327. d u res: im p lications for qu ality assessm ent. Int J Qual Health Care
4. Khuri S, H end erson W, Daley J, et al. Su ccessfu l im p lem entation of the 1997;9:193–200.
d ep artm ent of Veterans Affairs’ N ational Su rgical Qu ality Im p rove- 23. Ghaferi AA, Birkm eyer JD, Dim ick JB. Variation in hosp ital m ortality
m ent Program in the private sector: the patient safety in surgery stu d y. associated w ith inp atient su rgery. N Engl J Med 2009;361:1368–1375.
Ann Surg 2008;248:329–336. 24. O’Connor GT, Birkm eyer JD, Dacey LJ, et al. Resu lts of a regional stu d y
5. Dud ley RA, Johansen KL, Brand R, et al. Selective referral to high vol- of m od es of d eath associated w ith coronary artery bypass grafting.
u m e hospitals: estimating potentially avoid able d eaths. JAMA 2000;283: N orthern N ew England Card iovascu lar Disease Stu d y Grou p . Ann
1159–1166. Thorac Surg 1998;66:1323–1328.
CHAPTER
7
Strategies for Reducing Variation
in Surgical Outcomes
J ohn D. Birkmeyer and J ustin B. Dimick
■ INTRODUCTION ■ SELECTIVE REFERRAL

As d escribed in the preced ing chapter, su rgical outcom es With this approach, payers (usually) id entify hospitals w ith
vary w id ely. In ad d ition to variation am ong ind ivid u al the best results in the selected proced ures and d irect care to
p rovid ers, (1,2) a grow ing bod y of evid ence su ggests that these facilities. Tow ard this end , they can use selective con-
risks of ad verse events after surgery vary w id ely accord ing tracting, tiered health plans, and benefits packages that give
to a nu m ber of provid er attributes, inclu d ing proced ure vol- patients financial incentives (e.g., low er co-p ays) to use pre-
ume, su rgeon subsp ecialty training, and other factors (3–5). ferred provid ers. These levers are often su pplemented w ith
Apparent variation in surgical outcomes can be attributed public reporting of volume or outcomes d ata, in the hopes
partly to chance and, to a lesser extent, to case mix differences that patients themselves w ill “shop for quality.”
across provid ers. N onetheless, there remains little d oubt that Am ong cu rrent exam p les of selective referral, the
variation in surgical outcomes also reflects real differences in Leap frog Grou p , a large coalition of p u blic and private
quality among hospitals and surgeons and thus suggests em p loyers and p u rchasers, is p rom oting “evid ence-based
substantial op portu nities for qu ality im provem ent. hosp ital referral” for seven su rgical p roced u res, based on
In resp onse, p ayers, policym akers, and professional minim u m p roced u re volu m e criteria and , for some proce-
organizations have im plem ented a variety of d ifferent d u res, risk-ad ju sted m ortality rates (10). Card iac su rgery,
strategies aim ed at red u cing variation and im proving sur- bariatric su rgery, and breast cancer care are becom ing
gical qu ality (6). Selective referral initiatives, w hich aim to increasingly popular targets for payers’ Centers of Excel-
steer su rgical patients to hospitals or su rgeons likely to have lence program s.
the best resu lts, have been p articularly popu lar am ong p ri- To d ate, su ch efforts have been effective in concentrat-
vate p ayers and p u rchaser coalitions. Other efforts are ing som e high risk p roced u res in high volu m e centers. We
instead hop ing to im prove outcom es at all hospitals, p artic- u sed national Med icare claim s d ata to assess longitu d inal
u larly those w ith su bpar resu lts. These includ e pay-for- trend s in market concentration, that is, the p rop ortion of
performance programs and “checklists” aimed at increasing total cases p erform ed in the top 10% of the bu siest hospi-
hosp ital and su rgeon com p liance w ith evid ence-based tals. While there w as little evid ence of trend s tow ard
processes related to perioperative care (7). Others are instead increased m arket concentration in card iovascular su rgery,
offering providers rigorous feed back on their outcomes rela- major cancer resections are being increasingly d irected to
tive to those of their peers, but letting hospitals and surgeons high volu me hosp itals (Fig. 7.1). With p ancreatic resection,
d etermine how to improve at the local level. Such strategies for exam p le, the p rop ortion of p atients u nd ergoing surgery
are particu larly p op u lar am ong professional organizations in very high volu m e hosp itals increased from 22% to 54%
in su rgery, in clu d in g th e Am erican College of Su rgeons betw een 1997 and 2007.
and its N ational Su rgical Quality Im provem ent Program Am ong their ad vantages, selective referral efforts often
(ACS-N SQIP) (8,9). rely on relatively sim p le stru ctu ral m easu res of qu ality
In this chap ter, w e review these three d ifferent m od els (e.g., p roced u re volu m e) and thu s can be im p lem ented
for red u cing variation in su rgical ou tcom es: selective refer- exp ed iently and inexp ensively. They also reflect the natural
ral, p rocess com p lian ce, and ou tcom es m easu rem ent. In resp onse of m any p ayers and p atients w hen confronted
ad d ition to exam ining their strengths and w eaknesses, w ith the p roblem of variation in p rovid er p erform ance
w e consid er how recent ad vances in the science of qu ality w ith su rgery. On the other hand , from the p ersp ective of
m easu rement and im p rovem ent m ight u ltim ately enhance p rovid ers, selective referral strategies are highly polariz-
the real w orld effectiveness of each strategy. (Table 7.1) ing, d ivid ing hosp itals and su rgeons into w inners and los-
ers. In alienating the latter, a p rice of selective referral may
be lost op p ortu nities for engaging p hysicians in other types
John D. Birkmeyer, Justin B. Dimick: Dep artm ent of of qu ality im p rovem ent efforts.
Surgery, University of Michigan Med ical School, Ann Arbor, A fund amental problem w ith selective referral is that it
MI 48104. is hard to know w hich hospitals and surgeons are tru ly best.
40
Chapter 7 • Strategies for Reducing Variation in Surgical Outcomes 41
Table 7 .1 Ch a ra ct er ist ics of t h r ee d iffer en t m od els for r ed u cin g va r ia t ion a n d im p rovin g

su r gica l m or t a lit y
Selective Referral Process Compliance Outcomes Measurement
Goal/mechanism Steer patients to best hospitals or Improve care in all settings by increasing Improve care in all settings by providing
surgeons hospital compliance with evidence-based feedback on surgical outcomes;
processes of perioperative care hospitals and surgeons implement
improvement efforts at local level
Examples Leapfrog Group evidence-based Surgical Care Improvement Project (SCIP), Society of Thoracic Surgery database for
hospital referral program other pay-for-performance programs cardiothoracic surgery
Payers’ Centers of Excellence Surgical checklists American College of Surgeons-National
programs in cardiac and bariatric Surgical Quality Improvement Program
surgery
Advantages Inexpensive, expedient Traction with Likely to achieve rapid improvements in Measurement alone may be effective in
patients and payers many aspects of perioperative care improving outcomes (“Hawthorne
effort”)
Disadvantages Highly polarizing (for providers) Current process measures not strongly No insights about how best to improve;
Hard to identify best providers linked with mortality and other important may limit ultimate extent of
(at individual level) outcomes improvement
Expensive
Althou gh volum e- or m ortality-based qu ality ind icators can p rocesses of care linked to im p roved su rgical ou tcomes.
reliably id entify groups of provid ers w ith better results on This m od el is p erhap s best rep resented by the ongoing
average, they d o not reliably d iscrim inate perform ance p ay-for-p erform ance p rograms of both p u blic and private
among ind ivid u als (in p art d ue to statistical pow er limita- p ayers. For exam p le, p ayers are linking hospital reim -
tions). For examp le, Krumholz et al. used clinical d ata from bu rsem ent to satisfactory ad herence to evid ence-based
the Cooperative Card iovascular Project to assess the useful- p ractices related to p eriop erative care, as d efined by the
ness of Healthgrades’ hospital ratings for acute myocard ial Su rgical Care Im p rovem ent Project (SCIP), a joint effort of
infarction (based prim arily on risk-ad ju sted m ortality rates the Centers for Med icare and Med icaid Services (CMS) and
from Med icare d ata) (11). Relative to 1-star (w orst) hosp i- the Centers for Disease Control (12). These includ e specific
tals, 5-star (best) hospitals had significantly low er mortality p rocesses aimed at red u cing rates of su rgical site infection,
(16% vs. 22%, p 0.001) after risk ad ju stment w ith clinical p ostop erative card iac events, venou s throm boem bolism,
d ata. H ow ever, the Healthgrades’ ratings poorly d iscrimi- and ventilator-associated p neu m onia.
nated among any tw o ind ivid ual hospitals. In only 3% of Long stand ard in the safety-consciou s aviation ind u s-
head -to-head comparisons d id 5-star hospitals have statisti- try, su rgical “checklists,” inclu d ing p reop erative tim e-outs,
cally low er mortality rates than 1-star hospitals. rep resent another increasingly p op u lar ap p lication of the
p rocess comp liance m od el. Their initial d issem ination in
■ PROCESS COMPLIANCE U.S. hosp itals had been m otivated p rim arily by d esires to
red u ce risks of so-called “never events,” inclu d ing w rong
Another approach to red u cing variation is to encourage site and w rong p atient su rgery. At m any centers, how ever,
hospitals and surgeons to increase their com pliance w ith su rgical checklists have been su bstantially broad ened in
clinical scop e, aim ing to red u ce m u ch m ore com m on
60 ad verse events, su ch as su rgical site infection. Interest in
50 checklists received a consid erable boost w hen a highly
p u blicized stu d y by Pronovost et al. d em onstrated their
40
Pa tie nts (%)
effectiveness in m arked ly red ucing rates of blood stream

1997
30 infections in p atients w ith central venou s lines (13).
2007
Am ong their ad vantages, p rocess com p liance strategies
20
are consid erably less p olarizing than those based on selec-
10 tive referral. In theory, anyone can “w in.” To the extent that
0
su rgeons can “p lay to the qu iz,” p rocess-based pay-for-
Bladder cancer Pancreatic cancer Lung cancer p erform ance p rogram s have the p otential to achieve rap id
and significant im p rovem ents in m any asp ects in perioper-
FIGURE 7.1. Proportion of patients undergoing cancer surgery in very high
ative care. At the University of Michigan H ospital, for
volume hospitals (as defined previously (26)), 1997 vs. 2007. Based on analysis
of national Medicare population (Nicholas Osborne, MD, personal communi- exam p le, the p rop ortion of colorectal su rgery patients
cation). receiving an ap p rop riate antibiotic w ithin 60 m inu tes prior
FIGURE 7.2. Relationship of hospital process compliance to 10.0

risk-adjusted mortality, national Medicare population.
Ris k-a djus te d morta lity ra te (%)

9.0 8.7
8.2
8.0
7.2
7.0 6.8
6.0
5.0 4.8
4.2 4.0 4.2 4.3 4.0
4.0 3.8 3.6
3.0
2.0
1.0
0.0
Corona ry a rte ry bypa s s Abdomina l a ortic Pa ncre a tic re s e ction
gra fting a ne urys m re pa ir
Ho s pitals ranke d o n pro c e s s c o mplianc e

Low Me dium High No re port
to incision increased virtually overnight, from 70% to over thesia staff d ebrief at the end of the case in ord er to exp ress
95%, follow ing im p lem entation of a pay-for-perform ance concerns related to su bsequ ent care. This intervention
program on that m easu re. Previous stu d ies in prim ary care ap p eared to be rem arkably effective. Follow ing im plem en-
su ggest that p ay-for-p erform ance p rogram s m ay be m ost tation of the checklist, overall m ortality fell by half, from
effective in im proving p rocess com pliance am ong poor 1.5% at baseline to 0.8%. Inp atient com p lications d rop ped
perform ers and thu s red u cing overall variation (14,15). from 11% to 7% after im p lem entation of the checklist.
N onetheless, the extent to w hich increased com p liance Unfortu nately, the resu lts from this stu d y seem too
w ith cu rrently targeted p rocess m easu res w ill red u ce varia- good to be tru e. Sp ecifically, it seem s im p lau sible that ou t-
tion in su rgical ou tcom es rem ains uncertain. As d escribed com es im p roved as a d irect resu lt of better com p liance
earlier, m any relate to second ary outcom es or m ay fail for w ith p rocess m easu res on their checklist. For exam ple,
other reasons to red u ce variation in m ortality across hosp i- investigators id entified a su bset of six key processes of care
tals and su rgeons. Stu d ies to d ate have generally failed to from the checklist w hose u se cou ld be d irectly verified
d em onstrate a strong relationship betw een processes tar- (e.g., p u lse oxim eter u sed , antibiotics given ap p ropriately).
geted by cu rrent pay-for-perform ance program s and out- Overall, all six ind icators w ere p erform ed in 34% of
com es. Based on d ata from the Med icare claim s files and p atients before im p lem entation of the checklist and in 57%
H ospitalCom p are, for exam ple, N icholas et al. noted w id e of p atients afterw ard s. This im p rovem ent is notew orthy,
variation in hosp ital com p liance w ith p rocess m easu res of bu t sm all relative to the observed im p rovem ents in m or-
the SCIP, ranging from 54% in the low est hospital tercile to bid ity and m ortality. More tellingly, hosp ital com pliance
91% in the highest (16). H ow ever, overall process com p li- w ith the item s on the checklist had little bearing on the
ance w as not associated w ith risk-ad justed m ortality for extent to w hich their ou tcom es im p roved . For exam ple,
any of the six p roced ures stud ied (Fig. 7.2). Moreover, com - there w ere statistically significant d eclines in both m orbid -
pliance w ith sp ecific p rocesses of care w as not associated ity and mortality at only tw o hosp itals. Im p rovem ents in
w ith low er rates of the ad verse events each w as d esigned p rocess com p liance w ere negligible at both hosp itals, how -
to m inim ize. For exam p le, hospitals w ith higher rates of ever. At the first, 94.1% and 94.2% of p atients received all
com pliance w ith venou s throm boem bolism (VTE) p rop hy- six m easu rable p rocesses before and after im p lem entation
laxis d id not have low er rates of VTE. of the checklist, resp ectively. Process com p liance w as 0%
In contrast to the nu ll stu d ies of p ay-for-p erform ance d u ring both tim e p eriod s at the other hosp ital. These
program s, a recent stu d y p ublished in the New England resu lts su ggest that overall m orbid ity and m ortality
Journal of Medicine su ggested that p rocess com p liance d eclined becau se of other, u nm easu red changes in practice
strategies m ay be m ore effective in the form of intraop era- ind u ced by this stu d y, not as a d irect resu lt of com p liance
tive checklists. H aynes et al. stu d ied perioperative ou t- w ith the targeted p rocesses.
com es before and after im plem entation of a 19-item
checklist in 3733 p atients u nd ergoing noncard iac su rgery
at eight hosp itals arou nd the w orld (7). Specific item s
■ OUTCOMES MEASUREMENT
includ ed several pertaining to patient verification (nam e, In contrast to payers, professional organizations in surgery
proced u re, site, and allergies) and team prepared ness (e.g., are focu sing p rimarily on d isseminating nationw id e sys-
availability of necessary equ ipm ent, im aging tests). The tem s for tracking su rgical ou tcom es. Their goal is to provid e
checklist also requ ired that the su rgeon, nursing, and anes- hospitals and surgeons w ith rigorous feed back about their
Chapter 7 • Strategies for Reducing Variation in Surgical Outcomes 43
outcomes relative to their peers, in the hopes that they w ill With advances in both quality measurement and improve-
id entify opportu nities for im provem ent and respond ment, the effectiveness of each strategy cou ld be enhanced
accord ingly. This mod el is less prescrip tive than the Process consid erably. Selective referral strategies w ou ld benefit
Com pliance ap proach and assumes that hospitals and su r- m ost from the d evelop m ent of m easu res that better d is-
geons can d ecid e best how to improve care at the local level. crim inate p erform ance am ong p rovid ers and better fore-
The Society of Thoracic Surgeons w as among the first to cast ou tcom es. As d escribed in the p reviou s chap ter,
em brace this m od el and now the large m ajority of U.S. hos- reliability ad ju stm ent is essential for m inim izing the d istor-
pitals involved in card iac surgery contribu te to its national tion of p rovid er-sp ecific ou tcom e m easu res by statistical
outcomes d atabase (17). First d eveloped by the Departm ent noise and is argu ably m ore im p ortant than risk ad ju st-
of Veterans Affairs, the N ational Surgical Quality Improve- m en t. The d evelop m en t and ap p lication of com p osite
ment Program (N SQIP) has been ad apted for use in the pri- m easu res—su m m ary m easu res of p erform ance that incor-
vate sector by the American College of Surgeons (ACS) and p orate inform ation from m u ltip le d om ains of quality—w ill
has grad ually becom e the m ost recognized ou tcom es m eas- also be essential in p rovid ing p atients, p hysicians, and
urement platform for noncard iac surgery. other stakehold ers w ith better inform ation abou t relative
This m od el of centralized ou tcom es m easu rem ent bu t p erform ance (17,20,21). Sim p le com p osite measu res com -
local, im p licit qu ality im provem ent has particular ap p eal bining volu m e and m ortality d ata are far su p erior in p re-
among su rgeons. They view good ou tcomes as the best cri- d icting fu tu re ou tcom es than either alone—p articu larly
terion of su rgical quality, but d o not like d irectives abou t for less com m on p roced u res (22). More com p lex com -
how to achieve them . There is strong evid ence that this p osite m easures that incorporate ou tcom es from related
mod el can be very effective in red ucing both overall m or- p roced u res are even better p red ictors of hosp ital ou tcomes
tality and variation across p rovid ers. In northern N ew Eng- (23). In ad d ition to im p roving the u nd erlying m easu res,
land , for exam p le, m ortality w ith coronary artery byp ass broad er access to p rovid er-sp ecific p erform ance d ata w ill
grafting (CABG) fell by m ore than 25% alm ost im m ed iately be essential in enhancing the effectiveness of selective refer-
follow ing feed back of m ortality d ata to hospitals and su r- ral strategies. At the present time, the most rigorous and
geons; variation in m ortality rates across hospitals fell even most d etailed sources of surgical outcomes d ata are kept
more d ram atically (18). This su rgical “H aw thorne effect” confid ential by p rofessional organizations, includ ing the
has been sim ilarly observed in Veterans Affairs hospitals ACS and the Society of Thoracic Su rgeons, and not m ad e
nationw id e after im plem entation of N SQIP. Althou gh w hat p u blicly available.
actu ally changed about clinical practice to effect this Im proving the effectiveness of p rocess com pliance
im p rovem ent has not been characterized , overall m orbid - strategies w ill requ ire higher leverage p rocesses on w hich
ity rates fell by over 40% (19). to base them . Cu rrent p ay-for-p erform ance p rogram s and
Am ong their d isad vantages, outcom es m easu rem ent checklist initiatives are bu ilt arou nd p eriop erative p ractices
program s often involve extensive d ata collection (in p art to that are linked only w eakly to ou tcom es; they vary little
ensure ad equ ate risk ad justm ent) and thus can be expen- across hosp itals or are related to second ary ou tcom es.
sive. For exam p le, annu al costs for hosp itals particip ating Ongoing efforts are also focu sed alm ost exclu sively on p re-
in ACS-N SQIP exceed $100,000. As d escribed earlier, ou t- venting comp lications in the first p lace. As im plied in the
com e m easures are often hind ered by sm all sam ple sizes p reviou s chap ter, how ever, p rocesses that im prove the
that are too “noisy” to inform hosp itals and su rgeons of tim ely recognition and m anagem ent of com p lications once
their tru e p erform ance. Finally, unless linked to informa- they have occu rred m ay be even m ore im p ortant in red u c-
tion abou t p rocess, outcom es m easu rem ent provid es no ing variation in hosp ital m ortality rates. In a sem inal stud y
insights abou t best practices and how ind ivid ual provid ers by Ghaferi et al. exam ining reasons for variation in surgical
or the p rofession as a w hole can im p rove. m ortality rates, (24) high mortality hosp itals had sim ilar
com p lication rates as other hosp itals, bu t w ere d istin-
guished prim arily by m u ch higher m ortality rates after
■ TOWARD MORE EFFECTIVE STRATEGIES com p lications—so-called failu re to rescu e.
Selective referral, process com pliance, and ou tcomes m eas- Finally, the ou tcom es m easu rem ent m od el w ould bene-
urem ent reflect d ifferent philosophies on how best to fit by m ore exp licit and effective strategies for qu ality
im prove su rgical qu ality and have d istinct ad vantages and im p rovem ent. As a start, the m ajor su rgical outcom es reg-
d isad vantages. As d escribed elsew here, (6) the op tim al istries should begin inclu d ing m ore inform ation about
strategy m ay d ep end on both the clinical context and p olit- p rocess of care and p lace greater em p hasis on u nd erstand -
ical realities. For exam ple, selective referral m ay be the ing emp irical relationship s betw een processes and ou t-
most exp ed ient and effective strategy for red u cing varia- com es. As it evolves tow ard p roced u re-sp ecific qu ality
tion in ou tcom es for a su bset of p articu larly high risk bu t m easu res, the new ACS-N SQIP w ill be collecting inform a-
uncom m on p roced ures (e.g., esophagectom y and p ancrea- tion abou t not only general p eriop erative care, bu t
tectom y), bu t this approach w ill likely rem ain p olitically also techniqu e and other p ractices u niqu e to ind ivid u al
untenable for p roced u res im plying the red istribu tion of op erations (25). It hop es to red u ce variation in both
large nu m bers of patients. p rocesses and ou tcomes by id entifying and d issem inating
best p ractices. Second , “closing the loop ” on qu ality 11. Kru m h olz H M, Rath ore SS, Chen J, et al. Evalu ation of a consu m er-
orien ted in tern et h ealth care rep ort card : th e risk of qu ality ratin gs
im provem ent w ould be facilitated by the form ation of based on m ortality d ata. JAMA 2002;287(10):1277–1287.
regional- and state-level collaboratives, like the Michigan 12. Gold JA. The surgical care im p rovem ent p roject. WMJ 2005;104(1):
Su rgical Qu ality Collaborative d escribed elsew here in this 73–74.
13. Pronovost PJ, N eed ham D, Berenholtz S, et al. An intervention to
ed ition. While there are obviou s ad vantages associated w ith d ecrease catheter-related blood stream infections in the ICU. N Engl J
national stand ard s for quality m easu rem ent, im provem ent Med 2006;355:2725–2732.
occurs locally and can be greatly accelerated w hen surgeons 14. Rosenthal MB, Dud ley RA. Pay-for-p erform ance: w ill the latest p ay-
m ent trend im prove care? JAMA 2007;297(7):740–744.
collaborate and share insights. 15. Rosenthal MB, Frank RG, Li Z, et al. Early exp erience w ith p ay-for-
perform ance: from concep t to p ractice [see com m ent]. JAMA 2005;
■ REFERENCES 294(14):1788–1793.
16. N icholas LH , Osborne N H , Birkm eyer JD, Dim ick JB. H osp ital p rocess
1. H annan EL, Kilbu rn H Jr, O’Donnell JF, et al. Ad u lt op en heart su rgery com p liance and surgical ou tcom es am ong Med icare p atients. Arch Surg
in N ew York State. An analysis of risk factors and hosp ital m ortality 2010;145(10):999–1004.
rates. JAMA 1990;264(21):2768–2774. 17. Shahian DM, Ed w ard s FH , Ferraris VA, et al. Qu ality m easu rem ent in
2. O’Connor GT, Plum e SK, Olm stead EM, et al. A regional p rospective ad u lt card iac su rgery: p art 1–concep tu al fram ew ork and m easu re
stu d y of in-hosp ital m ortality associated w ith coronary artery byp ass selection. Ann Thorac Surg 2007;83(4 Su p p l):S3–S12.
grafting. JAMA 1991;266:803–809. 18. O’Connor GT, Plum e SK, Morton JR, et al. Resu lts of a regional
3. Du d ley RA, Johansen KL, Brand R, et al. Selective referral to high vol- prospective stu d y to im prove the in-hosp ital m ortality associated w ith
u m e hospitals: estim ating p otentially avoid able d eaths. JAMA 2000; coronary artery byp ass grafting. JAMA 1996;275:841–846.
283:1159–1166. 19. Khu ri SF, Daley J, H end erson WG. The com p arative assessm ent and
4. H alm EA, Lee C, Chassin MR. Is volu m e related to ou tcom e in health im p rovem ent of qu ality of su rgical care in the Departm ent of Veterans
care? A system atic review and m ethod ologic critiqu e of the literature. Affairs. Arch Surg 2002;137(1):20–27.
Ann Intern Med 2002;137:511–520. 20. N orm and SL, Glickm an ME, Gatsonis CA. Statistical m ethod s for p ro-
5. H ou ghton A. Variation in ou tcom e of su rgical p roced u res. Br J Surg filing provid ers of m ed ical care: issu es and ap p lications. J Am Stat
1994;81:653–660. Assoc 1997;92:803–814.
6. Birkm eyer N J, Birkm eyer JD. Strategies for im p roving su rgical qu ality– 21. N orm and SL, Shahian DM. Statistical and clinical asp ects of hosp ital
shou ld p ayers rew ard excellence or effort? N Engl J Med 2006; ou tcom es p rofiling. Stat Sci 2007;22:206–226.
354(8):864–870. 22. Dim ick JB, Staiger DO, Baser O, et al. Com p osite m easu res for p red ict-
7. H aynes AB, Weiser TG, Berry WR, et al. A su rgical safety checklist to ing su rgical m ortality in the hosp ital. Health Aff 2009;28:1189–1198.
red uce m orbid ity and m ortality in a global p op u lation. N Engl J Med 23. Staiger DO, Dim ick JB, Baser O, et al. Em p irically d erived com p osite
2009;360:491–499. m easu res of su rgical perform ance. Med Care 2009;47:226–233.
8. Fink A, Cam p bell DJ, Mentzer RJ, et al. The N ational Su rgical Qu ality 24. Gh afer i AA, Birkm eyer JD, Dim ick JB. Variation in h osp ital m or-
Im p rovem en t Program in n on -veteran s ad m in istration h osp itals: tality associated w ith inp atient su rgery. N Engl J Med 2009;361;
initial d em onstration of feasibility. Ann Surg 2002;236:344–353. 1368–1375.
9. Row ell KS, Turrentine FE, H u tter MM, et al. Use of national su rgical 25. Birkm eyer JD, Shahian DM, Dim ick JB, et al. Blu ep rint for a new
qu ality im p rovem ent p rogram d ata as a catalyst for qu ality im p rove- Am erican College of Su rgeons: National Su rgical Quality Im provem ent
m ent. J Am Coll Surg 2007;204:1293–1300. Program . J Am Coll Surg 2008;207:777–782.
10. Birkm eyer JD, Dim ick JB. Potential benefits of the new Leap frog stan- 26. Birkm eyer JD, Siew ers AE, Finlayson EVA, et al. H osp ital volu m e and
d ard s: effects of p rocess and ou tcom e m easu res. Surgery 2004;135: su rgical m ortality in the United States. N Engl J Med 2002;346:
569–575. 1128–1137.
CHAPTER
8
Building Successful Quality
Improvement Collaboratives
Michael J . Englesbe
Recent w ork in su rgical health services clearly ind icates of frank d iscu ssion of su rgical com p lications in m orbid ity
broad variation in clinical outcom es throu ghout the United and m ortality conferences. Thou gh su ch sharing w ithin
States (1–8). Variation in ou tcom es im plies opp ortu nities institu tions is critical, these efforts are lim ited by institu-
for im p rovem ent. Significant efforts have been m ad e to tional hierarchy and local p ractice biases. Collaboratives
better u nd erstand these variations in an effort to im p rove involving m u ltiple institu tions can overcom e these lim ita-
qu ality. Im p roving surgical qu ality means red u cing both tions and have been show n to be effective. The potential of
postop erative m ortality and com plications. Surgical com - a su rgical qu ality collaborative w as introd u ced by the w ork
plications have p articu larly been the focus of recent efforts of O’Connor w ithin the N orthern N ew England Card iovas-
becau se they are relatively com m on and are exp ensive for cu lar Disease Stu d y Grou p (6). Collaboration am ong health
hosp itals and p ayers (9–12). Accord ing to one recent w ork, services researchers and card iac su rgeons throu ghou t N ew
major com plications follow ing general and vascular sur- England resu lted in a rem arkable red u ction in variation in
gery ad d over $11,000 to the baseline costs of an elective ou tcom es as w ell as overall red u ctions in m ortality. This
surgical p roced u re (11). In ad d ition, health care p u rchasers, w ork has lead to nu m erou s other qu ality collaboratives,
such as large em p loyers, have a vested interest in red u cing m any of w hich rep ort im p ressive resu lts (3,5,19–23). In
surgical com p lications, in an effort to red uce costs and op ti- Michigan, w e p articip ate in the Michigan Su rgical Qu ality
mize em p loyee p rod u ctivity. Most im portantly, all p atients Collaborative (MSQC). This collaborative fu nctions on the
d eserve the highest quality of care possible. fram ew ork of the Am erican College of Su rgeons-N ational
Unfortu nately, there is no sim ple explanation for the Su rgical Qu ality Im p rovem ent Program (ACS-N SQIP).
broad variation in ou tcom es, and as a resu lt, there is no This collaborative of 34 hosp itals w ithin Michigan has
sim p le target for im proving su rgical qu ality. Both p ayers yield ed som e im pressive early resu lts w ith a significant
and p u rchasers have attem pted variou s strategies to red u ction in su rgical com p lications rates w ithin the state
im p rove su rgical ou tcom es. For exam ple, some p rivate (24). (Fig. 8.1)
payers selectively refer p atients for com plex su rgery, su ch Overall, m ost su ccessfu l qu ality collaboratives have
as transp lantation or m ajor cancer su rgery. Similarly, the been regional in natu re. In ad d ition, they are bu ilt u p on
Leapfrog Group uses strategies of both selective referrals regional clinical strengths and p ersonal relationship s.
and p u blic rep orting to try to encou rage patients to seek N onetheless, there are nu merou s p otential m od els for a
high qu ality hospitals (13,14). N ew er program s, w hich su rgical qu ality collaborative, each u niqu e to the partici-
seem ed favored by p ublic insu rers, inclu d e variou s valu e pants. In this chapter, we w ill highlight four key components
base p u rchasing program s, such as pay-for-perform ance to build ing a successful quality collaborative (Fig. 8.2). We
ones. In these p rogram s physicians or hospitals are incen- w ill then briefly highlight som e highly su ccessfu l collabo-
tivized to m eet sp ecific ou tcom e or p rocess of care bench- ratives in su rgery. Finally, w e w ill d etail ou r exp erience
marks. Whether su ch strategies w ill lead to significant w ith the MSQC in Michigan.
im p rovem ents in qu ality or costs rem ains u nclear (15,16).
Qu ality collaboratives are another ap p roach to red u ce
su rgical com p lications. Collaboratives fu nction on a com - ■ A BUSINESS CASE FOR QUALITY
m u nity of p ractice fram ew ork. This fram ew ork em p ha- IMPROVEMENT
sizes the im p ortance of m u tu al sharing and learning
betw een health care professionals in an effort to d evelop Cu rrently, cost red u ction is a focu s of health care reform.
effective ap p roaches to care im provement (17,18). Su rgical The United States sp end s ap p roxim ately 70% m ore for
qu ality collaboratives build u pon long-stand ing trad itions health care, as a p ercentage of Gross Dom estic Prod uct,
than d o m ost d evelop ed cou ntries (25). Desp ite this, m any
exp erts claim that Am ericans d o not get higher qu ality
Michael J. Englesbe: University of Michigan H ealth Sys- health care. This observation has fu eled broad based
tem, 2926 Tau bm an Center, 1500 E Med ical Center Drive, Ann m om entu m to im p rove qu ality, w hile at the sam e tim e
Arbor, MI 48109. red u ce costs. Within this context, it is critical to consid er the
45
FIGURE 8.1. Shewart control-chart demonstrating MS QC O/E Ratio Co ntro l Chart fo r Mo rbidity
changes in the Michigan Surgical Quality Collabora-
tive (MSQC) observed to expected morbidity rates (O/E
ratio) over time. The observed morbidity rates are P roce s s Cha nge
1.4
adjusted for patient characteristics. The expected No
morbidity rates are calculated based on a national Yes
sample from the ACS-NSQIP. (• represents a process
change where a run of eight or more points are on one
side of the center line). 1.2 S igma leve l:
3
O/E Ratio
1.0
0.8
0.6
JAN 05
MAR 05
MAY 05
J UL 05
S EP 05
NOV 05
JAN 06
MAR 06
MAY 06
J UL 06
S EP 06
NOV 06
JAN 07
MAR 07
MAY 07
J UL 07
S EP 07
NOV 07
potential qu ality im p rovem ent and cost im p lications of any claim s d ata, lim ited p rim ary d ata collection, and a highly
initiative to im prove care. selective case m ix. Thou gh SCOAP is m ore lim ited in its
Qu ality collaboratives can be exp ensive. For exam - bread th, this highly focu sed collaborative fu nctions at a
p le, th e ACS-N SQIP (coverin g only general and vascu lar sm all fraction of the costs of the ACS-N SQIP.
su rgery) costs p articip atin g institu tions ap p roxim ately Participation in quality improvement initiatives, whether
$135,000 p er year (26,27). This includ es the costs of d ata- voluntary or required , can become overw helming for hospi-
base m anagem ent, statistical analysis, d ata collection, and tals. N umerous state and fed eral agencies have significant
aud iting for d ata accu racy. The collection of high qu ality d ata collection and reporting requirements w hich occupy
clinical d ata requ ires a highly trained ind ivid u al, and in the su bstantial hosp ital resou rces. In ad d ition, hosp itals are
case of the ACS-N SQIP, this is generally a full-tim e nu rse invited to p articip ate in nu m erou s volu ntary qu ality
review er. H igh qu ality d ata d oes have significant valu e for im p rovem ent initiatives. Particip ation requ ires resou rces
a collaborative. First, it provides robust risk-adjusted center- and as a resu lt hosp itals m u st carefu lly consid er the p oten-
sp ecific ou tcom es. Second , it facilitates su rgeon tru st in tial return on the investment for each quality improvement
rep orted ou tcom es. In contrast to the ACS-N SQIP, other program. If a surgeon feels strongly about a quality improve-
qu ality collaboratives have d eveloped highly efficient and ment initiative, he or she must communicate the potential
inexpensive d ata collection m ethod ologies (3,26,28). For clinical benefits to hospital ad ministrators. In ad d ition, the
exam p le, in the state of Washington, the Su rgical Clinical surgeon must w ork closely w ith hospital officers to d evelop
Ou tcom es Assessm ent Program (SCOAP) relies u p on a viable business plan for participation.
Within this context, there is a significant am ou nt of d ata
that rep orts the financial benefits of qu ality im p rovem ent
for both p ayers and hosp itals in the United States (9–12).
Und erstand ing this relationship requires a brief d escrip -
tion of how hosp itals are generally p aid for su rgery. A high
p rop ortion of the costs of su rgery are from p aym ents to
hospitals for the proced u re-specific d iagnosis related
grou p (DRG). DRG p aym ents w ere d evised u nd er the
Prosp ective Paym ent System to bu nd le p aym ents for hos-
p itals for the care of a p atient w ith a p articu lar d iagnosis.
This DRG p aym ent can generally be ad ju sted for illness
severity and / or case com p lexity. The DRG p aym ent sys-
tem is u sed by Med icare and m any large p rivate p ayers.
Im p ortantly, hosp itals m ay receive ad d itional p aym ents
FIGURE 8.2. Key components to a successful surgical quality collaborative. for read m issions and ou tlier p aym ents, both of w hich are
Chapter 8 • Building Successful Quality Improvement Collaboratives 47
Medicare payments for adverse events following major surgery ers look favorably u pon centers w ith a com mitment to
qu ality im p rovem ent and cost red u ction. In ad d ition, vol-
$40,000 u ntary p rogram s in qu ality im p rovem ent m ay red u ce third
p arty regu lation and oversight. Characterization of relative
p atient acu ity and exem p lary ou tcom es p rovid e leverage
Medicare Payments
for hosp ital ad m inistration w hen negotiating w ith insu r-

ance com p anies.
$20,000 On a m ore granu lar level, both the hosp ital and the pay-
ers have a financial stake in su rgical com p lications. With
resp ect to colectom y, ou r grou p has evalu ated the financial
im plications of su rgical com plications for ou r institu tion
and for a large p rivate p ayer. We note that a com plication
$- follow ing colectom y is associated w ith $12,137 of ad d i-
CABG LEBG Colectomy
tional reim bu rsem ent to the hosp ital (p ayer costs) w hile a
DRG Outlier Readmission
com p lication is associated w ith $20,486 of ad d itional costs
FIGURE 8.3. Medicare payments for major surgery (MEDPAR 2002). Mean to the hosp ital (Table 8.1) (11). As a resu lt, the hospital loses
hospital payments for the surgical event (within 30 days of the operation or
during the initial hospital admission) are classified into DRG payments, outlier $8,349 in p rofit on colectom y cases w ith a com plication.
payments, and payments for readmissions within 30 days of the surgical Fu rther, the hosp ital actu ally has a negative financial m ar-
event. CABG, coronary artery bypass grafting; LEBG, lower extremity bypass gin of $1460 on colectom y cases that involve a com plica-
grafting.
tion. Sim ilar financial relationship s betw een hospital
m argin, p ayer reim bu rsem ent, and su rgical com plications
have been noted follow ing kid ney transp lantation, liver
associated w ith ad verse outcom es. Med icare id entifies ou t- transp lantation, and hep atobiliary su rgery (10,29).
lier cases by com paring the estim ated costs for the case to a The d evelop m ent of a su ccessfu l qu ality collaboration
fixed loss threshold that is specific to the case DRG. Once a requ ires carefu l consid eration of finances. This inclu d es
case qu alifies as an outlier, the hospital is reim bu rsed as a the costs of ad m inistering the p rogram in ad d ition to the
fixed p ercentage of su bm itted charges. Outlier p aym ents p otential cost savin gs associated w ith qu ality im p rove-
and p ayments for 30-d ay read m issions can represent a sig- m en t goals. This retu rn on investm en t an alysis m u st be
nificant p roportion of total paym ents for a su rgical event. d one p rior to initiating a collaborative. Both clinical and
(Fig. 8.3) For exam ple, w hen only consid ering coronary fin an cial ben ch m arks m u st be con sid ered as th e collabo-
artery byp ass grafting (CABG), low er extrem ity byp ass ratives p rogresses (26,30). Frequ ent rep orting of quality
grafting, and colectom y, Med icare paid hospitals $1.5 bilim provem ent as w ell as cost savings w ill facilitate ongoing
lion in ou tlier p aym ents and 30-d ay read m issions p ay- financial su p p ort for the collaboratives and opportunities
ments in 2002. Ad d itional sou rces of paym ent p otentially for exp ansion.
related to su rgical com p lications inclu d e p aym ent for In the d evelop m ent of the MSQC, the need for carefu l
home health and nursing hom e care. Little is know n abou t consid eration of the costs im p lications w as ap p reciated
how m u ch these sources of paym ents contribute to the total early in the p rocess. As m entioned , the MSQC w as created
costs of surgery. on the fou nd ation of the ACS-N SQIP. Participation w as
Im p rovem ents in qu ality are associated w ith financial fu nd ed by Blu e Cross Blu e Shield Michigan/ Blu e Care
incentives for hospitals. Few er surgical com p lications N etw ork (BCBSM). The officers of BCBSM w ere w hole-
resu lt in shorter length of stay. Prolonged bed occu p ancy is hearted ly engaged in efforts to im prove the care of
associated w ith significant opportu nity costs for hosp itals, p atients. N onetheless, they m ad e it very clear that any
as bed tu rnover is profitable for hospitals. Insurance carri- broad clinical initiative w ou ld be carefu lly scrutinized by
Table 8 .1 Th e fi n a n cia l im p lica t ion s of su r gica l com p lica t ion s follow in g

colon su r ger y for t h e p ayer a n d t h e h osp it a l (11) a
Hospital Profit:
Course Following Reimbursement (Reimbursements
Colectomy to Hospital Hospital Costs Minus Costs)
Complications $34,490 $35,950 ($1,460)
No complications $22,353 $15,464 $6,889
Change in reimbursement $12,137 Loss in profit ($8,349)
a
Note that not only does the payer have increased costs following complications, but the hospital loses profit and actually has a
negative financial margin following colectomy cases with surgical complications.
their large clients (su ch as General Motors). As a resu lt, at of high qu ality d ata is exp ensive. H osp itals collect large
the initiation of the MSQC, specific quality im p rovem ent am ou nts of d ata, som e of w hich are qu ite reliable, as
(QI) goals w ere established in ord er to assu re that BCBSM requ irem ents for other m and atory rep orting m echanism s.
w ou ld have a reasonable financial retu rn on the invest- Qu ality collaboratives that take ad vantage of som e of this
ment. More sp ecifically, w e d eterm ined that if the MSQC d ata collection can p otentially fu nction w ith m u ch low er
could achieve a 1.8% red u ction in com plications per year costs (27).
over a 3-year p ilot p rogram , BCBSM w ou ld fu lly recou p Analytic m ethod s u sed w ithin a collaborative mu st be
the $5 m illion investm ent in the program (26). Based on valid and broad ly accep ted in ord er to ensu re that p artici-
previou s exp eriences w ith the ACS-N SQIP, ou r goal w as a p ants feel accou ntable for rep orted ou tcom es. A frequ ently
3% red u ction in com plications over the 3-year pilot p ro- rep orted anecd ote involving inad equ ate d ata analysis
gram (31). If w e had achieved this clinical goal, w e calcu - involves card iac su rgery in the state of N ew York (4,34,35).
lated a $2.5 m illion savings to BCBSM. Im portantly, as the When the state began releasing, and new sp ap ers began
initial hosp itals that joined the MSQC reached their third p u blishing, u nad ju sted m ortality rates follow ing heart sur-
year of participation, the program has significantly exceeding gery for hosp itals w ithin N ew York State, it had a profou nd
the prop osed qu ality im provem ent benchm arks. Becau se effect on p atients, su rgeons, and hosp itals. To the u niniti-
of this excellent com m u nication betw een the MSQC lead erated , a higher p ercent m ortality w as bad , and a low er p er-
ship and BCBSM, both clinical and financial goals are centage w as good . Bu t the raw p ercentages left out any
clearly stated and aligned . consid eration of the involved p atient p op u lation, som e-
thing of no sm all nu ance to su rgeons. At that tim e, there
w as no system for statistical covariate ad ju stm ent in p lace.
■ STANDARDIZED DATA INFRASTRUCTURE N ot only d id surgeons not feel accou ntable for these ou t-
Particip ants in a collaborative m u st feel accou ntable for com es, bu t the p u blic rep orting of these d ata had long-term
their hosp ital’s ou tcom es d ata. Su rgeon and nurse p artici- and p rofou nd effects, both good and bad , on fu tu re qu ality
pants d rive the qu ality im p rovem ent w ithin their institu - im provem ent efforts.
tions. The collaborative provid es a bou nty of p otential Clearly, the analytic m ethod s u sed in a qu ality collabo-
qu ality imp rovem ent initiatives for each institution. Within rative m u st be broad ly accep ted by all m em bers of the col-
this context, it is p aram ount that surgeons w ithin the collaborative. This can be a challenge consid ering the d iverse
laborative tru st both the analytic and d ata collection m eth- backgrou nd of m em bers of the collaborative. Method olo-
od s. When faced w ith poor ou tcom es, surgeons and gies m ust be und erstood not only by the sm all num ber of
hospitals frequently w ill assum e that this is related to case su rgeons and analysts overseeing the ou tcom es rep orting,
mix com plexity w ithin their institution or problem s w ith bu t also by the nu rses and su rgeons p articip ating in the
d ata. For exam p le, at the University of Michigan w e collaborative. The m ajority of these ind ivid u als w ill have
assu m ed that ou r high rates of su rgical site infection (SSI) no exp ertise in health services research. In short, collabora-
w ere related to the fact that w e had the m ost obese p atients tive p articip ants m u st tru st the d ata and the ind ivid u als
in Michigan. When w e looked at the d ata, ou r p atients overseeing d ata m anagem ent. As has been d iscu ssed else-
w ere actu ally slightly thinner than the average p atient at w here, this observation favors a locally based collabora-
other institu tions. With this observation it becam e clear to tive. In ad d ition, it also favors an ad m inistrative and
us that excu ses for high SSI rates w ere no longer app rop ri- analytic infrastru ctu re of the collaborative rooted in su r-
ate, and action w as aggressively taken, w ith rem arkable geon m em bers, not p ayers or nonsu rgeon researchers.
su ccess. Overall, fair m etrics of accou ntability are critical. With a
Clinical ou tcom es d ata shared w ithin a collaborative fou nd ation of strict d efinitions, rigorou s d ata collection,
essentially d rive the agend a of the collaborative. As m en- and stand ard ized end p oints, a reliable p red ictive m od el
tioned p reviou sly, high qu ality d ata can be com plex and for ou tcom es can be d evelop ed . Im p ortantly, operations
expensive to collect. This is particu larly true w hen collect- that are com p ared betw een hosp itals m u st be relatively
ing d ata on clinically com plex ou tcom es such as surgical com m on, w ith relatively high rates of com p lications, other-
com plications. When d eterm ining the d ata to be collected w ise reliable com p arisons are not p ossible d u e to inad e-
for a QI initiative, carefu l consid eration m u st be given to qu ate statistical p ow er (36). Within this context, the
the d efinition of the comp lication. Significant w ork has collaborative shou ld focu s on hosp ital-level ou tcom es and
been d one on this issu e by other group s (32,33). This d ata not su rgeon-level ou tcom es. Su rgeon-level ou tcom es are
mu st be collected by a highly trained ind ivid u al, usu ally a d ifficu lt to reliably m easu re, and focu sing on these out-
nu rse w ith significant clinical experience. Data collection com es m ay alienate p articip ants (37,38).
mu st be aud ited to ensu re accu racy across participating
hospitals. Consid ering the efforts required to ensu re high
qu ality d ata collection, d etermination of specific variables
■ SURGEON LEADERSHIP
for collection m u st be carefully consid ered . In ad d ition, col- Lead ership of qu ality collaboratives is critical. The lead er-
lection of any new d ata m u st be tested to ensu re accu racy ship of the collaborative need s exp ertise and clinical
before w id esp read rollou t. Unfortu nately, the collection cred ibility. In short, the collaborative need s to be led by a
surgeon. Thou gh supp ort from nurses, statisticians, and tive. For exam p le, m u ch of the lead ership of the MSQC,
health services researchers is im portant, su rgeons are less and a similarly form atted collaborative w ithin Tennessee,
likely to actively participate in collaboratives led by these came from the lead ership of the state chap ter of the ACS.
ind ivid u als. Every su rgeon know s the im p ortance of clini- These ind ivid u als had know n each other for a long tim e
cal cred ibility w hen trying to influ ence the opinions of and alread y had a m u tu ally resp ectfu l and collegial rela-
other surgeons. Influential surgeons are generally respected tionship . In all, local p rofessional societies p lay an im por-
in the op erating room . Overall, collaborative lead ership by tant role in the genesis of regional qu ality collaboratives.
a single or a sm all grou p of prom inent senior su rgeons,
thou gh not m and atory, has m any ad vantages.
Collaboratives generate id eas for qu ality im p rovem ent.
■ SUCCESSFUL QUALITY COLLABORATIVES
The inform ation d issem inated at the collaborative m u st be Trad itionally in su rgery, clinical im p rovem ents in care have
not only ap p reciated bu t im plemented . Im plem entation of com e from w eekly m orbid ity and m ortality conferences.
im provem ent initiatives w ithin hosp itals can be challeng- Du ring these interactive m eetings, cases are p resented and
ing. Som e of the su ccess of the MSQC is likely related to clinicians d iscu ss clinical d ecision-m aking, technique, and
the fact that p articip ating su rgeons are senior institu - relevant clinical literatu re. Thou gh not often consid ered
tional lead ers. More sp ecifically, m ost of the p articip ating collegial, the strengths of su ch conferences inclu d e face-to-
su rgeons lead the d ep artm ent of su rgery w ithin their face com m u nication and broad u nd erstand ing of p rocesses
hosp itals. These ind ivid u als are w ell su ited to influ ence of care w ithin an institu tion. Thou gh su rgeons w ere the
im p ortant initiatives at their institu tion. As w e d evelop ed first to have regu lar stru ctured qu ality im provem ent efforts
the MSQC, there w as som e concern about too mu ch senior su ch as these, in recent years it has becom e clear that ad d i-
su rgeon p articip ation. We w ere w orried that the senior tional efforts are need ed . This realization w as fu eled pri-
su rgeons w ou ld be less op en to sharing ou tcom es and m arily by the observation that there w as broad variation
m ore resistant to change. Fortu nately, this has not been the across hosp itals in ou tcom es, ind icating significant oppor-
exp erience. tu nity for im p rovem ent (4–6,39). Within this context,
nu m erou s su rgical qu ality collaboratives have been d evel-
op ed . We w ill briefly d iscu ss three highly su ccessfu l collab-
■ Collegial atmosphere oratives.
It is im p erative that su rgeon lead ers of the collaborative set
a tone of collegiality. We all know that local su rgical m ar- ■ Northern New England Cardiovascular
kets can be com petitive. Within the MSQC, there w as an
Disease Study Group
early ap preciation for the d eleteriou s im p act of potential
com p etition am ong surgeons and institu tions. This w as Am ong the first groups to recognize the pow er of regional
ad d ressed at the onset w ith all potential particip ants. The collaboration w as the N orthern N ew England Card iovas-
MSQC by-law s state that any institu tion u sing MSQC ou t- cular Disease Stud y Group (6). Starting in 1987, this remark-
com e d ata for com petitive ad vantage w ill be expelled from able group attempted to d etermine w hether an organized
particip ation. Similarly, every effort m ust be m ad e to facili- intervention inclu d ing d ata feed back, site visits, and con-
tate a com fortable environm ent for sharing outcom es, both tinu ou s qu ality im provem ent efforts w ould im prove hos-
good and bad . This requ ires trust in the lead ership and p ital m ortality rates follow ing CABG. This stu d y inclu d ed
other m em bers of the collaborative. It also requires tru st in 23 card iac su rgeons in Maine, Verm ont, and N ew H am p-
d ata confid entiality. For exam p le, thou gh the MSQC is shire and resu lted in a 24% red u ction in hosp ital m ortality
fund ed by BCBSM, BCBSM d oes not have access to hospital- rate in 6488 consecu tive op erations. This stu d y set the stage
specific d ata. In ad d ition, only the lead ership of the collab- for m u lti-institu tional, regional collaboration for surgical
orative has access to hospital-specific d ata. Both BCBSM qu ality im p rovem ent.
and the p articip ating centers have m ad e a com m itm ent not
to seek the ou tcom es d ata from other hospitals. Initially, ■ American College of Surgeons-National Surgical
potential p articip ants w ere concerned that BCBSM m ight
Quality Improvement Program
try to u se the d ata for selective contracting w ithin the state.
This has not happened . In fact, w hen w e su rveyed the The m ost p rom inent nationally based qu ality collaborative
nu rses and su rgeons at a quarterly m eeting, 100% rep orted is the ACS-N SQIP. The ACS-N SQIP w as d eveloped by
that BCBSM w as a reliable p artner. Shukri Khu ri in response to a call from the Congress
Local p rofessional organizations, su ch as state chap ters regard ing fears of low quality care w ithin the Veterans
of the Am erican College of Surgeons (ACS), can p rovid e H ealth Ad m inistration. The N SQIP established m ethod s
the core lead ership of new collaboratives. Active m em bers for reliable d ata collection and risk-ad ju sted assessm ent of
of su ch societies tend to be senior su rgeons. The su rgeons center-sp ecific p erform ance. Presu m ably related to this
w ill likely have alread y d evelop ed a collegial relationship w ork, remarkable red u ctions in su rgical com plications
among them selves. It is critical that collegiality am ong the w ere noted w ithin Veterans Affairs (VA) Med ical Centers
su rgeon lead ership sets the tone for the entire collabora- (5,40,41). More recently, the N SQIP has p artnered w ith the
ACS and has been su ccessfully im plem ented in private sec- MS QC S S I ra te s for e le ctive ca s e s
tor hosp itals (31). Cu rrently, there are approxim ately 200 5.0
private sector hosp itals enrolled in the ACS-N SQIP. 4.5
The ACS-N SQIP p rovid es high qu ality com p arative Yo ur
4.0
d ata to hospitals to facilitate internal qu ality im provem ent Ho s pital
3.5
efforts. The early success of the ACS-N SQIP is largely
P re ce nt S S I
related to accep tance by su rgeons of the quality of the d ata 3.0
and analysis. As a tool for qu ality im provem ent, m any 2.5 Hig h-
qu estions su rrou nd ing its u tility. In ord er to m axim ize the 2.0 Pe rfo rming
Ho s pitals
benefits of the ACS-N SQIP, there need s to be a m ed iu m in 1.5
w hich d ata can be evalu ated and tu rned to qu ality 1.0
im provem ent. It had been assu m ed that this w ould occu r
0.5
at the hosp ital level, but m ay not be occu rring. This is
0.0
w here a regional collaborative m ay p rovid e im p ortant su p -
plem entation to ACS-N SQIP p articipation. FIGURE 8.4. As an example of data feedback received by participating hos-
pitals, this Pareto chart compares surgical site infection (SSI) rates for elec-
tive cases among MSQC hospitals. Red bars on left represent high outliers or
■ Michigan Surgical Quality Collaborative “poor performers.” With our quality improvement efforts, we focus on the
right side of the figure or “high performing hospitals.” We identify these hos-
Ou r exp erience in Michigan w ith a su ccessfu l qu ality col- pitals and they share best practices.
laborative has been w ith the MSQC. This is a group of 34
mostly com m unity hospitals w ithin Michigan that w as
established in 2005. Based on the w ork of others, w e recog-
nized an opportu nity for partnership w ith a large p rivate op erative insu lin p rotocol to share w ith the grou p . Another
payer w ithin the state. Sim ilarly, it becam e clear that the hospital talked abou t the im portance of intraoperative glu-
best w ay to overcom e strong institutional biases that m ay cose m onitoring. Discu ssions of com p lications centered on
stifle qu ality im p rovem ent w as to collaborate w ith other the high p erform ing hosp itals in an effort not to alienate
hospitals throu ghou t the state (3,6,20,22,32,42,43). The p oor p erform ing hosp itals. Continu ing w ith ou r them e of
resu lts show ed a significant red u ction in su rgical com p lica- SSI, w e then had a national exp ert in SSI review evid ence-
tion rates w ithin Michigan (Fig. 8.1). based p ractices and p articip ate in a qu estion and answ er
Each p articip ating hosp ital is enrolled in the ACS- session. Overall, su rgeon and nu rsing lead ers throughou t
N SQIP. The collaborative is based on the stru cture and d ata Michigan w ere able to hear granu lar qu ality im p rovem ent
of the ACS-N SQIP. In ad d ition, the MSQC also has its ow n ap p roaches by other institu tions w ithin the state and bal-
d ata coord inating center at the University of Michigan ance these efforts w ith the best available d ata on SSI. H igh
w h ich facilitates rap id an d focu sed an alyses th at are qu ality d ata ind icating p oor perform ance is very influ en-
germ an e to th e p articip an ts. H osp itals receive qu arterly tial w ith hosp ital ad m inistrations. These su rgeons and
rep orts com p aring their risk-ad ju sted ou tcom es to both nu rses, arm ed w ith this d ata and know led ge, are u niquely
national averages and to the other p articipating hospitals w ell su ited to lead qu ality im p rovem ent efforts w ithin
w ithin Michigan. The reports clearly ind icate an ind ivid u al hom e institutions.
center ’s p erform ance, as w ell as high and low p erform ing Within the MSQC, som e u niqu e initiatives have gar-
hosp itals (Fig. 8.4). Significant efforts are m ad e to m ake nered significant enthu siasm am ong p articip ants. We have
these rep orts easily u nd erstood by all su rgeons, nu rses, created a nu m ber of QI vid eos on You Tu be™. Som e
and qu ality im p rovem ent p rofessionals. In ad d ition, w e vid eos have exp erts w ithin the collaborative exp lain their
d iscu ss how to best com m u nicate these d ata w ith hosp ital su ccessfu l p rocesses of care. For exam p le, one institution
ad m inistration. w ith rem arkable ou tcom es follow ing colectom y sp ecifi-
A key asp ect of th e MSQC is its qu arterly m eetin gs. cally d etailed their p reop erative assessm ent, op erative
At th ese m eetin gs, h osp ital rep orts are d istribu ted to m anagem en t, an d p ostop erative care. In ad d ition , w e fre-
su rgeon s, n u rses, and other m em bers of hosp ital team . qu ently invite prom inent national experts to our qu arterly
Atten d an ce is a requ irem en t for p articip ation . In cen tive m eetings. We interview these ind ivid u als and p ost the
p aym ents to institu tions w ill be w ithheld from any insti- vid eo. Links to these vid eos are read ily available on the
tu tion th at d oes n ot actively p articip ate an d atten d th e MSQC w ebsite. We have encou raged su rgeons and clinical
m eetings. nu rse review ers to bring QI officers and ad m inistrators
Each m eeting has a them e related to a sp ecific QI initia- from their institu tions. These are the ind ivid u als that w ill
tive. For exam p le, in a recent m eeting w e noticed a 10-fold be actively p articip ating in the grassroots effort to im prove
variation in SSI rates am ong d iabetic p atients follow ing qu ality w ithin m em ber institu tions, and their involvem ent
elective su rgery. We alw ays m ake an effort to focus on high in the qu arterly m eetings is critical. Du ring recent quar-
perform ing hosp itals. We asked these hospitals w hy they terly m eetings, w e have u sed real-tim e au d ience responses
had su ch good resu lts. One hospital brou ght in their p eri- to better u nd erstand cu rrent p rocesses of care. We w ill
4% Unlike m any national initiatives, the collegial atm os-

p here w ithin the collaborative is critical to foster d etailed
* and honest d iscu ssions of ou tcom es, good or bad . BCBSM
has supported the collaborative approach to QI w ithin
their broad -based QI “p ay-for-p articip ation” p rogram s.
P re ce nt of pa tie nts
*
* There been significant red u ctions in the rate of com p lica-
tions follow ing m ajor su rgery. In ad d ition, there have been
2%
reductions in the rates of serious postoperative complica-
tions such as sepsis, pneumonia, and card iac arrest. (Fig. 8.5)
H opefu lly this trend tow ard QI w ill continu e.
*
*
■ SUMMARY
0% Surgical quality collaboratives offer significant opportu ni-
S e ps is P ne umonia Ve nt >48 S e ptic Ca rdia c
hours S hock a rre s t ties for QI and cost savings. There are several core com po-
nents to a su ccessfu l collaborative. In Michigan, largely
MS QC Time Pe rio d 1 MS QC Time Pe rio d 2 becau se of the su p p ort from BCBSM, w e have had signifi-
FIGURE 8.5. Changes in rates of major postoperative complications cant su ccess w ith the MSQC. In ord er to get a better u nd er-
between the first 2 years of the MSQC (MSQC Time Period 1) and the third year stand ing of the perceptions of participating su rgeons and
(MSQC Time Period 2). *p 0.05 nu rses, w e recently su rveyed MSQC nu rses and su rgeons.
(Fig. 8.6) The resu lts of this su rvey highlight critical com po-
choose 10 sp ecific questions regard ing processes of care nents of a qu ality collaborative. Im p ortantly, 100% of
and have attend ees resp ond in real tim e. Attend ees w ill be respond ents rep orted that there is a high d egree of colle-
able to com p are their hospital’s processes of care to those of giality w ithin the grou p . Sim ilarly, 100% of resp ond ents
other hosp itals w ithin Michigan. This can provid e signifi- reported that BCBSM is a reliable partner in the collabora-
cant insights, p articularly to hosp itals w ith poor ou tcom es tive. The im p ortance of financial su p p ort by BCBSM for
and in an anonym ou s, nonthreatening w ay. p articip ation is clear, w ith 77% of resp ond ents reporting
The focu s of the MSQC stand s in stark contrast to that it is necessary. Finally, only 2% of the respond ents
recently im p lem ented Center for Med icare and Med icaid reported that they felt reluctant to d iscu ss qu ality problem s
Services (CMS) p olicies for nonp aym ent for hosp ital w ithin the home institution.
acqu ired cond itions, otherw ise know n as “never events.” Obviou sly, the d evelop m ent of the qu ality collabora-
Clearly, certain clinical events, such as w rong p atient or tives m ust rely u pon the strengths of the p otential partici-
w rong sid e su rgery, should be consid ered “never events.” p ants. Most su ccessfu l collaboratives have been regional
Unfortu nately, su ch policies focusing on poor ou tcom es and have had a narrow clinical focu s. In ad d ition, quality
w ithin an institu tion m ay d etract from real QI by d riving collaboratives frequ ently have their genesis w ithin local
clinical p roblem s u nd erground . The focu s shou ld rem ain p rofessional societies su ch as state chap ters of the ACS.
on high p erform ers, rew ard ing their efforts and ou tcom es. H op efu lly, su rgical collaboratives w ill continue to expand
S urvey of MS QC s urge ons a nd nurs e s FIGURE 8.6. Results of a survey of MSQC nurses
and surgeons. The results of this survey highlight criti-
cal components for all the quality collaboratives.
Colle gia lity is high 100%
BCBS M is a re lia ble

100%
pa rtne r
Fina ncia l s upport

77%
ne ce s s a ry
Us e d for compe titive

16%
a dva nta ge
Re lucta nt to dis cus s

2%
proble ms
throu ghou t the United States. This offers the opportu nity 23. Bratzler DW, H u nt DR. The su rgical infection p revention and su rgical
care im provem ent projects: national initiatives to im prove ou tcom es
for su rgeons to lead efforts to im prove su rgical care. In for p atients having su rgery. Clin Infect Dis 2006;43(3):322–330.
ad d ition and m ost im portantly, it w ill lead to better care for 24. Cam p bell DA, Englesbe MJ, Ku bu s JJ, et al. Accelerating the p ace of
ou r p atients. su rgical qu ality im p rovem ent: the p ow er of hosp ital collaboration.
Arch Surg 2010;145(10):985–991.
25. Producer price index for the direct health and medical insurance carriers
■ REFERENCES industry. U. S. Departm ent of Labor, Bu reau of Labor Statistics; 2007.
Available at: w w w.bls.gov. Accessed Ju ne 19, 2009.
1. Birkm eyer JD, Siew ers AE, Finlayson EV, et al. H osp ital volu m e and 26. Englesbe MJ, Dim ick JB, Sonnend ay CJ, et al. The Michigan su rgical
su rgical m ortality in the United States. N Engl J Med 2002;346(15): qu ality collaborative: w ill a statew id e qu ality im p rovem ent initiative
1128–1137. pay for itself? Ann Surg 2007;246(6):1100–1103.
2. Birkm eyer JD, Stukel TA, Siew ers AE, et al. Su rgeon volu m e and op er- 27. Birkm eyer JD, Shahian DM, Dim ick JB, et al. Blu ep rint for a new Am er-
ative m ortality in the United States. N Engl J Med 2003;349(22): ican College of Su rgeons: N ational Su rgical Qu ality Im p rovem ent Pro-
2117–2127. gram . J Am Coll Surg 2008;207(5):777–782.
3. Flu m DR, Fisher N , Thom p son J, et al. Washington State’s ap p roach to 28. Cu schieri J, Florence M, Flu m DR, et al. N egative ap p end ectom y and
variability in su rgical processes/ Ou tcom es: Surgical Clinical Ou tcom es im aging accu racy in the Washington State Su rgical Care and Outcom es
Assessm ent Program (SCOAP). Surgery 2005;138(5):821–828. Assessm ent Program . Ann Surg 2008;248(4):557–563.
4. H annan EL, Kilbu rn H Jr, O’Donnell JF, et al. Ad u lt op en heart su rgery 29. Cohn JA, Englesbe MJ, Ad s YM, et al. Financial im p lications of p an-
in N ew York State. An analysis of risk factors and hosp ital m ortality creas transplant com plications: a bu siness case for quality im prove-
rates. JAMA 1990;264(21):2768–2774. m ent. Am J Transplant 2007;7(6):1656–1660.
5. Khuri SF, Daley J, H end erson W, et al. The N ational Veterans Ad m inis- 30. Moscu cci M, Muller DW, Watts CM, et al. Red u cing costs and im p rov-
tration Su rgical Risk Stu d y: risk ad ju stm ent for the com p arative assessing ou tcom es of p ercu taneous coronary interventions. Am J Manag Care
m ent of the qu ality of su rgical care. J Am Coll Surg 1995;180(5):519–531. 2003;9(5):365–372.
6. O’Connor GT, Plu m e SK, Olm stead EM, et al. A regional intervention 31. Khuri SF, Henderson WG, Daley J, et al. Successful implementation of the
to im p rove the hosp ital m ortality associated w ith coronary artery Department of Veterans Affairs’ National Surgical Quality Improvement
byp ass graft su rgery. The N orthern N ew England Card iovascu lar Program in the p rivate sector: the p atient safety in su rgery stu d y. Ann
Disease Stud y Group . JAMA 1996;275(11):841–846. Surg 2008;248(2):329–336.
7. N eum ayer L, Mastin M, Vand erhoof L, et al. Using the Veterans 32. Moscu cci M, Share D, Kline-Rogers E, et al. The Blu e Cross Blu e Shield
Ad m inistration N ational Surgical Qu ality Im provem ent Program to of Michigan Card iovascu lar Consortiu m (BMC2) collaborative qu ality
im p rove p atient outcom es. J Surg Res 2000;88(1):58–61. im provem ent initiative in p ercu taneou s coronary interventions. J
8. Polk H C Jr, Birkm eyer J, H u nt DR, et al. Qu ality and safety in su rgical Interv Cardiol 2002;15(5):381–386.
care. Ann Surg 2006;243(4):439–448. 33. Khu ri SF, Daley J, H end erson W, et al. The Dep artm ent of Veterans
9. Englesbe MJ, Dim ick JB, Fan Z, et al. Case m ix, qu ality and high-cost Affairs’ N SQIP: the first national, valid ated , ou tcom e-based , risk-
kid ney transplant patients. Am J Transplant 2009;9(5):1108–1114. ad ju sted , and peer-controlled p rogram for the m easu rem ent and
10. Englesbe MJ, Dim ick J, Mathu r A, et al. Who p ays for biliary com p lica- enhancem ent of the quality of su rgical care. N ational VA Su rgical Qu al-
tions follow ing liver transp lant? A business case for qu ality im prove- ity Im p rovem ent Program . Ann Surg 1998;228(4):491–507.
m ent. Am J Transplant 2006;6(12):2978–2982. 34. H annan EL, Ku m ar D, Racz M, et al. N ew York State’s Card iac Su rgery
11. Dim ick JB, Weeks WB, Karia RJ, et al. Who p ays for p oor su rgical qual- Rep orting System : fou r years later. Ann Thorac Surg 1994;58(6):
ity? Bu ild ing a bu siness case for qu ality im p rovem ent. J Am Coll Surg 1852–1857.
2006;202(6):933–937. 35. H annan EL. Rep ort card s: are they p assing or failing? One N ew
12. Dim ick JB, Chen SL, Taheri PA, et al. H osp ital costs associated w ith su r- Yorker says they’re p assing. Clin Perform Qual Health Care 1996;4(4):
gical com p lications: a rep ort from the p rivate-sector N ational Su rgical 218–219.
Qu ality Im p rovem ent Program . J Am Coll Surg 2004;199(4):531–537. 36. Dim ick JB, Welch H G, Birkm eyer JD. Su rgical m ortality as an ind icator
13. Galvin RS, Delbanco S, Milstein A, et al. H as the leap frog grou p had an of hosp ital qu ality: the problem w ith sm all sam p le size. JAMA 2004;
im pact on the health care m arket? Health Aff (Millwood) 2005;24(1): 292(7):847–851.
228–233. 37. H all BL, Cam p bell DA Jr, Ph illip s LR, et al. Evalu atin g in d ivid u al
14. Milstein A, Galvin RS, Delbanco SF, et al. Im p roving the safety of su rgeon s based on total hosp ital costs: evid ence for variation in
health care: the leap frog initiative. Eff Clin Pract 2000;3(6):313–316. both total costs an d volatility of costs. J Am Coll Surg 2006;202(4):
15. Rosenthal MB, Dud ley RA. Pay-for-p erform ance: w ill the latest p ay- 565–576.
m ent trend im prove care? JAMA 2007;297(7):740–744. 38. H all BL, H irbe M, Waterm an B, et al. Com p arison of m ortality risk
16. Rosenthal MB. Beyond p ay for p erform ance–em erging m od els of ad ju stm en t u sin g a clin ical d ata algorith m (Am erican College of
p rovid er-p aym ent reform . N Engl J Med 2008;359(12):1197–1200. Su rgeons N ation al Su rgical Qu ality Im p rovem ent Program ) and an
17. Fu ng-Kee-Fu ng M, Gou banova E, Sequ eira K, et al. Develop m ent of ad m inistrative d ata algorithm (Solu cient) at the case level w ithin a
com m unities of practice to facilitate quality im provem ent initiatives in single institu tion. J Am Coll Surg 2007;205(6):767–777.
su rgical oncology. Qual Manag Health Care 2008;17(2):174–185. 39. O’Connor GT, Qu inton H B, Traven N D, et al. Geograp hic variation in
18. Fu ng-Kee-Fu ng M, Watters J, Crossley C, et al. Regional collaborations the treatm ent of acu te m yocard ial infarction: the Coop erative Card io-
as a tool for qu ality im p rovem ents in su rgery: a system atic review of vascu lar Project. JAMA 1999;281(7):627–633.
the literature. Ann Surg 2009;249(4):565–572. 40. Daley J, Khu ri SF, H end erson W, et al. Risk ad ju stm ent of the p ostop er-
19. Pronovost P, N eed ham D, Berenholtz S, et al. An intervention to ative m orbid ity rate for the com parative assessm ent of the qu ality of
d ecrease catheter-related blood stream infections in the ICU. N Engl J su rgical care: resu lts of the N ational Veterans Affairs Su rgical Risk
Med 2006;355(26):2725–2732. Stud y. J Am Coll Surg 1997;185(4):328–340.
20. Moscu cci M, Rogers EK, Montoye C, et al. Association of a continu ou s 41. Brow n RS Jr, Ascher N L, Lake JR, et al. The im p act of su rgical com p li-
qu ality im p rovem ent initiative w ith p ractice and ou tcom e variations of cations after liver transp lantation on resou rce u tilization. Arch Surg
contem p orary p ercu taneou s coronary interventions. Circulation 2006; 1997;132(10):1098–1103.
113(6):814–822. 42. Shroyer AL, Coom bs LP, Peterson ED, et al. The Society of Thoracic
21. Khu ri SF, H end erson WG. The p atient safety in su rgery stu d y. J Am Coll Su rgeons: 30-d ay operative m ortality and m orbid ity risk m od els. Ann
Surg 2007;204(6):1087–1088. Thorac Surg 2003;75(6):1856–1864; d iscu ssion 1864–1855.
22. Chassin MR. Achieving and su staining im p roved qu ality: lessons from 43. Bratzler DW. The Su rgical Infection Prevention and Su rgical Care
N ew York State and card iac su rgery. Health Aff (Millwood) 2002;21(4): Im p rovem ent Projects: prom ises and p itfalls. Am Surg 2006;72(11):
40–51. 1010–1016; d iscussion 1021–1030, 1133–1048.
CHAPTER
Patient Safety
Darrell A. Campbell
■ IMPORTANT DEFINITIONS: SAFETY every m ajor com m ercial aircraft flight, d eaths from m ed -
VERSUS QUALITY ical error w ou ld be equ ivalent of 63 sep arate m id -air colli-
sions p er year in the airline ind u stry or five p er m onth.
The term s qu ality and safety have im p ortant bearings on Im agine the p u blic ou tcry this w ou ld p rod u ce, the law s
any d iscu ssion of patient care. These are related su bjects that w ou ld be qu ickly p assed , and the boon to travel on
bu t have d ifferent m eanings, and these d ifferences shou ld Am trak that w ou ld resu lt. Bu t this is not w hat has hap-
be u nd erscored before any d ialogu e abou t patient safety p ened in m ed icine. The governm ent resp onse has been
begins. Safety m eans “freed om from harm ”; in the context w eak at best, and the m ed ical com m u nity has been slow to
of p atient care, “safety” m eans freed om from harm associ- acknow led ge and even slow er to resp ond to the safety
ated w ith any m ed ical action or treatm ent. Qu ality is a im perative.
more global term referring to a “d egree of excellence.” It is
theoretically p ossible for a hospital to be safe, bu t for qu al-
ity to be average or poor. It is not possible, how ever, for a ■ CULTURE
hosp ital to be of high quality and u nsafe. In this chap ter w e
focu s p rim arily on the subject of p atient safety, bu t ad m it Cu ltu re is d efined as “how w e d o things arou nd here.”
that som e asp ects of the su bject d rift into the area of qu ality That is, there is a certain level of accep tance for w hat goes
as w ell. on in a given hosp ital. That accep tance is based on tw o pre-
cep ts that in the p ast have not been challenged . One pre-
cep t is that m ed ical errors exist becau se “hu mans w ill
■ THE PROBLEM alw ays m ake m istakes.” While su p erficially true, this state-
By now all are familiar w ith the report issued by the Institute m ent fails to acknow led ge that m od ern hu m an factors
of Med icine (IOM) in 2000 entitled , “To Err is H uman” (1). engineering strategies can m ilitate against com m only
The report w as an exhaustive review of the status of safety encou ntered errors. A concrete exam p le of how hu m an fac-
in ou r nation’s hosp itals. The bottom line—w hich served tors engineering can be brou ght into p lay involves som e-
as a “burning platform” for the patient safety movement— thing as sim p le as a connector for m ed ical tu bing. If the
w as the astonishing calcu lation that betw een 44,000 and connector is d esigned su ch that it is not p ossible to connect
98,000 Am erican s d ied an nu ally in h osp ital as the resu lt an O 2 line to a CO 2 valve, a p otentially catastrop hic m is-
of p reventable m ed ical error. The rep ort p rod u ced a flu rry take becom es im p ossible. More globally, w ork hour restric-
of ou trage from consu m er grou p s, and d enials and refu tations for m ed ical trainees, w hich red u ce fatigu e, cou ld be
tions from m ed ical grou p s, bu t w hen the d u st settled expected to resu lt in few er errors by exhau sted and stressed
w hat w as left w as the recognition, by all grou p s, that d octors. To d ate, hu man factors engineering has not been
som ething w as seriou sly w rong in ou r m ed ical care d eliv- brou ght into the d elivery of m ed ical care effectively. While
ery system . hu m ans w ill alw ays be cap able of m aking m istakes, the
Com parisons are often m ad e betw een the safety of air- nu m ber of m istakes w ill be red u ced if d esign is targeted to
line travel and m ed ical care. One airline d isaster every tw o w hat w e know abou t hu m an fallibilities.
or three years p rod u ces calls for new regu lation, better air- The second p recep t accou nting for com p lacency is the
ports, m ore frequ ent m echanical checks, and earlier retire- notion that a m ed ical error is the resu lt of p oor ind ivid u al
ment for p ilots. But consid er m ed ical care. If even the low er p erform ance rather than an imp erfect system of care. If an
nu m ber of preventable d eaths extrapolated by the IOM ind ivid u al m ad e the error, in isolation, the only corrective
rep ort (44,000 annu ally) w ere seen as accu rate, and one step w ou ld be to d ism iss the hap less caregiver or im m erse
accep ted that an average of 350 passengers w ere on board him or her in intensive rem ed ial ed u cation. The problem
w ith this ap p roach is that it d oes not ap p ly to the next hap -
less caregiver faced w ith the sam e situ ation. And so, since
Darrell A. Campbell: University of Michigan H ealth Sys- there is a high tu rnover in m ost m ed ical environm ents,
tems, Ann Arbor, MI 48109. m istakes continu e to hap p en, caregivers continu e to be
53
d ism issed , and nothing really changes. This sequence has ou tp atient environm ent in fam ily p ractice, safety problem s
been ingrained in the m ed ical cu ltu re, and it is w hy the typ ically involve p oor hand offs, failu res of team w ork,
med ical com m u nity has been slow to respond to the safety excess w orkload , and fatigu e (4).
crisis. Bu t w hat abou t the concep t of ind ivid u al resp onsibil-
ity? One can not show u p for w ork w ith a careless attitud e,
engage in irresp onsible actions, and exp ect to be held
■ SWISS CHEESE AND MEDICAL ERRORS
im m une from poor p erform ance becau se of the em p hasis
A p op u lar p arad igm in the m ed ical safety area is the on system s. This is a d elicate balance for any healthcare
“Sw iss cheese” m od el, introd uced by James Reason (2). system . The u nd erlying p rincip le here is that m ost em ploy-
(Fig. 9.1) This m od el is a visual representation of the m u lti- ees of a hosp ital w ake u p each m orning w anting to d o a
ple system layers that cou ld prevent a m ed ical error from good job and to avoid m istakes, and hence (w ith excep-
occurring. A beam of light representing a latent error tions) the general p hilosop hy shou ld be that a m ajor
passes throu gh a hole in the cheese representing a system im provem ent in safety w ill be at the level of system engi-
of vu lnerability. The latent error passing throu gh the sys- neering rather than ind ivid u al fallibility. When the onu s of
tem via vu lnerability w ill resu lt in a m ed ical error. If ind ivid ual fallibility is lessened (not entirely), there em erges
enough system s are set up w ith vulnerabilities, bu t in d if- a new sense of system responsibility, w ith increased w ill-
ferent locations, it becom es progressively hard er for the ingness to id entify system errors and to p articipate in
latent error to becom e manifest clinically. The point here is safety enhancem ent as a grou p . This collaborative p artici-
that, w hile w e recognize that hum ans have vulnerabilities p ation d oes not occu r w hen one is w orried abou t pu nitive
and system s of care have vu lnerabilities, the prevention of consequ ences for rep orting and the p ossibility of job loss.
error lies at the d oor of hospital lead ership. Positive resu lts
com e from the establishm ent of effectively red und ant sys-
tem s of error p revention. This concept is a m ajor parad igm
■ LEADERSHIP AND POLICY
shift in the p atient safety m ovem ent. H ow to change a cu ltu re? This is not d one easily. There are
Even thou gh the system shou ld be constru cted to tw o cru cial elem ents w hich, if effective, can change the cu l-
backu p hu m an fallibilities, it is instru ctive to recognize tu re d irection p ositively. The first elem ent is set by the
the fallibilities. This su bject is hard to qu antify, bu t a good examp le of hosp ital lead ership . When the rank and file sees
list, d evelop ed in a fam ily p ractice environm ent, read s as that the hosp ital CEO p laces p atient safety at the top of the
follow s: hu rry, d istraction, lack of know led ge, p rem atu re list and backs this p riority u p w ith fu nd ing, a nu m ber of
closure of the d iagnostic process, and inad equ ate aggres- good things hap p en. When the CEO em p hasizes a change
siveness in p atient m anagem ent (3). The first three issu es in hosp ital p olicy w ith an em p hasis on safety, the change is
are probably obviou s, but prem ature closure of the d iag- reinforced . We introd u ced tw o p olicies that serve as exam -
nostic p rocess is a p roblem need ing em phasis. H u m ans p les of this p oint. The first, the “fu ll d isclosu re” p olicy, stip-
often fall into this trap . We see issues as black and w hite, in u lated that employees w ere obligated (not ju st encouraged )
an attem p t to m ake sense ou t of com plex circu m stances. to d isclose fully to p atients im portant errors m ad e in ren-
H u rry, d istraction, and lack of know led ge contribute. Rele- d ering their care. Rem arkably, this p olicy resu lted in few er
vant p ieces of Sw iss cheese, w hich could counteract this m alp ractice claim s against the system , bu t m ore im por-
tend ency, includ e electronic d iagnosis and d ecision-making tantly, it und erscored for employees the institutional em pha-
aid s, an institu tional policy fostering physician interac- sis on op enness and honesty (5). The second p olicy change
tions, team w ork, and second opinions, and setting and im p lemented w as the “sp eak u p w ith safety concerns” p ol-
ad hering to reasonable w orkload stand ard s. icy, w hich stip u lated that no caregiver cou ld be pu nished
Dep end ing on the environm ent, other fallibilities are for voicing a concern involving p atient safety, regard less
exposed . In the acu te hospital setting, as opp osed to the of feelings hu rt or hierarchy violated . Again, this w ritten
FIGURE 9.1. Systems failures (Reproduced with per- S ys te ms Failure s

mission from Mulholland, MW, et al., eds. Greenfield’s
Surgery: Scientific Principles and Practice, Fifth Edition.
Philadelphia: Lippincott Williams & Wilkins, 2010; Figure
16.1).
Error
S e rio us e rro rs are fre que ntly the re s ult o f

s mall, multiple s ys te m failure s
Chapter 9 • Patient Safety 55
UMHS Ris k Manag e me nt Eve nts Re po rte d FIGURE 9.2. Overview of the reporting
18,000 system (Reproduced with permission from
Mulholland, MW, et al., eds. Greenfield’s
? Surgery: Scientific Principles and Prac-
16,000 ? 15,680 tice, Fifth Edition. Philadelphia: Lippincott
? 14,108 Williams & Wilkins, 2010; Figure 16.2).
14,000
Numbe r of Eve nts Re porte d
12,000
11,005
10,000
8,000
6,706
6,000
4,668
3,891
4,000 3,511 3,455
3,189
1,880
2,000 1,381
788
417 128
66 76
44
0
1999 2000 2001 2002 2003 2004 2005 2006 2007
Ca le nda r Ye a r
Vo lu n ta ry re p o rtin g include s “ne a r-mis s e s ” a s we ll a s eve nts tha t re s ult in pa tie nt ha rm

• Incre a s e d re porting with low ra te of pa rma ne nt ha rm eve nts is de s ire d
• Goa l—e nha nce pa tie nt s a fe ty a nd improve qua lity of ca re ; eve nts mutua lly exclus ive
policy clearly articu lated a health system goal—that the qu estion “are w e im p roving the safety cu ltu re” and , if
patient safety tru m ped all other consid erations. not, w hat are the areas that need to be ad d ressed institu -
One m anifestation of an im p roved safety cu ltu re is an tionally. In ou r last su rvey, a clear sore p oint at ou r institu -
increased error reporting rate. Clearly the error rep orting tion w as d ifficu lty w ith “hand offs” or the transfer of
rate w ill not go u p if there exists w id esp read fear of retri- inform ation betw een caregivers and team s. We then d evel-
bu tion for rep orting. What is d esired is an increased rate of op ed a task force focu sed on fixing the p roblem , over both
error rep orting, bu t a d ecreasing rate of events resu lting in short and long term . The long-term solu tion is an electronic
tem p orary or p erm anent harm . This pattern su ggests that one, bu t w e also need ed a short term solu tion. A paper-
caregivers are vigilant, care abou t safety, and are rep orting based hand off tool d esigned to ad d ress the hand off issu e
on “near m isses.” The d ata from “near m isses” rep resent a in the short term w as qu ickly d evelop ed . This effort w as a
treasu re chest of inform ation that can be u sed to p revent d irect resu lt of inform ation gained from the safety cu ltu re
actu al m istakes. We have seen increased rep orting in asso- su rvey.
ciation w ith the pu rchase of a new electronic reporting for- A second w ay w e u se the safety cultu re survey d ata is to
mat. Whether a change in cu lture or a change in rep orting id entify sp ecific hosp ital u nits that are stru ggling w ith a
form at is responsible for the increased level of reports is d isp irited or com p lacent attitu d e tow ard the safety effort.
hard to say, bu t w e believe that it is a com bination of both Su ch p roblem s often resu lt from p oor nu rse lead ership ,
(Fig. 9.2). d isru p tive p hysicians, or a lack of p erceived resou rces.
Arm ed w ith inform ation about the safety cultu re (or lack of
it), the institu tion can im p lem ent a focu sed strategy cu s-
■ ASSESSING THE CULTURE tomized to the p roblem . Figu re 9.3 show s results from ou r
If one p laces p riority on “im proving” a safety cu ltu re, it is su rvey arranged by an ind ivid u al nu rsing u nit, d em on-
necessary for the “cu ltu re” to be m easu red . Valid ated cu l- strating certain u nits in need of help w ith error rep orting,
tu re su rveys exist, w hich, if applied period ically in a hosp i- and conversely, u nits w here the cu ltu re is good and institu-
tal environm ent, give im portant insight into the su ccess of tional resou rces are not need ed . A third sou rce of inform a-
the safety cu ltu re initiatives. We u se the Agency for H ealth- tion d erived from the su rvey com es from narrative
care Research and Qu ality (AH RQ) safety cultu re instru- com m ents entered by ind ivid u al caregivers. This is a very
ment p rim arily, and survey all caregivers at app roxim ately rich sou rce of inform ation and , since it is anonym ou s,
tw o-year intervals. We u se the resulting inform ation in often d raw s a fine line u nd er issu es that are hard to talk
three w ays. First, w e use the aggregate response to answ er abou t in any other foru m . Issu es of su sp ected physician
% o f re s po nde nts in e ac h nurs ing unit re s po nding with

“Dis ag re e ” o r “S tro ng ly Dis ag re e ” whe n as ke d the s e que s tio ns .
100%
90%
80%
80%
70% 68% 68% 68%

65%
62% 62% 63%
60%
60%
56% 57%
53%
50% 49%
48%
45%
41%
40% 39%
36%
33%
29% 30%
30%
25%
19%
20% 17% 17%
10%
0%
No npunitive Re s po ns e to Erro r
• S ta ff fe e l like the ir mis ta ke s a re he ld a ga ins t the m (reve rs e worde d).
• Whe n a n eve nt ge ts re porte d, it fe e ls like the pe rs on is be ing writte n up, not the proble m (reve rs e worde d).
• S ta ff worry tha t mis ta ke s they ma ke a re ke pt in thie r pe rs onne l file s (reve rs e worde d).
FIGURE 9.3. Nonpunitive response to error (Reproduced with permission from Mulholland, MW, et al., eds. Greenfield’s Surgery:
Scientific Principles and Practice, Fifth Edition. Philadelphia: Lippincott Williams & Wilkins, 2010; Figure 16.3).
im pairm ent, abu sive behavior, or lack of lead ership skills d iscussion ensues w ith the unit caregivers, includ ing nu rses,
are som etim es id entified . aid es, clerks, and transp orters. The cu ltu re effects of this
Tw o im p ortant qu estions regard ing safety cu ltu re and end eavor are p rofou nd . When caregivers believe that lead -
our efforts to im p rove it rem ain. First, using the AH RQ ership is w illing to listen, takes safety very seriou sly, and
tool, have w e seen an aggregate im provem ent over the p ast w ill p u t resou rces behind the articu lated concerns, an
tw o su rvey intervals? Many safety initiatives have been overall feeling of confid ence and su p p ort of the safety
institu ted over this p eriod of tim e, and yet the aggregate effort follow s. Figu re 9.4 d em onstrates that caregivers hav-
cu ltu re d ata has not show n m uch change. We interpret this ing participated in patient safety round s view ed the patient
inform ation to m ean that mu ch m ore w ork need s to be safety environm ent m u ch m ore p ositively than those w ho
d one and that changing a cultu re is a hard thing to d o, akin had not.
to changing d irection of an aircraft carrier. Also, over the Bu t is a p ositive safety cu ltu re actu ally associated w ith
period of tim e w e have been stu d ying ou r cultu re, w e have im p roved safety? The assu m p tion is yes, bu t d ata w ere
observed that ou r institu tional activity has gone u p d ra- hard to com e by u ntil recently. In Michigan, a m u ltihosp ital
matically, the com p lexity of our patients has increased , and collaborative w as initiated (The Keystone Project), the
nu rsing tu rnover has been high. Und er these circu m - object of w hich w as to imp lem ent evid ence-based p ractices
stances no change in the safety cu ltu re d ata m ight be know n to d ecrease the incid ence of blood stream infections
view ed m ore op tim istically. (BSI) (6). One hu nd red seven hosp itals w ere involved , and
A second qu estion is “are there ind ivid u al strategies w e caregivers resp ond ed to the Safety Attitu d es Qu estionnaire
have used that influ ence the safety culture positively?” If (SAQ), similar to the AH RQ tool d escribed p reviously.
so, w e cou ld u se these strategies m ore broad ly. The answ er Resu lts (in cid en ce of BSI) w ere correlated w ith an sw ers
to this qu estion is yes. Patient safety round s have been an to the SAQ. The resu lts are seen in Figu re 9.5. There w as
im portant strategy that has imp roved the safety cultu re. an im p ortan t association noted betw een the best resu lts
Over the cou rse of the past several years, w e have m ad e (% red u ction in BSI) and the m ost p ositive answ ers to SAQ
safety rou nd s on over 125 occasions, at tw o w eek intervals. qu estions. This is only an association, (and su bject to the
Safety rou nd s are carried ou t by lead ership (Chief of u su al caveats abou t associations vs. cau se and effect) bu t
Staff, Chief of N u rsing, CEO, etc.) and a pointed 45-m inu te important nonetheless. These results support the underlying
100%
Table 9 .1 Evid en ce-ba sed in t er ven t ion s for sa fe
90% Re s ponde nts who pa rticipa te d in rounds p a t ien t ca r e
80% 77% Re s ponde nts who did not pa rticipa te in rounds
70% 67% • Appropriate use of prophylaxis to prevent venous thromboembolism.
60% 58% • Use of perioperative beta-blockers in appropriate patients to prevent
50%
50% perioperative morbidity and mortality.
40% • Use of maximum sterile barriers while placing central intravenous
40% 35% catheters to prevent infections.
30%
• Asking that patients recall and restate what they have been told
20% during the informed consent process.
10% • Continuous aspiration of subglottic secretions to prevent ventilator-
0% associated pneumonia.
Orga niza tiona l Fe e dba ck a nd Nonpunitive • Use of pressure relieving bedding materials to prevent pressure ulcers.
Le a rning/Qua lity Communica tion Re s pons e
Improve me nt About Error to Error • Use of real-time ultrasound guidance during central line insertion to
prevent complications.
FIGURE 9.4. Comparison of 2007 AHRQ data participants vs. nonpartici-
• Patient self-management for warfarin to achieve appropriate outpa-
pants in patient safety rounds (Reproduced with permission from Mulholland,
MW, et al., eds. Greenfield’s Surgery: Scientific Principles and Practice, Fifth tient anticoagulation and prevent complications.
Edition. Philadelphia: Lippincott Williams & Wilkins, 2010; Figure 16.4). • Appropriate provision of nutrition, with a particular emphasis on early
enteral nutrition in critically ill and surgical patients.
• Use of antibiotic impregnated central venous catheters to prevent
hyp othesis that w hen lead ership p rioritizes safety and catheter-related infections.
im p lem ents actions to su pport safety, caregivers reflect this
in their answ ers to the SAQ, and this is associated w ith
im proved patient safety.
it is very clear that patients alread y on su ch m ed ications
m u st be given these p ostop eratively. H ow ever, an initial
■ THE EVIDENCE BASE FOR PATIENT SAFETY interest in -blocker ad m inistration for p atients never hav-
As im portant as it is to lay a strong fou nd ation in safety cu l- ing received them p reviou sly d eclined rapid ly as the result
ture, the energy and enthusiasm of caregivers to provid e of the POISE trial (8). This w as an international rand om -
safe patient care must be rooted in activities that have been ized controlled trial focu sing on this sp ecific issu e, and
fou nd to be effective. Unfortunately there d oes not exist, at the resu lt, after analyzing m any thou sand s of p atients,
this point, a large base of evid ence in patient safety, largely w as that giving -blockers p eriop eratively to naïve
because the field is relatively young. Recently, the World p atients cau sed m ore harm than good . Sp ecifically, treated
H ealth Organization (WH O) convened a grou p to carefully p atients d evelop ed m ore trou blesom e brad ycard ia and
analyze existing stud ies and highlight effective strategies hyp otension than controls, and this resu lted in a higher
w ith an evid ence base (7). These are listed in Table 9.1. Com- incid ence of stroke, obviating the p otential benefit of the
ments about specific evid ence-based actions follow. d ru g in p reventing m yocard ial ischem ia.
With regard to the ad m inistration of p eriop erative Using m axim u m sterile barriers for central venous pres-
-blockers to p revent p ostop erative m yocard ial ischem ia, su re (CVP) catheter insertion, in ord er to p revent BSI m ay
100
FIGURE 9.5.
% of respondents within an ICU reporting good teamwork
Teamwork climate across Michigan ICUs (Repro-

duced with permission from Mulholland, MW, et al., eds. Green-
field’s Surgery: Scientific Principles and Practice, Fifth Edition.
Philadelphia: Lippincott Williams & Wilkins, 2010; Figure 16.5).
80
The s tro ng e s t pre dic to r o f clinic al exc e lle nc e :
c are g ive rs fe e l c o mfo rtable s pe aking up if they
pe rc e ive a pro ble m with patie nt c are
60
40
20
> 5 months with zero CA – BSIs
No BSI 21% No BSI 31% No BSI 44%

0
FIGURE 9.6. Venilator-associated pneumonia—UH ICUs 10.00
Rate per 1,000 Ventilator Days

(Reproduced with permission from Mulholland, MW, et al.,
eds. Greenfield’s Surgery: Scientific Principles and Practice, 8.00
Fifth Edition. Philadelphia: Lippincott Williams & Wilkins,
2010; Figure 16.6).
6.00
4.00
2.00
0.00
Ja
M 6
Ju 6
Se
Ja 6
M 7
Ju 7
Se
N 7
Ja 7
M 8
ov
ov
ar
ay
ar
ay
ar
ay
n-
l-0
n-
l-0
n-
p-
p-
-0
-0
-0
-0
-0
-0
-0
-0
06
07
08
06
0
6
8
Month/Year
seem obviou s, and the im plem entation of this protocol has best and m ost exp erienced m ind s together to synthesize
resulted , in m any stu d ies, in a d ram atic fall in the incid ence w hat all w ou ld agree to be best p ractices. Trials m ay com e
of this com p lication. This strategy is com plem ented by the later to support or refu te consensus.
use of antibiotic im pregnated CVP lines and the u se of A very influential grou p that d evelops consensu s
chlorhexid ine in the d aily m aintenance of the insertion site. gu id elines is the N ational Qu ality Foru m (N QF), an organ-
The u se of u ltrasou nd to help gu id e CVP line insertion is ization of a w id e variety of exp erts, consu m ers, govern-
clearly effective. m ent officials, and corp orate d irectors. The N QF several
Prevention of the feared com plication of ventilator- years ago p u blished its list of “30 Safe Practices” recom -
associated p neu m onia is a very im p ortant consid eration, m end ed for im p lementation. Becau se this chap ter is ori-
since this d evelop m ent has a high fatality rate and is very ented tow ard s su rgery, Table 9.3 lists a selection of the 30
expensive to treat. There is som e evid ence that the continu - safe p ractices germ ane to the inp atient setting.
ous asp iration of su bglottic secretions is im portant. Ou r
institution has been successfu l in d ecreasing the ventilator-
acqu ired p neu m onia rate d ram atically (Fig. 9.6), bu t has
■ CONSENSUS AND ACCREDITATION
used a m u ltip ronged strategy d escribed in Table 9.2. The N QF w orks closely w ith the Joint Comm ission (JCO).
When the N QF has reached consensu s on a sp ecific safety
p ractice, this is often translated into a JCO requ irem ent for
■ DEVELOPING CONSENSUS hosp ital accred itation, in this setting recognized as JCO
Given the p au city of real evid ence to achieve w hat w e “Patient Safety Goals.” These goals are more sp ecific than
think of as safe p atient care and becau se there is an u rgent consensu s gu id elines, and have m ore “bite” to them , in
need to act, another strategy has been d evised : to d evelop that all hosp itals need to fu lfill these requ irem ents in ord er
consensu s gu id elines. Althou gh su ch gu id elines are not to be accred ited . For examp le, Goal 7 “Red u ce the risk of
based on rand om ized trials, there is valu e in getting the health care associated infections” stip u lates, am ong other
Table 9 .2 Un iver sit y of M ich iga n p r ot ocol for

p r even t ion of ven t ila t or a cq u ir ed
p n eu m on ia (VAP) Table 9 . 3 N a t ion a l q u a lit y for u m sa fe p ra ct ices
• Hand washing/hand sanitizing • Create a culture of safety
• Chlorhexidine oral rinse prior to intubation, then q12 h on 0900–2100 • Explicit informed consent
schedule • ICU patients managed by critical care certified providers
• Oral care with swabs q2–3h • Implement computerized physician order entry
• Head of bed elevated 30–45 degrees on all patients at all times, • Implement protocol for wrong side/site prevention
unless medically contraindicated • Evaluate for venous thromboembolism/implement prophylactic
• Extubate early—as soon as safely possible protocols
• Turn off tube feedings when placing patients flat for turning or for • Develop facility-wide anticoagulation services
procedures, unless small bore feeding tube post pyloric • Adhere to effective measures for preventing blood stream infection
• Endotracheal tube tape changed every 48 hours • Implement appropriate methods (antibiotic administration) for the
• Minimal use of saline lavage prevention of surgical site infection
• Change ventilator tubing only when soiled • Evaluate each patient at admission for the risk of malnutrition
• Staff education and updates on VAP • Develop effective hand-sanitizing policies
things, that hosp itals have specific strategies in p lace to geons d o not object to this policy. But great concerns have
prevent su rgical site infection (SSI), that they provid e regu - been raised abou t other cond itions on the “never event” list,
lar feed back abou t SSI rates to caregivers, w ith follow -u p such as venous thromboembolism (VTE) or patient falls.
for 30 d ays, that they d iscontinue the u se of shaving as a The controversy arises because in these cases there d oes not
method of p reop hair rem oval, etc. Goal 8, “Red u ce the risk exist an evid ence base that w ould allow a hospital to elim i-
of p atient harm resu lting from falls” stip u lates that each nate these events entirely. Perfectly ap prop riate VTE pro-
hospital imp lem ents a specific Falls Red u ction Program. phylaxis, for example, only red u ces the incid ence of postop
VTE by 50%. This situation seems unfair, and the list of
“never event” cond itions is progressively grow ing longer.
■ CONSENSUS, ACCREDITATION,
Whether or not this strategy w ill really improve qu ality and
AND PAYMENT make patients safer remains to be seen.
The Center for Med icare and Med icaid Services (CMS) has
a nu m ber of gu id elines for im plementation of safety p rac- ■ PATIENT SAFETY INDICATORS
tices as they p ay a large fraction of the nation’s health care
bill. As it regard s safety in su rgery and in hosp ital care, AH RQ is another national grou p , w hich is fu nd ed by the
CMS has em barked on tw o im portant strategies. The first is N ational Institu te of H ealth. Several years ago AH RQ
the Su rgical Care Im p rovem ent Project (SCIP) w hose stated d evelop ed 21 p atient safety ind icators (PSI), w hich are
goal is to red uce the incid ence of selected su rgical com pli- thou ght to reflect an institu tion’s safety. These ind icators
cations 25% by the year 2010. To d o this CMS p rod u ced are cap tu red from a hosp ital’s cod ing system , u sing Inter-
several sp ecific p rocess m easu res that are requ ired to be national Classification of Diseases (ICD-9) cod es after
ad op ted by hospitals before receiving fu ll paym ent for p atient d ischarge. The PSIs are listed in Table 9.5. While
services. Private insurers soon follow ed suit. SCIP m eas-
ures are listed in Table 9.4. In contrast to the m ore broad ly
d efined consensu s gu id elines, SCIP m easures have a strong
evid ence base. Whether or not this effort w ill be translated Table 9 .5 Agen cy for H ea lt h ca r e Resea r ch
into national im provem ent in resu lts rem ains to be d eter- a n d Q u a lit y (AH RQ ) p a t ien t sa fet y
mined . The JCO has also integrated certain SCIP m easu res in d ica t or s
into its evaluation requirem ents.
1. Hospital-level Patient Safety Indicators
Another im portant strategy em barked u pon by the CMS
• Complications of anesthesia
is know n as “nonpaym ent for hospital acqu ired cond i-
• Death in low mortality diagnosis related groups
tions,” otherw ise referred to as the “never event” policy. In • Decubitus ulcer
this strategy, the CMS has d eterm ined that it w ill not reim- • Failure to rescue
bu rse for flagrant med ical errors, such as w rong p atient, • Foreign body left in during procedure
w rong sid e, or w rong site surgery. Ad ministrators and sur- • Iatrogenic pneumothorax
• Selected infections due to medical care
• Postoperative hip fracture
• Postoperative hemorrhage or hematoma
Table 9 .4 Su r gica l ca r e im p rovem en t p rogr a m
• Postoperative physiologic and metabolic derangements
(SCIP)
• Postoperative respiratory failure
SCIP Process and Outcome Measures • Postoperative pulmonary embolism or deep vein thrombosis
• Postoperative sepsis
Infection (INF) • Postoperative wound dehiscence in abdominopelvic surgical
• SCIP INF 1: Prophylactic antibiotic received within one hour prior to patients
surgical incision • Accidental puncture and laceration
• SCIP INF 2: Prophylactic antibiotic selection for surgical patients • Transfusion reaction
• SCIP INF 3: Prophylactic antibiotics discontinued within 24 hours after • Birth trauma—injury to neonate
surgery end time (48 hours for cardiac patients) • Obstetric trauma—vaginal delivery with instrument
• SCIP INF 4: Cardiac surgery patients with controlled 6 a. m. postopera- • Obstetric trauma—vaginal delivery without instrument
tive blood glucose • Obstetric trauma—cesarean delivery
• SCIP INF 6: Surgery patients with appropriate hair removal 2. Area-level Patient Safety Indicators
• SCIP INF 7: Colorectal surgery patients with immediate postoperative • Foreign body left in during procedure
normothermia • Iatrogenic pneumothorax
Venous Thromboembolism (VTE) • Selected infections due to medical care
• SCIP VTE 1: Surgery patients with recommended venous thromboem- • Postoperative wound dehiscence in abdominopelvic surgical
bolism prophylaxis ordered patients
• SCIP VTE 2: Surgery patients who received appropriate venous throm- • Accidental puncture and laceration
boembolism prophylaxis without 24 hours prior to surgery to 24 hours • Transfusion reaction
after surgery • Postoperative hemorrhage or hematoma
useful inform ation can be obtained from this system , a d is- racy at transitions of care, (3) im p roved com m unication
ad vantage is that the d ata is obtained from m ed ical billing d u ring p atient care hand overs, (4) im p roved hand hygiene,
cod ers and m ay not accu rately reflect w hether a com p lica- and (5) p erform ance of the correct p roced u re at the correct
tion w as actu ally p reventable for not. An exam ple m ight be bod y site.
the PSI labeled “accid ental puncture and laceration.” An The WH O has focu sed on su rgical care sp ecifically
enterotom y m ad e d u ring the course of a d ifficult d issection throu gh a sep arate effort referred to as the “Safe Su rgery
in an irrad iated and m u ltiple-operated abd om en w ould fit Saves Lives” camp aign. One very tangible resu lt of this
into this category, and be interp reted by nonsu rgeons as effort is the Su rgical Safety Checklist, show n in Table 9.6
an “accid ent.” The surgeon w ho w as carefu lly d issecting (9). N ow being tested in eight cou ntries, the vision is that a
und er these circu m stances w ou ld d efinitely not agree. stand ard ized foru m for intraop erative com m u nication w ill
Desp ite su ch lim itations, the AH RQ PSIs w ill be p u blicly be ad op ted internationally, m u ch in the sam e w ay that the
rep orted as a safety ind icator by the governm ent next year. international aviation com mu nity has end orsed stand ard -
They alread y form the basis of certain p rop rietary safety ized flight checklists.
ind ices, su ch as those pu t forth by H ealthGrad es.com or
the University H ealth System Consortiu m .
■ IMPLEMENTATION STRATEGIES
■ EFFORTS FROM THE WORLD HEALTH While establishing a safe cu ltu re and em p hasizing an evi-
d ence base and consensu s gu id elines are im p ortant, ensur-
ORGANIZATION ing im p lem entation of w hat is know n to be safe p ractice is
Recognizing that patient safety shou ld be a global im pera- critical and m ay be the m ost d ifficu lt of all safety strategies
tive, the WH O, w orking w ith JCO, has em barked on an to accom p lish. Several strategies have been help ful in our
ambitiou s p roject to red u ce the incid ence of m ed ical errors environm ent.
internationally. One effort, know n as the “high 5’s” initia-
tive, focu ses on red u cing five p revalent types of m ed ical
errors, over a five-year period , in at least seven cou ntries.
■ ADDING PHARMACISTS TO ROUNDS
The id entified p roblem areas are (1) m anaging concen- Ou r m ed ical center is a tertiary care referral center;
trated injectable med icines, (2) assu ring m ed ication accu - the com p lexity of cases is high an d alw ays in creasin g.
Table 9 .6 Wor ld H ea lt h O r ga n iza t ion (W H O ) su r gica l sa fet y ch eck list

Before Induction of Anesthesia Before Skin Incision Before Patient Leaves Operating Room
SIGN IN TIME OUT SIGN OUT

• Patient Has Confirmed • Confirm All Team Members Have Introduced Nurse Verbally Confirms with the Team
• Identity Themselves by Name and Role • The Name Of The Procedure Recorded
• Site • Surgeon, Anesthesia Professional, and Nurse • That Instrument, Sponge and Needle Counts Are
• Procedure Verbally Confirm Correct (Or Not Applicable)
• Consent • Patient • How The Specimen Is Labeled (Including Patient
• Site Marked/Not Applicable • Site Name)
• Anesthesia Safety Check Completed • Procedure • Whether There Are Any Equipment Problems to be
• Pulse Oximeter on Patient and Anticipated Critical Events Addressed
Functioning • Surgeon Reviews: What Are the Critical or • Surgeon, Anesthesia Professional, and Nurse Review
Does Patient Have a: Known Allergy? Unexpected Steps, Operative Duration, the Key Concerns for Recovery and Management of
• No Anticipated Blood Loss? This Patient
• Yes • Anesthesia Team Reviews: Are There Any
Difficult Airway/Aspiration Risk? Patient-Specific Concerns?
• No • Nursing Team Reviews: Has Sterility
• Yes (Including Indicator Results) Been Confirmed?
Risk of 500 ml Blood Loss Are There Equipment Issues or Any Concerns?
(7 ML/KG in Children)? Has Antibiotic Prophylaxis Been Given Within the
• No Last 60 Minutes?
• Yes, and Adequate Intravenous Access • Yes
and Fluids Planned • Not Applicable
Is Essential Imaging Displayed?
• Yes
• Not Applicable
From World Health Organization. World Alliance for Patient Safety Progress Report 2006–2007. Geneva, Switzerland: WHO Press; 2008.
Transp lants, com p lex oncologic p roblem s, extracorp oreal ■ CREW RESOURCE MANAGEMENT
m em brane oxygenation (ECMO) patients, and others w ith
mu ltisystem organ failu re fill a large portion of ou r bed s. Another approach to the im p lem entation of safe practices
The p harm acologic asp ects of these cases are com p lex. is to ed u cate and train p hysicians and nu rses w ithin the
Ad d ing to the d ifficulty of m anaging such patients is the context of a team . The team is d efined , goals are set, and
ed u cational asp ect of our enterprise, w hich guarantees a ind ivid u al resp onsibilities are assigned . The com p letion of
constant su p p ly of new faces on round s. To ad d ress these tasks (or om ission) is apparent to m em bers of the team ,
issu es, and to p revent errors, w e have im plemented a p ol- w hich p rovid es a fail-safe stru ctu re. There has been consid -
icy of ad d ing a clinical pharm acist to each of ou r high com - erable interest in crew resou rce m anagem ent in the area of
plexity services. The role of this ind ivid ual is to su ggest m ed icine since it has been conclu sively show n to ad d valu e
app rop riate d ru gs, screen for allergies and incom p atibili- to aviation cockp it training. Crew resou rce m anagem ent is
ties, and m onitor for im p ortant sid e effects. The p rogram p robably best ap p lied in sm all w ell-d efined areas, w ith rel-
has been invaluable in im proving patient safety at ou r atively consistent staffing p atterns, su ch as an operating
institu tion and at others (10). room . In one rep ort a p eriop erative crew resou rce manage-
m ent training p rogram consisted of an e-learning m od u le,
the d evelopm ent of lam inated checklists and pocket-sized
■ RAPID RESPONSE TEAM card s, briefing scrip ts, a com m u nication w hiteboard , and
Mortality rates for in-hosp ital card iac arrest have been high a hand s-on training p rogram facilitated by exp erienced
for d ecad es, d esp ite ad vances in card iopu lm onary resu sci- p ersonnel. Even w ith focu sed effort at crew resou rce m an-
tation (CPR) techniqu es and card iotropic m ed ications. This agem ent, p eriop erative safety p ractice im plem entation
is tru e p articu larly for “floor arrests,” those cases of arrest w as fou nd to be less than p erfect, (12) bu t the field , at least
occu rring ou tsid e of the intensive care unit. In ou r center, in m ed icine, is in its infancy, and it w ill p robably be an
and m any others, analysis of CPR cases has led to allega- im p ortant p art of safety strategies in years to com e.
tions that insu fficient attention had been p aid to the
patient’s cond ition in the hours prior to the arrest, at a tim e ■ DEVELOPING COLLABORATIVE GROUPS
w hen interventions cou ld conceivably have been very
OF HOSPITALS
helpfu l.
One ap p roach to this p roblem has been to d evelop a When m otivated hosp itals join forces to d iscu ss safety, the
“rap id resp onse team ” (RRT), w hich is activated w hen cer- result is often a m ore consistent im plem entation of safety
tain p hysiologic p aram eters fall ou tsid e a sp ecified range. p ractices and better resu lts. The d evelop m ent of a collabo-
Su ch p aram eters id entified at ou r center are heart rate ( 40 rative grou p d irected at safety and / or qu ality allow s for
or 140 w ith new sym ptom s), respiratory rate ( 8 or 36), com p arative evalu ation of qu ality and safety and often
blood p ressure (BP systolic 80 or 220, BP d iastolic 110 resu lts in a sp irit of friend ly com p etition, w hich im proves
w ith sym p tom s) and u nexp lained change in cognition or the aggregate level of safety.
neu rologic statu s of ad ult inpatients. A key featu re of the A p rom inent exam p le of su ch collaboration w as m en-
RRT activation is that it is seen as m and atory for nu rsing; tioned p reviou sly, the Michigan H osp ital Association spon-
no ju d gm ent is requ ired . If the param eters are exceed ed , sored Keystone Initiative. H ere evid ence-based practice for
the RRT is activated . This relieves som e of the anxieties the care of patients in the intensive care unit (ICU) w as
experienced by nursing in the past about com m u nication m onitored and fou nd to be low across the state. A p rotocol
w ith p hysicians, particu larly at od d hours. In ou r center, w as ad op ted for over 100 ICU grou p s w hich inclu d ed ele-
activation of RRT resu lts in the tim ely arrival of an exp eri- vation of the head of the bed to 30o angle, u lcer prophy-
enced su rgical intensive care u nit (SICU) nu rse and a respi- laxis, regu lar resp iratory w eaning trials, and a central line
ratory therap ist. If the cond itions are fou nd to w arrant it, a insertion protocol with line maintenance involving chlorhex-
hosp italist is called . This occurs in 15% of cases. There is id ine p atches. When the latter p rotocol w as im plem ented a
controversy in the literatu re as to w hether the RRT effort p rofound d rop in the incid ence of BSI across the state w as
actu ally is effective (11). H ow ever, the concept has so m u ch seen, and the estim ated cost savings exceed ed 160 m illion
face valid ity that m ost hospitals have accepted it as an d ollars (6).
im portant strategy to prom ote a safety cu lture. In a d ifferent exam p le, 34 Michigan hosp itals form ed
An interesting and entirely u nexpected offshoot of the the Michigan Su rgical Qu ality Collaborative. These hosp i-
RRT has been the process, by the RRT team , of visiting tals, u sing the Am erican College of Su rgeons-N ational Su r-
nu rsing floors on a shift-by-shift basis prior to any RRT gical Quality Im provem ent Project (ACS-N SQIP) as a
activation. This p rocess lets the team become m ore fam iliar qu ality rep orting infrastru ctu re, convene at 3-m onth inter-
w ith p atients w ho m ight su bsequ ently w arrant RRT activa- vals to share inform ation abou t su rgical resu lts. H ospitals
tion. Visits often foster a d iscu ssion am ong caregivers and w ith the few est com plications in a sp ecific area d iscuss
fam ily as to w hether any intervention is ap propriate or w hy they feel they have been su ccessfu l. “Best p ractices”
w arranted . are then d istribu ted in a netw ork inclu d ing the Internet, a
hard cop y new sletter, and You Tube. Each hosp ital im p le- ble to com p are the safety of d ifferent hosp itals if the d efini-
ments strategies it feels are appropriate for its situation. tions are not stand ard ized . Many national organizations
The resu lt has been a sharp d rop in the incid ence of su rgi- are w orking on this top ic. The WH O has recently d evel-
cal com p lications. The results suggest that a collaborative op ed an “International Classification for Patient Safety”
qu ality organization, w ith regular and intensive sharing of d esigned to “d efine, harm onize and grou p p atient safety
d ata and best p ractices, is an essential vehicle for qu ality concep ts into an internationally agreed u p on classification
im provem ent. in a w ay that is cond u cive to learning and im p rove patient
safety across system s.” This w ork, w hile d ifficu lt, is essen-
■ PATIENT AND FAMILY INVOLVEMENT tial for the p atient safety m ovem ent (9).
One elem ent of the p atient safety m ovem ent that w ill
becom e m ore im p ortant in the fu tu re is the involvem ent ■ PUBLIC REPORTING OF SAFETY DATA
of the p atient in variou s hosp ital safety strategies. A valu - We live in an age of transp arency. The p u blic w ants and
able sou rce of inform ation, and an im p ortant feed back d eserves inform ation abou t the safety record of a given
m echanism , is lost w hen the p atient, or the fam ily, is not a hosp ital. And yet su ch inform ation is hard to find . The
p art of the care p rocess. Tw o exam p les of the valu e of fu tu re of the p atient safety m ovem ent d ep end s u p on the
p atient involvem ent involve hand w ashing and u rgent d evelop m ent of an effective safety rep orting m echanism .
care. This is becau se, in the absence of a large-scale d atabase,
For hand w ashing, an effective hospital strategy inform ation is not d issem inated effectively, and one hospi-
prom p ts p atients to ask physicians “have you w ashed you r tal may easily m ake the sam e m istake as its sister hospital
hand s?” w hen they com e into the patient’s room . Physi- d ow n the street. One m ajor im p ed im ent to the d evelop-
cians frequ ently w ear bu ttons in this effort, w hich say, m ent of a national safety d atabase is the lack of a stand ard -
“Ask m e if I’ve w ashed m y hand s.” While it m ay seem triv- ized taxonom y of p atient safety events. This p roblem is
ial, and som ew hat d em eaning to the physicians, the fact being ad d ressed , as d escribed earlier.
rem ains that the p ercentage of p hysicians and nu rses Pu blic rep orting has been initiated u sing both volu n-
w ashing hand s p rior to the p atient contact remains far tary and m and atory d esigns. Tw o exam p les of su ccessful
below 100%, and the prevalence of patient infection w ith voluntary reporting systems are the N ational N osocom ial
Clostrid iu m d ifficile, vancom ycin-resistant enterococci, Infection Su rvey, a branch of the Centers for Disease Con-
and other hosp ital-acqu ired infections rem ains high. In this trol, and the Med MARX p rogram of the U. S. Pharm a-
context, p atient involvem ent could be seen as a very cop eia. Mand atory safety rep orting system s are often
im portant piece of Sw iss cheese. state-initiated and im pose variou s sanctions on hospitals
Another exam ple of patient and fam ily involvem ent in know n to be engaged in u nsafe p ractices. This p enalty pro-
the care p rocess is the concept of “fam ily activation” of the vid es a d isincentive to rep ort, how ever. Only a few states
RRT. Fam ily m em bers are often m ore aw are of changes in a have su ccessfu l m and atory rep orting system s.
patient’s cond ition than nurses or d octors, for the obviou s One very su ccessfu l exam p le of a volu ntary rep orting
reason that they know the p ersonality and traits of the system , albeit in the field of aviation, is the Aviation Safety
patient in d etail. “H e w ould n’t com plain about this u nless Rep orting System . This system analyses 30,000 rep orts
it w as really bad ” is an im portant sou rce of inform ation annu ally. Its su ccess has d ep end ed on these factors: the sys-
from a w ife. In the p ast, this clue to an evolving situ ation tem is sim p le, it is safe (for the rep orting p ilots), and it pro-
w as som etim es lost on caregivers m ore focu sed on vital vid es valu e (13). The p atient safety m ovem ent w ould d o
signs and u rine ou tp u t. In “fam ily activation” of the RRT, w ell to em u late this system . When it d oes, and once the
fam ily m em bers are allow ed to call a phone nu m ber acti- taxonom y is stand ard ized , d octors, nu rses, and ad m inis-
vating the RRT if they feel that m ore attention is need ed to trators w ill be consid erably m ore w illing to m ake safety
a given situ ation. While it m ight seem that this w ou ld let d ata available to the p u blic.
loose a flood of su ch calls, in actu ality this has not been
the case.
■ REFERENCES
■ DEVELOPING A TAXONOMY 1. Kohn, LT, Corrigan JM, Donald son, M. ed s. To err is human: building a
safer health system. Washington, DC: N ational Acad em y Press; 2000.
FOR PATIENT SAFETY 2. Reason J. Ed u cation and d ebate. H u m an errors: m od els and m anage-
m ent. BMJ 2000;320:768–770.
Ultim ately, com p arative d ata on the safety of patient care 3. Ely JW, Levinson W, Eld er N C, et al. Perceived cau ses of fam ily p hysi-
cians’ errors. J Fam Pract 1995;40:337–344.
in this cou ntry w ill be available to the public, mu ch in the
4. Singh H , Thom as E, Petersen L, et al. Med ical errors involving trainees:
sam e w ay that the safety of retail prod ucts, med ications, a stud y of closed m alpractice claim s from 5 insu rers. Arch Intern Med
and autom obiles are cu rrently rep orted . For any reporting 2007;167(19):2030–2036.
5. Boothm an RC, Blackw ell AC, Cam p bell DA Jr, et al. A better ap p roach
system to be valu able and fair, the d efinitions of safety
to m ed ical m alpractice claim s? The University of Michigan Experience.
events need to be refined and agreed u pon. It is not p ossi- J Health Life Sci Law 2009;2(2):125–159.
6. Pronovost P, N eed ham D, Berenholtz S, et al. An intervention to 10. Kucu karslan SN , Peters MP, Mlynarek M, et al. Pharm acists on rou nd -
d ecrease catheter-related blood stream infections in the ICU. N Eng J ing team s red u ce preventable ad verse d ru g events in hospital general
Med 2007;356(25):2660. m ed icine u nits. Arch Intern Med 2003;163:2014–2018.
7. Ovretveit J. Which interventions are effective for improving patient safety? A 11. MERIT Stud y Investigators. Introd u ction of the m ed ical em ergency
synthesis of research and policy issues. WHO H EN Copenhagen and MMC, team (MET) system : a clu ster-rand om ised controlled trial. Lancet 2005;
Karolinska, Stockholm . Available at: http :/ / hom ep age.m ac.com . 365:2091–2097.
8. POISE Stu d y Grou p . Effects of extend ed -release m etop rolol su ccinate 12. France D, Lem in g L, Jackson T. An observation al analysis of
in patients und ergoing noncard iac surgery (POISE trial): a rand om ized su rgical team com p liance w ith p eriop erative safety p ractices
controlled trial. Lancet 2008;371:1839–1847. after crew resou rce m an agem ent trainin g. Am J Surg 2008;195:546–
9. World H ealth Organization. World Alliance for Patient Safety Progress 553.
Report 2006–2007. Geneva, Sw itzerland : WH O Press; 2008. 13. Leape L. Rep orting of ad verse events. N Engl J Med 2002;347:163.
PART
II
Management of Surgical
Complications
CHAPTER
10
Assessment of Perioperative
Cardiac Risk
Debabrata Mukherjee and Kim A. Eagle
■ INTRODUCTION lem s, and the severity of d isease is u sed to m od ify its

im p ortance. Risk m arkers recognized as pred ictive of
In the United States, approximately 25 million patients increased p erioperative risk (4–7) inclu d e p oor functional
und ergo noncardiac surgery annually. Of these, nearly capacity, and prior history or electrocard iographic evid ence
50,000 patients suffer perioperative myocardial infarction of coronary artery d isease, congestive heart failure, arrhyth-
(MI), and m ore than half of 40,000 perioperative d eaths are mia, valvu lar heart d isease, d iabetes mellitu s, uncontrolled
caused by card iac events (1,2). Most perioperative card iac systemic hypertension, renal insufficiency, and stroke.
morbid ity and mortality is related to m yocard ial ischemia, Id entifying several features on physical exam ination
congestive heart failure, or arrhythmias. Therefore, preoper- m ay be u sefu l in assessm ent of p eriop erative risk. Patients
ative evaluation and management to reduce morbidity and w ith u ncontrolled system ic hyp ertension shou ld be id enti-
mortality rates emphasize the d etection, characterization, fied and treated . Becau se congestive heart failu re and
and treatment of coronary artery disease, left ventricular valvu lar heart d isease are associated w ith increased risk,
(LV) systolic d ysfunction, abnormal valve function, and sig- p hysical find ings su ggestive of these d iagnoses should be
nificant arrhythm ias. The purpose of preoperative evalua- sou ght. The p hysical exam ination shou ld cover general
tion is not to “clear” patients for surgery but to assess appearance (cyanosis, pallor, dyspnea during conversation/
med ical status and card iac risks posed by the surgery m inim al activity, Cheyne-Stokes resp iration, poor nu tri-
planned, and recommend strategies to reduce risk. There are tional statu s, obesity, skeletal d eform ities, trem or, and anx-
tw o goals of the preoperative evaluation: first, to identify iety), blood p ressu re in arm s, carotid p u lses, extrem ity
patients at increased risk of an adverse perioperative card iac p u lses, and ankle-brachial ind ices. Ju gu lar venou s pressure
event and, second, to modify cardiac risk to improve short- and p ositive hep atoju gu lar reflex are reliable signs of vol-
term and long-term clinical outcomes. This chapter review s u m e overload in chronic heart failu re, and p u lm onary rales
preoperative identification of risk markers, opportunities for and chest X-ray evid ence of p u lm onary congestion corre-
mod ifying risk, early id entification of post-operative com- late better w ith acu te heart failu re. Patients w ith aortic
plications, and management of such complications. Its pri- stenosis can be id entified by a typ ical m u rm u r and w hen
mary focus is on coronary artery and coronary heart d isease accom p anied by a d im inished and d elayed u pstroke of the
since these problems d ominate the clinical land scape. carotid or brachial p u lse. Finally, the p resence of carotid or
other vascu lar bru its help s id entify p atients at increased
■ IDENTIFICATION OF RISK MARKERS risk of harboring occu lt coronary artery d isease.
The typ e of su rgery also has im p ortant im p lications for
The majority of patients at increased risk of ad verse periop-
card iac risk, and su rgical p roced u res generally can be clas-
erative card iac events can be id entified u sing a sim p le
sified as having high, interm ed iate, and low card iac risk
bed sid e or office assessm ent. A carefu l history, physical
based u p on the likely d egree and d u ration of hem od y-
exam ination, and review of the resting 12-lead electrocar-
nam ic stress d u ring su rgery and the p otential correlation of
d iogram (ECG/ EKG) are usually sufficient to allow stratifi-
the op eration (e.g. vascu lar su rgery) w ith concomitant
cation of most patients into low, intermed iate, or high-risk
coronary or other heart d isease (Table 10.2). Patients at very
categories for an ad verse perioperative card iac event. Risk
low clinical risk and those at high clinical risk of an ad verse
markers for ad verse post-operative outcomes can be strati-
p eriop erative card iac event typ ically can be id entified
fied as major, interm ed iate, and m inor (Table 10.1) (3).
u sing clinically available featu res d escribed above. Patients
Greater w eight is given for active than for quiescent prob-
at low clinical risk generally requ ire no ad d itional testing
p rior to noncard iac su rgery. Am ong p atients u nd ergoing
Debabrata Mukherjee: Texas Tech University H ealth Sci- elective noncard iac surgery in w hom risk is d eterm ined to
ences Center, EL Paso, TX 79905. be interm ed iate or high, ad d itional testing m ay be useful to
Kim A. Eagle: University of Michigan, Ann Arbor, MI better d efine risk (3). It is u sefu l to em p loy a stepw ise
48109. ap p roach to the p reop erative assessm ent of card iac risk as
67
68 Part II • Management of Surgical Complications
Table 1 0 .1 Clin ica l p r ed ict or s of in cr ea sed p er iop era t ive ca rd iova scu la r r isk
• Major predictors
• Unstable coronary syndromes
• Unstable or severe angina (CCS class III or IV)a
• Recent MIb
• Decompensated HF (NYHA functional class IV; worsening or new-onset HF)
• Significant arrhythmias (High-grade atrioventricular block; Mobitz II atrioventricular block; Third-degree atrioventricular heart block; Symptomatic ven-
tricular arrhythmias; Supraventricular arrhythmias (including atrial fibrillation) with uncontrolled ventricular rate (Heart rate 100 bpm at rest); Sympto-
matic bradycardia; Newly recognized ventricular tachycardia
• Severe valvular disease (Severe aortic stenosis [mean pressure gradient greater than 40 mm Hg, aortic valve area less than 1.0 cm2, or symptomatic];
Symptomatic mitral stenosis (progressive dyspnea on exertion, exertional presyncope, or HF)
• Intermediate predictors
• History of ischemic heart disease
• History of compensated or prior HF
• History of cerebrovascular disease
• Diabetes mellitus
• Renal insufficiency (Creatinine 2.0 mg/dL)
• Minor predictors
• Advanced age
• Abnormal ECG (left ventricular hypertrophy, left bundle branch block, ST–T abnormalities)
• Rhythm other than sinus (e.g., atrial fibrillation)
• Uncontrolled systemic hypertension
MI, myocardial infarction; HF, heart failure; ECG, electrocardiogram; CCS, Canadian cardiovascular class; NYHA, New York Heart Association.
a
May include stable angina in patients who are usually sedentary.
b
Recent myocardial infarction is defined as occurring within a period greater than seven days but less than or equal to one month; acute myocardial infarction is within seven
days.
Adapted from Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 Guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: executive
summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on
Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in collaboration with the American Society of Echocardiography, American Society of Nuclear
Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and
Biology, and Society for Vascular Surgery. Circulation 2007;116:1971–1996.
suggested by the American College of Cardiology/ American careful hem od ynamic assessment may still be appropriate,
H eart Association (ACC/ AH A) gu id elines (Fig. 10.1). albeit w ith a heightened risk of perioperative d eath w ith a
mortality risk of approximately 10% (9,10).
■ Management of specific cardiovascular Mitral stenosis can usually be medically managed with
conditions heart rate control, w hen mild and asymptomatic. Severe
mitral stenosis should be corrected to prolong survival and
Valvular Heart Disease patient complications, unrelated to the proposed noncardiac
Severe aortic stenosis [valve area 1.0 cm (2) or mean pres- surgery, in accord ance w ith ACC/ AH A guidelines on man-
sure grad ient greater than 40 mm H g] presents the greatest agement of vascular heart disease. In general, aortic and
valve-associated card iovascular risk for patients und ergo- mitral regurgitation lesions are better tolerated periopera-
ing noncard iac surgery (3). The presence of a fixed obstruc- tively than stenotic lesions. Med ical regim ens for these
tion to LV outflow d ramatically limits functional card iac ind ividuals should be optimized pre-operatively with
reserve and may be associated w ith intracavitary LV pres- diuretics and afterload reduction with vasodilators. Appro-
sures in excess of 300 mm H g. Accompanying LV hypertro- priate prophylaxis for bacterial end ocarditis is indicated in
phy pred isposes the patient to d iastolic d ysfu nction and patients with valvular heart d isease and prosthetic heart
pulmonary congestion. In general, severe and / or sympto- valves. Appropriate perioperative antithrombotic therapy for
matic aortic stenosis should be ad d ressed prior to the patients w ith prosthetic heart valves is outlined in Table 10.3.
patient u nd ergoing elective noncard iac su rgery. In most
cases, aortic valve replacement is ind icated as the d efinitive Cardiac Arrhythmias
therapy of choice (8). If card iac surgery is contraind icated , In ind ivid u als w ith arrhythm ias, a m etabolic p rofile and
percu taneou s aortic balloon valvotomy can be used to miti- the list of m ed ications shou ld be carefu lly review ed and
gate a LV outflow obstruction, even if only as a tem porizing corrected . Even m ild hyp okalem ia shou ld be corrected in
measure. When neither surgery nor percutaneous aortic these ind ivid u als. Su stained or sym p tom atic ventricu lar
valvotomy is consid ered feasible, noncard iac surgery w ith arrhythm ias shou ld be treated w ith su p p ressive therapy.
Chapter 10 • Assessment of Perioperative Cardiac Risk 69
Table 1 0 .2 Ca rdiac risk a stratifi ca tion for ■ Diagnostic testing

differen t types of su rgical procedu res Rou tine laboratory tests su ch as seru m creatinine, hem o-
globin, p latelet cou nt, p otassiu m level, liver profile, and
• High risk, Vascular (Reported cardiac riska 5%)
• Aortic and other major vascular surgery
oxygen satu ration are im p ortant in risk stratification. Arte-
• Peripheral vascular surgery rial blood gas analysis is u sefu l in p atients w ith ad vanced
• Intermediate risk (Reported cardiac risk 1%–5%) p u lmonary d isease. A 12-lead ECG p rovid es im portant
• Intraperitoneal and intrathoracic p rognostic inform ation. Patients w ho are at low risk based
• Carotid endarterectomy on history, p hysical exam ination, and rou tine laboratory
• Head and neck surgery tests m ay not need fu rther evalu ation. N oninvasive testing
• Orthopedic surgery is p rimarily u sefu l in interm ed iate risk p atients. The p eri-
• Prostate surgery op erative gu id elines are straightforw ard on recom m end a-
• Low riskb (Reported cardiac risk 1%) tions for p atients abou t to u nd ergo em ergency surgery, the
• Endoscopic procedures p resence of p rior card iac revascu larization, and the occur-
• Superficial biopsy
rence of m ajor card iac p red ictors. H ow ever, the m ajority
• Cataract
• Breast surgery
of p atients have either interm ed iate or m inor clinical p re-
d ictors of increased p eriop erative card iovascu lar risk.
a
Combined incidence of cardiac death and nonfatal myocardial infarction. Table 10.4 p resents the cu rrently recom m end ed approach
b
Do not generally require further preoperative cardiac testing for noninvasive testing before noncard iac su rgery. In a
Adapted from Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 p atient w ith an interm ed iate clinical p red ictor, the presence
Guidelines on perioperative cardiovascular evaluation and care for noncardiac
surgery: executive summary: a report of the American College of Cardiology/
of either a low fu nctional cap acity or high su rgical risk
American Heart Association Task Force on Practice Guidelines (Writing Committee should lead the physician to consid er noninvasive testing.
to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for In the absence of interm ed iate clinical p red ictors, noninva-
Noncardiac Surgery): developed in collaboration with the American Society of sive testing shou ld be consid ered w hen both the su rgical
Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, risk is high and the fu nctional cap acity is low. Clinical pre-
Society of Cardiovascular Anesthesiologists, Society for Cardiovascular
Angiography and Interventions, Society for Vascular Medicine and Biology, and
d ictors are d efined in Table 10.1.
Society for Vascular Surgery. Circulation 2007;116:1971–1996. In m ost am bu latory p atients, the test of choice is exer-
cise ECG testing, w hich can p rovid e an estim ate of both
fu nctional cap acity and d etect m yocard ial ischem ia
throu gh changes in the ECG and hem od ynam ic response.
Patients w ith sym ptom atic brad yarrhythmias shou ld be The ability to exercise m od erately beyond 4 to 5 m etabolic
treated w ith tem porary pacing and a p erm anent p ace- equ ivalents (METs) w ithou t sym p tom s d efines low risk.
m aker im p lanted w hen ind icated . If an ind ivid ual alread y Patients w ho can achieve 85% of m axim u m pred icted
has a p erm anent p acem aker, this should be checked p rior heart rate w ithou t EKG changes are at low est risk. Patients
to su rgery. Electrocau tery shou ld be minim ized in p atients w ith an abnorm al EKG resp onse at greater than 70% of pre-
w ho are totally pacem aker d epend ent and p acem akers d icted heart rate are at interm ed iate risk and those w ith
checked again after su rgery to ensu re settings are op tim al. abnorm al EKG resp onse at less than 70% of p red icted heart
Typ ically, im p lanted d efibrillators are tu rned off d u ring rate are at highest risk. It m u st be em p hasized that
surgery and tu rned back on after surgery. althou gh rou tine EKG stress testing has the sensitivity to
id entify one vessel coronary artery d isease (CAD) of ju st
Hypertension 55% to 60%, its sensitivity for left m ain or ad vanced three
Mild to m od erate hypertension shou ld be m anaged w ith vessel d isease is far higher, in the 85% to 90% range. Thus,
m ed ical therap y and closely m onitored d u ring su rgery. for the p u rp oses of id entifying the highest risk p op u lation,
Ind ivid u als w ith severe hypertension (d iastolic 110 m m ) it is qu ite reasonable.
need control p rior to surgery. For urgent su rgery in In p atients w ith im p ortant abnorm alities on their rest-
p atients w ith severe hypertension, intravenou s agents m ay ing ECG (e.g., left bu nd le-branch block, LV hypertrophy
be u sed to achieve control of blood pressure. Abru p t w ith- w ith “strain” p attern, or d igitalis effect), other techniqu es
d raw al of beta-blockers and clonid ine shou ld be avoid ed to su ch as exercise echocard iograp hy, exercise m yocard ial
p revent rebound hyp ertension. p erfu sion im aging, or p harm acological stress im aging m ay
be ind icated . Pharm acological stress or p erfu sion im aging
Cardiomyopathy is ind icated in p atients u nd ergoing orthop ed ic, neurosurgi-
Pu lm onary artery catheters m ay be beneficial in patients cal, or vascu lar su rgery w ho are u nable to exercise or have
w ith severe LV d ysfu nction. Close monitoring of the vol- left bu nd le branch block (LBBB)/ p aced rhythm . The sensi-
u m e statu s, heart rate, and system ic vascu lar resistance in tivity and specificity of exercise thalliu m scans in the pres-
ind icated in p atients w ith hyp ertrop hic card iom yop athy. ence of left bu nd le-branch block are low, and overall
Intravascular volum e d ep letion is p oorly tolerated in these d iagnostic accu racy varies from 36% to 60% (11,12). In con-
p atients and m ay result in card iogenic shock. trast, the u se of vasod ilator [d ip yrid amole/ ad enosine]
Pe riope ra tive s urve illa nce

Ne e d for e me rge ncy a nd pos tope ra tive ris k
S te p 1 Ye s Ope ra ting room
nonca rdia c s urge ry? s tra tifica tion a nd ris k fa ctor
(Cla s s I, LOE C)
ma na ge me nt
No
Active ca rdia c Eva lua te a nd tre a t pe r Cons ide r

S te p 2 Ye s
conditions a ACC/AHA guide line s ope ra ting room
(Cla s s I, LOE B)
No
P roce e d with
S te p 3 Low ris k s urge ry Ye s
pla nne d s urge ry
(Cla s s I, LOE B)
No
Good functiona l ca pa city (MET leve l

P roce e d with
S te p 4 gre a te r tha n or e qua l to 4) without Ye s
pla nne d s urge ry
s ymptoms (Cla s s I, LOE B)
S te p 5 No or unknown
1 or 2 clinica l
3 or more clinica l ris k fa ctors c
ris k fa ctors ‡ No clinica l
ris k fa ctors ‡
Inte rme dia te
Va s cula r s urge ry
ris k s urge ry Inte rme dia te ris k
Va s cula r s urge ry s urge ry Cla s s I,
Cla s s IIa , LOE B
LOE B
Cons ide r te s ting if it will P roce e d with pla nne d s urge ry with HR controld (Cla s s IIa , LOE B) P roce e d with
cha nge ma na ge me ntb or cons ide r noninva s ive te s ting (Cla s s IIb, LOE B) if it will cha nge ma na ge me nt pla nne d s urge ry
FIGURE 10.1. Cardiac evaluation and care algorithm for noncardiac surgery based on active clinical conditions, known cardiovascu-
lar disease, or cardiac risk factors for patients 50 years of age or greater. a See Table 10.1 for active clinical conditions. bNoninvasive test-
ing may be considered before surgery in specific patients with risk factors if it will change management. c Clinical risk factors include
ischemic heart disease, compensated or prior heart failure, diabetes mellitus, renal insufficiency, and cerebrovascular disease. dCon-
sider perioperative beta blockade for populations in which this has been shown to reduce cardiac morbidity/mortality. ACC/AHA, Ameri-
can College of Cardiology/American Heart Association; HR, heart rate; LOE, level of evidence; MET, metabolic equivalent. Adapted from
Fleisher LA, Beckman J A, Brown KA, et al. ACC/AHA 2007 Guidelines on perioperative cardiovascular evaluation and care for noncardiac
surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guide-
lines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in
collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of
Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biol-
ogy, and Society for Vascular Surgery. Circulation 2007;116:1971–1996.
nu clear stress testing in su ch p atients has a sensitivity of stressor in p atients w ith seriou s arrhythm ias or severe
98%, a sp ecificity of 84%, and a d iagnostic accuracy of 88% hypertension or hypotension. For patients in w hom echocar-
to 92% (13–15). Thu s, in patients w ith LBBB, d ipyrid am ole d iographic image quality is likely to be poor, a myocardial
or ad enosine-thalliu m im aging is the p referred m ethod . perfusion study is more appropriate. If there is an additional
In p atients u nable to perform ad equate exercise as w ith question about valvular d iseases, the echocard iographic
m ost p atients w ith peripheral vascu lar d isease (PVD), a stress test may be more useful. In many instances, either
nonexercise stress test should be used . In this regard , stress perfusion or stress echocard iography is appropriate.
d ip yrid am ole m yocard ial p erfu sion im aging testing and In a meta-analysis of d obutamine stress echocard iography,
d obu tam ine echocard iograp hy are the m ost com m only ambulatory electrocard iography, rad ionu clid e ventricu log-
u sed tests. Intravenous d ipyrid am ole shou ld be avoid ed in rap hy, and d ip yrid am ole thalliu m scanning in p red icting
patients w ith significant bronchosp asm , critical carotid d isad verse card iac ou tcom e after vascu lar su rgery, all tests
ease, or a cond ition that prevents w ithd raw al from theo- had a sim ilar p red ictive valu e, w ith overlap p ing confi-
phylline p rep arations. Dobutam ine should not be u sed as a d ence intervals (16). Another m eta-analysis of 15 stu d ies
Table 1 0 .3 An t it h r om bot ic t h era py in t h e u tility of d ip yrid am ole thalliu m im aging in the preopera-
p er iop era t ive set t in g in p a t ien t s w it h tive assessm ent of card iac risk in p atients w ith p erip heral
p rost h et ic h ea r t va lves vascu lar d isease. Forty-eight p atients w ith su spected CAD
w ere evalu ated before they u nd erw ent vascu lar su rgery;
• Very low risk surgery (dental work, superficial biopsy) sixteen of these p atients had thalliu m red istribu tion. All
• Briefly reduce the INR to low or subtherapeutic range and resume eight perioperative card iac events occu rred in patients w ho
normal dose post-procedure had p reop erative thalliu m red istribu tion. Lep po et al. (19)
• High risk for thrombosis [recent ( 1 year) thromboembolism, Bjork p erform ed d ip yrid am ole thalliu m im aging in 100 consecu-
Shiley valve especially in mitral position, or 3 of the following risk
tive p atients ad m itted for elective p erip heral vascu lar
factors: A Fib, previous embolism, hypercoagulable condition, mechan-
su rgery and d eterm ined that the p resence of thalliu m
ical prosthesis and LVEF 30%]
• Stop warfarin 72 hours prior to procedure red istribu tion w as the m ost significant p red ictor of seriou s
• Start heparin when INR 2.0 nonfatal MI or card iac d eath. The od d s for a seriou s card iac
• Stop heparin 6 hours after the procedure event w ere 23 tim es greater in a p atient w ith thallium
• Restart heparin within 24 hours and continue until INR 2.0 red istribu tion than in a patient w ithou t red istribution,
• Approach for patients between these two extremes strongly su ggesting that m yocard ial im aging m ay be u sed
• Physicians must assess the risk and benefit of reduced anticoagula- as a p rim ary screening test before elective vascu lar su rgery
tion versus perioperative heparin therapy (19). The find ings of these early p ap ers have been con-
firm ed by many su bsequ ent stu d ies. A m eta-analysis by
A Fib, atrial fibrillation; LVEF, left ventricular ejection fraction INR, International
Normalized Ratio.
Shaw et al. (17) analyzed the resu lts of 10 articles and 1,994
Adapted from Eagle KA, Berger PB, Calkins H, et al. ACC/AHAguideline update for vascu lar su rgery cand id ates over a 9 year p eriod . Card iac
perioperative cardiovascular evaluation for noncardiac surgery–executive summary: a d eath or nonfatal MI occu rred in 1%, 7%, and 9% of
report of the American College of Cardiology/American Heart Association Task Force p atients w ith norm al resu lts, fixed d efects, and reversible
on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Car- d efects on thalliu m scans, resp ectively, d em onstrating the
diovascular Evaluation for Noncardiac Surgery). J Am Coll Cardiol 2002;39:542–553.
u tility of d ip yrid am ole-thalliu m scintigrap hy for preopera-
tive risk stratification.
d em onstrated that the prognostic valu e of noninvasive The extent and severity of p erfu sion d efects p lay a sig-
stress im aging abnorm alities for p eriop erative ischem ic nificant role in ad verse p eriop erative events, as the m ore
events is comp arable for the available techniques but the extensive the perfusion abnorm alities or the find ing of cav-
accu racy varies w ith CAD p revalence (17). The exp ertise of ity d ilation or thalliu m lu ng u p take, the w orse the periop-
the local laboratory in id entifying ad vanced coronary d is- erative p rognosis. Althou gh the im med iate p urpose of
ease is qu ite im portant in choosing the approp riate test. p reop erative exam ination is to assess the risk associated
Dip yrid am ole thalliu m stress testing to risk-stratify w ith the p lanned su rgical p roced u re, the d eterm ination of
patients w ith su spected CAD is particu larly effective a long-term p rognosis m ay be valu able in the overall m an-
before vascu lar su rgery. Bou cher et al. (18) reported on the agem ent of a p atient w ith know n or su sp ected coronary
Table 1 0 .4 G u id e t o n on in va sive t est in g in p r eop era t ive p a t ien t s

• Class I (is recommended)
1. Patients with active cardiac conditions (see Table 10.1) in whom noncardiac surgery is planned should be evaluated and treated before noncardiac
surgery.
• Class IIa (is reasonable)
1. Noninvasive stress testing of patients with 3 or more clinical risk factors and poor functional capacity (less than 4 METs) who require vascular sur-
gery is reasonable if it will change management.
• Class IIb (may be considered)
1. Noninvasive stress testing may be considered for patients with at least 1 to 2 clinical risk factors and poor functional capacity (less than 4 METs)
who require intermediate-risk or vascular surgery if it will change management.
• Class III (not recommended)
1. Noninvasive testing is not useful for patients with no clinical risk factors undergoing intermediate-risk noncardiac surgery.
2. Noninvasive testing is not useful for patients undergoing low-risk noncardiac surgery.
METs, metabolic equivalents; Emergency major operations may require immediately proceeding to surgery without sufficient time for noninvasive testing or preoperative
interventions.
artery d isease. By u sing ad enosine-sestam ibi stress im ag- ■ Combined clinical and scintigraphic assessment
ing, clinicians can assess both perfusion as w ell as regional
and overall LV fu nction. Thus, this form of nu clear card iac Although the sensitivity of d ipyrid am ole thalliu m im aging
im aging has largely su p ersed ed thalliu m im aging. for d etecting p atients at increased risk is excellent, one of
Dobu tam ine stress echocard iograp hy has also been its lim itations for p reop erative screening is its low sp eci-
u sed su ccessfu lly to id entify patients at risk for card iac ficity and p ositive p red ictive valu e. In ord er to im prove the
com plications of su rgery, w ith very high negative pred ic- valu e of risk stratification, m any rep orts have su ggested
tive valu es. In a m eta-analysis, patients w ith no d obu ta- u tilization of the com bination of clinical m arkers and non-
m ine-ind u ced w all m otion abnorm alities had a very low invasive test resu lts. Eagle et al. (21) first rep orted on
event rate (0.4%), com pared w ith a 23.4% event rate in u sing assessm ent of clinical m arkers (history of angina, MI,
p atients w ho d eveloped new w all m otion abnorm alities congestive heart failu re, d iabetes, and Q w ave on ECG)
d u ring d obu tam ine infusion. Dobutam ine stress echocar- and thalliu m red istribu tion to id entify a low risk su bset of
d iograp hy has also been show n to have p rognostic valu e p atients. The au thors d em onstrated that p atients w ithout
for p red icting late events after vascu lar su rgery. Fu rther- any of these clinical m arkers d id not requ ire d ip yrid am ole
m ore, as for d ip yrid am ole thallium im aging, the m ost u se- thalliu m testing. H ow ever, thalliu m red istribu tion had a
fu l role for stress echocard iograp hy ap p ears to be in significant p red ictive valu e in p atients w ith—one or tw o
p atients at interm ed iate clinical risk. clinical risk factors. Within this grou p , tw o of 62 (3.2%; 95%
For p atients at high risk, it m ay be appropriate to p ro- CI, 0% to 8%) p atients w ithou t thalliu m red istribu tion had
ceed w ith coronary angiograp hy rather than p erform a events com p ared w ith 16 events in 54 p atients (29.6%; 95%
noninvasive test. For high-risk patients w ith contraind ica- CI, 16% to 44%) w ith thalliu m red istribu tion (21). L’Italien
tions to angiograp hy or coronary revascularization, m ed - et al. (22) rep orted the resu lts of a Bayesian m od el for peri-
ical therap y w ith aggressive beta-blockad e m ay be the op erative risk assessment w hich com bined clinical vari-
correct ap p roach (20). In patients w ith u nstable angina or ables w ith d ip yrid am ole thalliu m find ings. This analysis
evid ence of resid u al ischem ia after recent MI, d irect coro- exam ined the typ e of p roced u re, sp ecific institu tional
nary angiograp hy may be ind icated . In general, ind ications com p lication rates, and other clinical factors in a sequential
for p reop erative coronary angiograp hy are sim ilar to those m anner follow ed by the ad d ition of the d ip yrid am ole-
id entified for the nonoperative setting (Table 10.5). thalliu m find ings. The ad d ition of d ip yrid am ole-thallium
Table 1 0 .5 Am er ica n College of Ca rd iology/Am er ica n H ea r t Associa t ion r ecom m en d a t ion s r ega r d in g
cor on a r y a n giogr a p hy befor e/a ft er n on -ca r d ia c su r ger y
Class I: Patients With Suspected or Known CAD (strongly recommended)
• Evidence for high risk of adverse outcome based on noninvasive test results
• Angina unresponsive to adequate medical therapy
• Unstable angina, particularly when facing intermediate-risk or high-risk noncardiac surgery
• Equivocal noninvasive test results in patients at high-clinical risk undergoing high-risk surgery
Class IIa (Weight of evidence/opinion is in favor of usefulness/efficacy)
• Multiple markers of intermediate clinical risk and planned vascular surgery (noninvasive testing should be considered first)
• Moderate to large ischemia on noninvasive testing but without high-risk features and lower LVEF
• Nondiagnostic noninvasive test results in patients of intermediate clinical risk undergoing high-risk noncardiac surgery
• Urgent noncardiac surgery while convalescing from acute MI
Class IIb (Usefulness/efficacy is less well established by evidence/opinion)
• Perioperative MI
• Medically stabilized class III or IVangina and planned low-risk or minor surgery
Class III (contraindicated)
• Low-risk noncardiac surgery with known CAD and no high-risk results on noninvasive testing
• Asymptomatic after coronary revascularization with excellent exercise capacity ( to 7 METs)
• Mild stable angina with good left ventricular function and no high-risk noninvasive test result.
• Noncandidate for coronary revascularization owing to concomitant medical illness, severe left ventricular dysfunction (e.g., LVEF less than 0.20), or
refusal to consider revascularization
Candidate for liver, lung, or renal transplant more than 40 years old as part of evaluation for transplantation, unless noninvasive testing reveals high risk
for adverse outcome.
CAD, coronary artery disease; LVEF, left ventricular ejection fraction; MI, myocardial infarction; MET, metabolic equivalents.
Adapted from Eagle KA, Berger PB, Calkins H, et al. ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery–executive summary: a report
of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascu-
lar Evaluation for Noncardiac Surgery). J Am Coll Cardiol 2002;39:542–553.
d ata reclassified 80% of the m od erate risk patients into metop rolol for the next 48 hou rs to m aintain a heart rate
low (3%) and high (19%) risk categories (p 0.0001) bu t less than 80 bp m . The nu m ber of ischem ic events (control,
provid ed no stratification for patients classified as low or 50; beta-blockers, 16) and total ischem ic tim e (control,
high risk accord ing to the clinical m od el. 709 m inu tes; beta-blocker, 236 m inu tes) w ere significantly
low er w ith esm olol com pared to those for the control
■ MODIFYING PREOPERATIVE RISK FACTORS grou p . In this stu d y p rop hylactic beta ad renergic blockad e
ad ministered after elective total knee arthrop lasty w as
CAD is resp onsible for the m ajority of life-threatening p eri- associated w ith a red u ced p revalence and d u ration of
op erative card iac com plications. Once recognized , sp ecific p ostop erative m yocard ial ischem ia d etected w ith H olter
therapy shou ld be institu ted to m inim ize the risk of periop - monitoring (26). The PeriOp erative ISchem ic Evaluation
erative m yocard ial ischemia, MI, or d eath. Several stu d ies (POISE) trial rand om ly assigned 8351 p atients w ith, or at
have ad d ressed the effect of anti-ischem ic m ed ical therap y risk of, atherosclerotic d isease w ho w ere u nd ergoing non-
on p eriop erative p rognosis (23). card iac surgery to receive extend ed -release m etoprolol suc-
cinate (n 4174) or p lacebo (n 4177) (27). In this large
■ Medical therapy stu d y, p eriop erative extend ed -release metop rolol red u ced
the risk of MI, card iac revascu larization, and clinically sig-
Beta-Blockers nificant atrial fibrillation 30 d ays after rand om ization com -
The effectiveness of beta-blockers in red u cing p eriop era- p ared w ith p lacebo; the d ru g also resu lted in a significant
tive card iac risk has been evalu ated in several stu d ies. The excess risk of d eath, stroke, and clinically significant
first rand om ized , p lacebo-controlled stu d y u sed atenolol hyp otension and brad ycard ia (27). The resu lts of this trial
in 200 h igh-risk p atien ts sch ed u led to u nd ergo n oncar- su ggest that the ad d ition of p eriop erative beta-blockers has
d iac su rgery inclu d ing vascu lar, orthopaed ic, intra-abd om - both p otential benefits and risks. Table 10.6 lists current
inal and n eu rosu rgical p roced u res (24). Atenolol w as guid eline recom m end ations for ap propriate u se of beta-
ad m inistered either intravenou sly or orally tw o d ays blockers in the p reop erative setting.
p reop eratively and continu ed for seven d ays p ostop era-
tively. The incid ence of p eriop erative ischem ia w as signif- Alpha 2-Adrenergic Agonists
icantly low er in the atenolol grou p than in the p lacebo The effect of 2-ad renergic agonists has also been stud ied
grou p (24,25). There w as no d ifference in the incid ence of in the p eriop erative p eriod . Several sm all, rand omized
p eriop erative MI or d eath from card iac cau ses, bu t the rate stu d ies com paring clonid ine w ith placebo failed to d em on-
of event-free su rvival at six m onths w as higher in the strate that clonid ine w as effective in red u cing the rates of
atenolol grou p . MI and d eath from card iac cau ses (16,28). Mivazerol, an
Pold erm ans et al. stud ied the perioperative u se of biso- intravenou s 2-ad renergic agonist ad m inistered by con-
p rolol in elective m ajor vascular surgery (20). Bisop rolol tinu ou s infu sion, w as comp ared w ith p lacebo in patients
w as started at least 7 d ays preoperatively, and the d ose w ith know n coronary d isease or risk factors w ho u nd er-
ad ju sted to achieve a resting heart rate of less than 60 beats w ent major vascu lar or orthop ed ic p roced u res. Mivazerol
p er m inu te and continu ed for 30 d ays p ostoperatively. The w as fou nd to have no overall effect on the rates of card iac
stu d y w as confined to p atients w ho had at least one card iac com p lications (29). H ow ever, in the p red efined su bgrou p
risk factor (a history of congestive heart failure, p rior MI, of p atients w ith know n CAD w ho u nd erw ent m ajor vascu -
d iabetes, angina p ectoris, heart failure, age 70 years, or lar su rgery, m ivazerol w as associated w ith a significantly
p oor functional statu s) and evid ence of ind ucible m yocar- low er incid ence of MI and d eath from card iac causes. This
d ial ischem ia on d obu tam ine echocard iography. Patients agent is u sed by som e institu tions in Eu rop e bu t has not
w ith extensive regional w all-m otion abnorm alities w ere been available in the United States.
exclu d ed . Bisop rolol w as associated w ith a 91% red u ction
in the p eriop erative risk of MI or d eath from card iac cau ses Calcium Channel Blockers and Nitrates
from 34% to 4% in this high-risk popu lation. Becau se of the There are no large rand om ized trials of either nitrates or
selection criteria used in this trial, the efficacy of bisop rolol calciu m channel antagonists in term s of red u cing p eriop er-
in the grou p at very highest risk, those in w hom coronary ative MI or card iac d eath. Therefore their u se in the periop -
revascu larization or m od ification w ould be consid ered or erative setting shou ld m irror that in the general card iology
for w hom the su rgical p roced u re m ight u ltim ately be can- p ractice. They are second line agents to beta-blockers for
celled , cannot be d eterm ined . The rate of events in the stan- the control of angina or stress ind u ced ischem ia. If a patient
d ard -care grou p of 34% suggests that all but the p atients at has requ ired either or both to control ischem ia, then they
highest risk w ere enrolled in the trial. Urban et al. evalu - should be continued perioperatively.
ated the role of prophylactic beta-blockers in p atients
u nd ergoing elective total knee arthrop lasty (26). One hu n- Statins
d red and seven p atients w ere p reop eratively rand om ized H MG CoA red u ctase inhibitors [statins] have been show n
into tw o grou p s, control and beta-blockers, w ho received to red u ce ischem ic events, stroke, and card iac d eath
p ostoperative esm olol infu sions on the d ay of su rgery and in p atients w ith established atherosclerosis. In patients
Table 1 0 .6 Recom m en d a t ion s for bet a -block er m ed ica l t h era py

Class I
1. Beta blockers should be continued in patients undergoing surgery who are receiving beta blockers to treat angina, symptomatic arrhythmias, hyper-
tension.
2. Beta blockers should be given to patients undergoing vascular surgery who are at high cardiac risk owing to the finding of ischemia on preoperative
testing
Class IIa
1. Beta blockers are probably recommended for patients undergoing vascular surgery in whom preoperative assessment identifies coronary heart dis-
ease.
2. Beta blockers are probably recommended for patients in whom preoperative assessment for vascular surgery identifies high cardiac risk, as defined
by the presence of more than one clinical risk factor.
3. Beta blockers are probably recommended for patients in whom preoperative assessment identifies coronary heart disease or high cardiac risk, as de-
fined by the presence of more than one clinical risk factor, who are undergoing intermediate-risk or vascular surgery.
Class IIb
1. The usefulness of beta blockers is uncertain for patients who are undergoing either intermediate-risk procedures or vascular surgery, in whom preop-
erative assessment identifies a single clinical risk factor.
2. The usefulness of beta blockers is uncertain in patients undergoing vascular surgery with no clinical risk factors who are not currently taking beta
blockers.
Class III
1. Beta blockers should not be given to patients undergoing surgery who have absolute contraindications to beta blockade.
u nd ergoing vascu lar su rgery, several recent reports su g- gery (33–35). The ind ications for PCI w ere not w ell
gest statins m ay red uce perioperative coronary events (30). d escribed in the stu d ies bu t m ost likely inclu d ed the need
Since stains are know n to red u ce atherosclerotic plaque for- to relieve sym p tom atic angina or red u ce the p eriop erative
m ation and grow th and p otentially stabilize p laqu es that risk of ischem ia id entified by noninvasive testing. All three
have been p reexistent, it is not entirely surprising that they stu d ies had a low incid ence of card iac com p lications after
cou ld red u ce the risk of coronary p laqu e ru p tu re and noncard iac su rgery, bu t no com p arison grou ps w ere
throm bosis d u ring or after the stresses of vascu lar su rgery. inclu d ed .
H ind ler et al. (31) cond u cted a m eta-analysis to evalu ate One stu d y used an ad m inistrative d atabase of patients
the overall effect of preoperative statin therapy and w ho w ere u nd ergoing noncard iac su rgery in the State of
reported a 44% red u ction in m ortality. Le Manach et al. Washington. As com p ared w ith p atients w ho d id not
d em onstrated that p ostop erative statin w ithd raw al (m ore u nd ergo PCI p reop eratively, those w ho d id u nd ergo the
than four d ays) w as an ind epend ent pred ictor of postoper- p roced u re had a low er incid ence of p eriop erative card iac
ative m yonecrosis (32). Further stu d ies are need ed to d eter- com p lications (36). The benefit of revascu larization w as
m ine how long the statins m u st be given before a m ost ap p aren t in th e grou p that u n d erw ent PCI at least
p eriop erative benefit can be realized . Based on cu rrent 90 d ays before noncard iac su rgery. In contrast, w hen revas-
evid ence, p atients taking statins, and sched u led for noncu larization w as p erform ed w ithin 90 d ays before noncar-
card iac su rgery, should continue statins. For p atients d iac su rgery, PCI w as not associated w ith an im proved
u nd ergoing vascu lar su rgery w ith or w ithout clinical risk ou tcom e. The Coronary Artery Revascu larization Prophy-
factors, statin u se is reasonable and m ay be consid ered in laxis (CARP) trial prospectively assessed the long-term
p atients w ith at least one clinical risk factor w ho are u nd er- benefit of p reop erative coronary-artery revascu larization
going interm ed iate-risk proced u res (3). am ong p atients w ith stable CAD w ho are sched u led for
elective vascu lar su rgery. In this trial, coronary-artery
■ Revascularization revascularization before elective vascular surgery d id not
significantly alter the long-term ou tcom e (37). These find -
Percutaneous Revascularization ings w ou ld su ggest that PCI shou ld not be u sed solely as a
Percu taneous coronary intervention (PCI) utilizing p rim a- m eans of red u cing p eriop erative risk.
rily balloon angiop lasty has been evaluated in three stu d ies Coronary stents are now u sed in m ore than 80% of PCI,
involving p atients w ho w ere u nd ergoing noncard iac su r- and u se of stents d u ring PCI p resents u niqu e challenges
becau se of the risk of coronary throm bosis and bleed ing therap y for su bsequ ent coronary sym p tom s or signs, is
d u ring the initial recovery phase. In a cohort of 40 p atients associated w ith a low rate of card iac events after noncar-
w ho received stents w ithin 30 d ays of noncard iac su rgery, d iac su rgery (42). The CARP trial rand om ly assigned 510
all eight d eaths and seven MIs, as w ell as eight of 11 bleed - p atients w ith significant coronary artery stenosis to either
ing ep isod es, occu rred in p atients w ho had u nd ergone coronary artery revascularization before su rgery or no
surgery w ithin 14 d ays of stent placem ent (38). The com p li- revascu larization before su rgery. Rou tine coronary revas-
cations ap p eared to be related to seriou s bleed ing resu lting cu larization in patients w ith stable card iac sym ptom s
from p ostp roced u ral anticoagu lant therap y or to coronary before elective vascu lar su rgery d id not significantly alter
throm bosis in th ose w h o d id n ot receive fou r fu ll w eeks the long-term ou tcom e or short-term risk of d eath or MI in
of antithrom botic therapy after stenting. In general, one this stu d y (37). The DECREASE-V p ilot stu d y id entified a
shou ld w ait at least 14 d ays after balloon angioplasty, 30–45 high-risk cohort of p atients sched u led for vascu lar su rgery
d ays after bare m etal coronary stenting and 365 d ays after w ho w ere rand om ized to best m ed ical therap y and revas-
d ru g elu ting stents to perform noncard iac surgery in ord er cu larization or best m ed ical therapy alone before vascu lar
to allow com plete end othelization and a full course of d u al su rgery. There w as no d ifference in the com bined outcom es
antip latelet therapy to be given (3,39). Drug eluting stents of d eath or MI at 30 d ays or 1 year betw een the revascular-
should not be im planted in ind ivid uals w ho w ill u nd ergo ization and m ed ical therap y grou p s (43). Based on recent
noncard iac su rgery w ithin a year of im p lantation. stu d ies, rou tine p rop hylactic coronary revascularization
w ith either PCI or CABG shou ld not be p erform ed in
Coronary-Artery Bypass Grafting p atients w ith stable CAD before noncard iac su rgery.
Coronary artery byp ass grafting (CABG) has also been rec-
om m end ed to red u ce the incid ence of perioperative car-
d iac com p lications in highly selected patients. Evid ence of
■ IDENTIFICATION OF POSTOPERATIVE
a p otential p rotective effect of preoperative coronary-artery
COMPLICATIONS
bypass grafting com es from follow -u p stu d ies of rand om - Perioperative MI can be d ocu m ented by assessing clinical
ized trials and / or registries com p aring m ed ical and su rgi- sym p tom s, serial ECGs, and card iac-sp ecific biom arkers.
cal therap y for coronary artery d isease. The largest stu d y On the basis of cu rrent evid ence, in p atients w ithout d ocu -
to d ate inclu d ed 3,368 noncard iac operations p erform ed m ented CAD, su rveillance shou ld be restricted to those
w ithin a 10-year p eriod am ong p atients assigned to m ed - p atients w ho d evelop perioperative signs of card iovascu lar
ical therap y or coronary-artery byp ass grafting in the d ysfu nction. Postop erative trop onin m easu rem ent is rec-
Coronary Artery Su rgery Stud y (40). Prior su ccessfu l coro- om m end ed in p atients w ith ECG changes or chest pain
nary-artery byp ass grafting had a card io-p rotective effect typ ical of acu te coron ary synd rom e (3). Periop erative
am ong p atients w ho u nd erw ent high-risk noncard iac su r- su rveillance for acu te coronary synd rom es w ith rou tine
gery (abd om inal, thoracic, vascu lar, or orthop aed ic su r- ECG and card iac seru m biom arkers is u nnecessary in clin-
gery) (40). The perioperative m ortality rate w as nearly ically low -risk p atients u nd ergoing low -risk op erative
50 p ercent low er in the group of patients w ho had u nd er- p roced u res.
gone coronary-artery byp ass grafting than in those w ho
received m ed ical therapy (3.3% vs. 1.7%, p 0.05). There
w as no d ifference in the ou tcom e of patients u nd ergoing
■ MANAGEMENT OF COMPLICATIONS
low -risk p roced u res su ch as breast and u rologic su rgery. Desp ite op tim al p eriop erative m anagem ent, som e p atients
Fleisher et al. u sed Med icare claims d ata to assess 30-d ay w ill exp erience p eriop erative MI, w hich is associated w ith
and 1-year m ortality after noncard iac su rgery accord ing to 40%–70% m ortality. The reason for the high m ortality is
the u se of card iac testing and coronary interventions su ch m u ltifactorial and largely related to su bstantial com orbid -
as CABG and PCI w ithin the year before noncard iac su r- ity in su ch p atients. Patients w ho d evelop ST-elevation MI
gery (41). Preop erative revascu larization significantly should be consid ered for u rgent coronary reperfu sion
red u ced the 1-year m ortality rate for patients u nd ergoing w hereas patients w ith non ST-elevation MI shou ld u nd ergo
aortic su rgery bu t had no effect on the m ortality rate for risk stratification after initial stabilization w ith intensive
those u nd ergoing infraingu inal surgeries. Finally, an analy- m ed ical therap y. Ind ivid u als w ho d evelop heart failu re
sis of the Bypass Angioplasty Revascu larization Investiga- after su rgery shou ld be evalu ated for the etiology of heart
tion (BARI) evalu ated the incid ence of p ostoperative failu re and treated based on the p recip itating or u nd erlying
card iac com p lications after noncard iac su rgery am ong cau se. Im m ed iate coronary angiop lasty is feasible and ben-
p atients w ith m u ltivessel coronary d isease w ho w ere ran- eficial in p atients w ith ST-elevation MI. H ow ever, time to
d om ly assigned to u nd ergo PCI or CABG for severe angina reperfu sion is a critical d eterm inant of ou tcom e in acu te
(42). At an average of 29 m onths after coronary revascu lar- MI, and any hop e of benefiting p atients w ho have a periop-
ization, both grou ps had sim ilar, low rates of postop erative erative acu te MI d u e to an acu te coronary occlu sion
MI or d eath from card iac cau ses (1.6% in each grou p ). requ ires that revascu larization be rap id ly p erform ed (i.e.,
These d ata suggest that prior su ccessful coronary revascu - w ithin 12 hou rs of sym p tom onset). Since fibrinolytics are
larization, w hen accom panied by careful follow -u p and u su ally contraind icated in this circu m stance, and d u al
antiplatelet therap y m ay not be id eal either, balloon angio- 4. Eagle KA, Berger PB, Calkins H , et al. ACC/ AH A gu id eline u p d ate
for p erioperative card iovascular evaluation for noncard iac surgery–
p lasty w ithou t stenting is often the best strategy. executive su m m ary: a report of the Am erican College of Card iology/
Althou gh im m ed iate rep erfu sion therap y is an im - Am erican H eart Association Task Force on Practice Gu id elines (Com -
p ortant therap y in acu te ST-segm ent-elevation MI, the m ittee to Upd ate the 1996 Gu id elines on Periop erative Card iovascu lar
Evaluation for N oncard iac Su rgery). J Am Coll Cardiol 2002;39:542–553.
em p hasis on rep erfu sion therap y shou ld not d etract from 5. Mu kherjee D, Eagle KA. A com m on sense ap p roach to p eriop erative
p harm acological therapy, w hich is also very imp ortant and evalu ation. Am Fam Physician 2002;66:1824–1826.
has been show n to red u ce ad verse events in su ch p atients, 6. Mu kherjee D, Eagle KA. Card iac risk in noncard iac su rgery. Minerva
Cardioangiol 2002;50:607–619.
as w ell as in p atients w ith non-ST-elevation acute coronary 7. Mu kherjee D, Eagle KA. Periop erative card iac assessm ent for noncar-
synd rom es. Therap y w ith aspirin, a beta blocker, and often d iac su rgery: eight step s to the best p ossible ou tcom e. Circulation 2003;
an angiotensin-converting enzym e inhibitor, particu larly 107:2771–2774.
8. Logeais Y, Langanay T, Rou ssin R, et al. Su rgery for aortic stenosis in
for p atients w ith low ejection fractions or anterior infarc- eld erly p atients. A stu d y of su rgical risk and p red ictive factors. Circula-
tions, shou ld be ad m inistered w here p ossible. Patients w ho tion 1994;90:2891–2898.
sustain acute myocard ial injury in the p erioperative or 9. Raym er K, Yang H . Patients w ith aortic stenosis: card iac com p lications
in non-card iac su rgery. Can J Anaesth 1998;45(9):855–859.
p ostoperative period shou ld receive careful m ed ical evalu- 10. Torsher LC, Shub C, Rettke SR, et al. Risk of p atients w ith severe aortic
ation for resid u al ischem ia and overall LV function. In all stenosis u nd ergoing noncard iac su rgery. Am J Cardiol 1998;81(4):
cases, the ap p rop riate evaluation and m anagem ent of com - 448–452.
11. DePu ey EG, Guertler-Kraw czynska E, Robbins WL. Thalliu m -201
p lications and coronary risk factors su ch as angina, heart SPECT in coronary artery d isease patients w ith left bund le branch
failu re, hyp ertension, hyperlip id em ia, cigarette sm oking, block. Q J Nucl Med 1988;29(9):1479–1485.
d iabetes (hyp erglycem ia), and other card iac abnorm alities 12. Larcos G, Gibbons RJ, Brow n ML. Diagnostic accu racy of exercise
thallium -201 single-photon em ission com p u ted tom ograp hy in
should com m ence before hospital d ischarge. Most p ost-MI p atients w ith left bund le branch block. Am J Cardiol 1991;68(8):756–760.
p atients should also receive a statin at d ischarge. 13. Rockett JF, Wood WC, Moinu d d in M, et al. Intravenou s d ip yrid am ole
thallium -201 SPECT im aging in p atients w ith left bu nd le branch block.
Clin Nucl Med 1990;15(6):401–407.
■ CONCLUSIONS
14. O’Keefe JH Jr, Batem an TM, Barnhart CS. Ad enosine thalliu m -201 is
su perior to exercise thalliu m -201 for d etecting coronary artery d isease
in patients w ith left bu nd le branch block. J Am Coll Cardiol 1993;21(6):
Ap p rop riate p reop erative evalu ation and therap y m ay 1332–1338.
significantly im prove periproced ural and long-term out- 15. H irzel H O, Senn M, N u esch K, et al. Thalliu m -201 scintigrap hy in com -
p lete left bund le branch block. Am J Cardiol 1984;53(6):764–769.
com es. Su ccessfu l m anagem ent of high-risk p atients 16. Ellis JE, Drijvers G, Ped low S, et al. Prem ed ication w ith oral and trans-
requ ires an integrated “team ” app roach betw een su rgeons, d erm al clonid ine p rovid es safe and efficaciou s p ostop erative sym p a-
anesthesiologists, card iologists, and generalists. In general, tholysis. Anesth Analg 1994;79(6):1133–1140.
17. Shaw LJ, Eagle KA, Gersh BJ, et al. Meta-analysis of intravenou s
ind ications for fu rther card iac testing and revascu lariza- d ip yrid am ole-thalliu m -201 im aging (1985 to 1994) and d obu tam ine
tion are the sam e as in the nonoperative setting. Beta- echocard iograp hy (1991 to 1994) for risk stratification before vascu lar
blocker therapy should be consid ered in appropriate su rgery. J Am Coll Cardiol 1996;27(4):787–798.
18. Bou cher CA, Brew ster DC, Darling RC, et al. Determ ination of card iac
p atients at high risk for coronary events w ith the u nd er- risk by d ip yrid am ole-thalliu m im aging before perip heral vascu lar su r-
stand ing that these agents have both benefits and risks. For gery. N Engl J Med 1985;312(7):389–394.
m any p atients, evalu ation prior to noncard iac su rgery m ay 19. Lepp o J, Plaja J, Gionet M, et al. N oninvasive evalu ation of card iac risk
before elective vascu lar su rgery. J Am Coll Cardiol 1987;9(2):269–276.
be the first com p rehensive assessm ent of their short-term 20. Pold erm ans D, Boersm a E, Bax JJ, et al. The effect of bisop rolol on p eri-
and long-term card iac risk and p rovid es an opportu nity to operative m ortality and m yocard ial infarction in high-risk p atients
not only d ecrease their im m ed iate p erip roced u ral risk bu t u nd ergoing vascu lar su rgery. Du tch Echocard iograp hic Card iac Risk
Evaluation App lying Stress Echocard iograp hy Stu d y Grou p . N Engl J
also to im p rove their long-term ou tcom es w ith approp riate Med 1999;341(24):1789–1794.
evid ence based therap ies. Early id entification and ap p ro- 21. Eagle KA, Coley CM, N ew ell JB, et al. Com bining clinical and thalliu m
p riate m anagem ent of post-operative com plications is d ata op tim izes p reop erative assessm ent of card iac risk before m ajor
vascular su rgery. Ann Intern Med 1989;110(11):859–866.
im p ortant and may p revent fatality. 22. L’Italien GJ, Pau l SD, H end el RC, et al. Develop m ent and valid ation of
a Bayesian m od el for p eriop erative card iac risk assessm ent in a cohort
of 1,081 vascu lar su rgical cand id ates. J Am Coll Cardiol 1996;27(4):779–
■ REFERENCES 786.
23. Pasternack PF, Grossi EA, Bau m ann FG, et al. Beta blockad e to d ecrease
1. N ational Center for H ealth Statistics. Vital statistics of the United States: silent m yocard ial ischem ia d u ring p erip heral vascu lar su rgery. Am J
2003. Washington, DC: N CH S U.S. Pu blic H ealth Services; 2003, 2004. Surg 1989;158(2):113–116.
2. Mangano DT. Periop erative card iac m orbid ity. Anesthesiology 1990;72: 24. Mangano DT, Layu g EL, Wallace A, et al. Effect of atenolol on m ortality
153–184. and card iovascu lar m orbid ity after noncard iac su rgery. Mu lticenter
3. Fleisher LA, Beckm an JA, Brow n KA, et al. ACC/ AHA 2007 Gu id elines Stu d y of Perioperative Ischem ia Research Grou p . N Engl J Med 1996;
on perioperative card iovascular evaluation and care for noncard iac 335(23):1713–1720.
su rgery: execu tive sum m ary: a rep ort of the Am erican College of 25. Wallace A, Layug B, Tateo I, et al. Prop hylactic atenolol red u ces p ost-
Card iology/ American H eart Association Task Force on Practice Guid e- op erative m yocard ial ischem ia. McSPI Research Grou p . Anesthesiology
lines (Writing Com m ittee to Revise the 2002 Gu id elines on Periopera- 1998;88(1):7–17.
tive Card iovascu lar Evalu ation for Noncard iac Surgery): d evelop ed in 26. Urban MK, Markow itz SM, Gord on MA, et al. Postop erative p rop hy-
collaboration with the American Society of Echocardiography, American lactic ad m inistration of beta-ad renergic blockers in p atients at risk for
Society of N u clear Card iology, H eart Rhythm Society, Society of Card io- m yocard ial ischem ia. Anesth Analg 2000;90(6):1257–1261.
vascu lar Anesthesiologists, Society for Card iovascu lar Angiography 27. Devereau x PJ, Yang H , Yu su f S, et al. Effects of extend ed -release m eto-
and Interventions, Society for Vascular Med icine and Biology, and Soci- prolol su ccinate in patients u nd ergoing non-card iac su rgery (POISE
ety for Vascu lar Su rgery. Circulation 2007;116:1971–1996. trial): a rand om ised controlled trial. Lancet 2008;371(9627):1839–1847.
28. Stu hm eier KD, Mainzer B, Cierp ka J, et al. Sm all, oral d ose of clonid ine 36. Posner KL, Van N orm an GA, Chan V. Ad verse card iac ou tcom es after
red uces the incid ence of intraoperative m yocard ial ischem ia in patients noncard iac su rgery in patients w ith p rior percutaneous translu m inal
having vascular su rgery. Anesthesiology 1996;85(4):706–712. coronary angiop lasty. Anesth Analg 1999;89(3):553–560.
29. Oliver MF, Gold m an L, Ju lian DG, et al. Effect of m ivazerol on p eriop- 37. McFalls EO, Ward H B, Moritz TE, et al. Coronary-artery revascu lariza-
erative card iac com plications d u ring non-card iac su rgery in patients tion before elective m ajor vascu lar su rgery. N Engl J Med 2004;351(27):
w ith coronary heart d isease: the Europ ean Mivazerol Trial (EMIT). 2795–2804.
Anesthesiology 1999;91(4):951–961. 38. Kalu za GL, Josep h J, Lee JR, et al. Catastrop hic ou tcom es of noncard iac
30. Pold erm ans D, Bax JJ, Kertai MD, et al. Statins are associated w ith a su rgery soon after coronary stenting. J Am Coll Cardiol 2000;35(5):
red u ced incid ence of perioperative m ortality in patients u nd ergoing 1288–1294.
m ajor noncard iac vascu lar su rgery. Circulation 2003;107(14):1848–1851. 39. Wilson SH , Fasseas P, Orford JL, et al. Clinical ou tcom e of p atients
31. H ind ler K, Shaw AD, Sam u els J, et al. Im p roved p ostoperative ou t- u nd ergoing non-card iac su rgery in the tw o m onths follow ing coronary
com es associated w ith p reop erative statin therap y. Anesthesiology stenting. J Am Coll Cardiol 2003;42(2):234–240.
2006;105(6):1260–1272 and 1289–1290. 40. Eagle KA, Rihal CS, Mickel MC, et al. Cardiac risk of noncardiac surgery:
32. Le Manach Y, God et G, Coriat P, et al. The im p act of p ostop erative influence of coronary disease and type of surgery in 3368 operations.
d iscontinu ation or continu ation of chronic statin therap y on card iac CASS Investigators and University of Michigan Heart Care Program .
ou tcom e after m ajor vascu lar su rgery. Anesth Analg 2007;104(6): Coronary Artery Surgery Stud y. Circulation 1997;96(6):1882–1887.
1326–1333. 41. Fleisher LA, Eagle KA, Shaffer T, et al. Perioperative and long-term mor-
33. Allen JR, H elling TS, H artzler GO. Op erative p roced u res not involving tality rates after major vascular surgery: the relationship to preoperative
the heart after p ercu taneou s translu m inal coronary angiop lasty. Surg testing in the m ed icare population. Anesth Analg 1999;89(4):849–855.
Gynecol Obstet 1991;173(4):285–288. 42. H assan SA, H latky MA, Boothroyd DB, et al. Ou tcom es of noncard iac
34. Elm ore JR, H allett JW Jr, Gibbons RJ, et al. Myocard ial revascu lariza- su rgery after coronary byp ass su rgery or coronary angiop lasty in the
tion before abd om inal aortic aneu rysm orrhap hy: effect of coronary Bypass Angiop lasty Revascu larization Investigation (BARI). Am J Med
angioplasty. Mayo Clin Proc 1993;68(7):637–641. 2001;110(4):260–266.
35. Gottlieb A, Banou b M, Sp ru ng J, et al. Periop erative card iovascu lar 43. Pold erm ans D, Schou ten O, Vid akovic R, et al. A clinical rand om ized
m orbid ity in patients w ith coronary artery d isease und ergoing vascu- trial to evalu ate the safety of a noninvasive ap p roach in high-risk
lar surgery after p ercu taneou s translu m inal coronary angiop lasty. p atients u nd ergoing m ajor vascu lar su rgery: the DECREASE-V Pilot
J Cardiothorac Vasc Anesth 1998;12(5):501–506. Stu d y. J Am Coll Cardiol 2007;49(17):1763–1769.
CHAPTER
11
Assessment of Noncardiac
Perioperative Risk
Pauline K. Park
■ INTRODUCTION mizing” any of these single param eters is not know n and
som e of the variables, su ch as age, are fixed . Recent evalu a-
Determination of perioperative risk is a critical step in pre- tion of the ACS-N SQIP d atabase fou nd that w hile rates of
venting complications in surgery. Surgical patients often pres- ind ivid u al com plications d id not vary significantly am ong
ent with multisystem disease separate from the process hosp itals w ith d iffering m ortality rates, m ortality in
requiring operation; the surgeon must weigh not only the risk p atients w ith m ajor com p lications w as alm ost tw ice as
attributable to the surgical procedure, but also the additional high in hospitals w ith very high overall m ortality as in
contributions of underlying medical comorbidities. Variations those w ith very low overall m ortality (21.4% vs. 12.5%,
in preoperative status have been associated with operative P 0.001)(6). This su ggests that the qu ality of p erioperative
outcomes (1), hospital length of stay (2), and hospital costs (3). care provid ed once com plications occu r m ay be as im por-
Risk assessm ent in general su rgery has ad vanced tant as the efforts to p revent them . N evertheless, the ability
greatly over the past tw o d ecad es. The most comprehensive to system atically id entify p atients at higher risk, analyze
effort to d ate has been the N ational Surgical Quality variations in p ractice, and reliably change hosp ital level
Im p rovem ent Program (N SQIP) (1). Since 1991, the Depart- p rocess has resu lted in im p rovem ent in overall ou tcom es.
ment of Veterans Affairs (VA) has systematically collected Risk assessment aids the surgeon in appropriately advis-
and analyzed risk-ad justed surgical d ata in VA hospitals. ing patient expectations and in developing strategies to
Trained nurse review ers at each VA site regu larly abstract potentially reduce postoperative complications (7). As the
d em ographic inform ation, baseline physiologic status, occurrence of postoperative complications remains one of the
med ical comorbid ity, laboratory values, and operative char- strongest predictors of long term outcomes after major surgery
acteristics in su rgical patients. By m easuring and analyzing (8,9), the time spent evaluating and optimizing the patient pre-
patient level d ata, the VA has been able to implement operative status can directly facilitate the best outcomes.
changes based on observed hospital variations in outcome.
The p rogram is cred ited w ith increasing patient satisfaction
and red ucing complications, 30-d ay mortality and hospital ■ ELECTIVE SURGERY
length of stay in a broad range of surgical patients (4). Preop erative evalu ation for elective su rgery is m ost com -
The N SQIP p rovid es an im portant, valid ated tool for monly p erform ed in the ou tp atient setting. Centralized
risk assessm ent. The program has been ad opted by the centers facilitate registration, anesthesia evalu ation, and
Am erican College of Su rgeons (ACS-N SQIP) and this ini- p reop erative teaching, resulting in decreased costs as well as
tiative su pplem ents initial N SQIP d ata d erived from the improved laboratory utilization and rates of cancellation on
p rim arily old er, m ale pop ulation seen in the VA system . the date of surgery (10–12). Patient education is critical in
Data collection w as successfu lly m irrored in the private- ensuring that patients understand expectations of care to be
sector hosp ital environm ent in a valid ation cohort of 14 delivered. Performing this in the preoperative setting not only
acad em ic m ed ical centers (5). The m ost pred ictive p reop er- ensures cooperation with postoperative interventions but also
ative risk factors for m ortality and m orbid ity in private sec- improves patient satisfaction (13). Ideally, appointments
tor, noncard iac su rgery patients are su mm arized in Tables should be scheduled well ahead of the actual date of surgery,
11.1 and 11.2. Sim ilar to the VA experience, im plem entation to allow for complete assessment and to allow patients time to
of the ACS-N SQIP d em onstrated red u ctions in postop era- assimilate the information and instructions given to them.
tive m orbid ity, su rgical site infections, renal com plications, A stand ard m ed ical history is p erform ed to id entify
and 30-d ay p ostop erative m orbid ity (5). med ication allergies, cu rrent m ed ications (inclu d ing pre-
The m ajority of p reop erative risk variables id entified by scrip tion, over-the-cou nter, and alternative m ed ications),
N SQIP and ACS-N SQIP relate to und erlying system ic d is- p rior or fam ilial d isord ers w ith anesthetics, p rior history
ease and acu ity of p resenting illness. The im pact of “op ti- of bleed ing d isord er and p rior m ed ical history. A com -
p lete p hysical exam ination is p erform ed to id entify other
Pauline K. Park: University of Michigan, Ann Arbor, MI concu rrent find ings sep arate from the p lanned su rgical
48109 p roced u re, d eterm ine nu tritional statu s, and ascertain the
78
Chapter 11 • Assessment of Noncardiac Perioperative Risk 79
Table 1 1 .1 Logistic regression m odels for Table 1 1 .2 Logistic r egr ession m odels for
pr edict ion of 30-day opera t ive prediction of 30-day operative
m ort a lity u sin g p reop era tive va r ia bles m orbidity u sin g preoperative variables
Variable Odds Ratio Variable Odds Ratio
ASA class 4/5 vs. 1/2 8.1 ASA 4/5 vs. 1/2 2.1
ASA 3 vs. 1/2 3.5 ASA 3 vs. 1/2 1.6
Serum albumin (per gram) 0.62 Albumin (per gram) 0.73
Emergency operation 2.6 Work RVU (per unit) 1.05
Age (per year) 1 Emergency operation 1.7
Platelet count 150,000 1.9 Dyspnea at rest vs. none 1.7
Disseminated cancer 2.9 Dyspnea with minimal exertion vs. none 1.2
Dyspnea at rest vs. none 1.6 Wound infection 1.6
Dyspnea with minimal exertion vs. none 1.3 Patient on ventilator prior to surgery 1.9
DNR 3.9 Bleeding disorder 1.5
BUN 40 mg/dL 1.3 WBC 11,000/mL3 1.2
Work RVU (per unit) 1.02 Age (per year) 1.01
Derived from private sector hospitals, n 54,450 patients. Derived from private sector hospitals, n 54,450 patients.
ASA, American Society of Anesthesiologist’s Patient Severity Score; BUN, blood ASA, American Society of Anesthesiologist’s Patient Severity Score; BUN, blood
urea nitrogen; DNR, do not resuscitate; RVU, relative value unit; COPD, chronic urea nitrogen; DNR, do not resuscitate; RVU, relative value unit; COPD, chronic
obstructive pulmonary disease; WBC, white blood cell count k/cmm. obstructive pulmonary disease; WBC, white blood cell count k/cmm.
From Khuri SF, Henderson WG, Daley J, et al. Successful implementation of the From Khuri SF, Henderson WG, Daley J, et al. Successful implementation of the
Department of Veterans Affairs’ National Surgical Quality Improvement Program in the Department of Veterans Affairs’ National Surgical Quality Improvement Program in the
private sector: the Patient Safety in Surgery study. Ann Surg 2008;248(2):329–336. private sector: the Patient Safety in Surgery study. Ann Surg 2008;248(2):329–336.
presence of acu te infection. Form al evalu ation by anesthe- gery, but certain medications should be discontinued prior to
siology is p erform ed for su itability for regional and general surgery, with consideration given to risk of continuation ver-
anesthesia (see Chapter 12). sus the risk of intra-operative complications (Table 11.3).
A significant number of patients take prescription medica- H erbal m ed ications and su p p lem ents are increasingly
tions which require individual management perioperatively p op u lar (15). Sp ecific inqu iry as to their u se shou ld be
(14). The majority can be administered until the day of sur- inclu d ed in the p reop erative history, as the p atient m ay not
Table 1 1 .3 Com m on p r escr ip t ion m ed ica t ion s t h a t m ay r eq u ir e sp ecia l

p er iop er a t ive m a n a gem en t
Steroids May require perioperative stress dose steroids
Metformin Risk of lactic acidosis, withhold at least 2 days prior to surgery
Insulin Adjust dose prior to surgery
Anticoagulants May require bridge therapy with unfractionated or LMW heparin
Aspirin, thienopyridines (clopidogrel, Ticlid) Withhold seven days prior to surgery with increased bleeding
or dipyridamole (Persantine) risk
NSAIDs Withhold prior to surgery with risk of renal complications
Angiotensin converting enzyme inhibitors, Renal risk
angiotensin receptor blockers
Potassium sparing diuretics Renal risk, potential for hyperkalemia
Lithium Potential prolongation of neuromuscular blockade, sedative
action, cardiac arrhythmia, withhold at least 1 day prior to surgery
Monoamine oxidase inhibitors Anesthetic interactions
Butyrophenone Pain management
Oral contraceptives, conjugated estrogen Increase hypercoagulable state, consider holding 4 weeks prior to
surgery, DVT prophylaxis
LMW, low molecular weight; NSAIDs, nonsteroidal anti-inflammatory drugs; DVT, deep venous thrombosis.
Table 1 1 .4 Pot en t ia l in t er a ct ion s for som e com m on h er ba l m ed icin es

Preoperative
Common Name of Herb Potential Interactions Recommendations
Echinacea Allergic reactions; decreased effectiveness of immunosuppressants; potential No data
for immunosuppression with long-term use, potential hepatotoxicity
Ephedra Risk for myocardial ischemia and stroke from tachycardia and hypertension; Discontinue at least 24 hr before
ventricular arrhythmias with halothane; long-term use depletes endogenous surgery
catecholamines and may cause intra-operative hemodynamic instability;
life-threatening interaction with monoamine oxidase inhibitors
Dong Quai Potential to increase risk for bleeding, especially when combined with other Consider discontinuation 7 days
medications that inhibit platelet aggregation before surgery (36 hours for ginkgo)
Vitamin E
Evening Primrose Oil
Fish Oil
Feverfew
Garlic
Ginkgo
Ginger
Ginseng
Guarana
Goldenseal
Ginseng Hypoglycemia; potential to increase risk for bleeding; potential to decrease Discontinue at least 7 days
anticoagulative effect of warfarin before surgery
Kava Potential to increase sedative effect of anesthetics; potential for addiction, Discontinue at least 24 hr before
tolerance, and withdrawal after abstinence unstudied surgery
St. John’s wort Induction of cytochrome P-450 enzymes, with effect on cyclosporine, warfarin, Discontinue at least 5 days
steroids, protease inhibitors, and possibly benzodiazepines, calcium channel before surgery
blockers, and many other drugs; decreased serum digoxin levels
Valerian Potential to increase sedative effect of anesthetics; benzodiazepine-like acute No data
withdrawal; potential to increase anesthetic requirements with long-term use
Adapted from Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA2001;286(2):208–216 and Halaszynski TM, Juda R, Silverman DG. Optimizing
postoperative outcomes with efficient preoperative assessment and management. Crit Care Med 2004;32(4, Suppl):S76–S86.
consid er these to be “m ed ications” or they m ay be reluc- qu ality partnership com m itted to im proving safety of sur-
tant to rep ort u sing nontrad itional therapy (16). The qu al- gical care by significantly red u cing surgical com plications.
ity of p rep arations, content of actual ingred ients, and The national goal of the organization is to red u ce p reventa-
consistency are not alw ays know n and an exact m echanism ble su rgical com p lications by 25% by 2010 (21). Practice rec-
of action cannot alw ays be cited . N evertheless, m u ltip le om m end ations are focu sed on fou r areas: su rgical site
d ru g-herbal preparation interactions have been rep orted , infection, venou s throm boem bolism p rop hylaxis, card iac
includ ing effects on platelet aggregation, p450 cytochrom e su rgery, and ventilator associated p neu m onia. SCIP core
fu nction, and d ru g m etabolism (15) (Table 11.4) d atasets have broad ad ministrative su p p ort. H osp ital d ata
The ad d ed valu e and cost-effectiveness of rou tine p resu bm ission and analysis is cu rrently requ ired for Joint
op erative laboratory and chest x-ray testing has been d is- Com m ission accred itation, national and state regulatory
puted and the p ractice has been largely d iscou nted (10,17). com p liance as w ell as insu rance p lan initiatives. Process
Evid ence su ggests that results are often norm al, and even and ou tcom e m easu res in infection and venou s throm -
w hen abnorm al, they d o not alter the cou rse of treatm ent boem bolism p rop hylaxis are d ep icted in Table 11.6.
(18,19). Recom m end ations for p reoperative testing shou ld
be based on p atient history and physiologic status and p er-
form ed selectively (20) (Table 11.5).
■ EMERGENCY SURGERY
Prophylaxis for surgical site infection and venous Em ergency p roced u res are often p erform ed in acu te situ -
throm boem bolism shou ld also be ord ered ap p rop riately. ations w ith lim ited op p ortu nities to op tim ize p reop era-
The Su rgical Care Im p rovem ent Project (SCIP) is a national tive statu s. The need for em ergent intervention has been
Table 1 1 .5 Su ggest ion s for a d u lt p r eop era t ive t est in g

BASIC ADDITIVE SURGICAL AND MEDICAL FACTORS
MINOR SURG.
IN HEALTHY CLINICALLY SIGNIFICANT AND CHANGING
PATIENT SURGICAL PROCEDURES DISORDERS AND/OR MEDICATIONS
(w/in 90 days) (within 90 days) (white w/in 90 days; grey given test for given disorder likely should be w/in 30 days)
Cancer (?metastatic)
Suspected Pregnan.
Autoimmune/Lupus
Maj. Intraperit/abd
Anticoag/Bleeding
Healthy Adult
Steroids/Cushings
Cardiac/Thoracic
Fluid or Lyte Loss
Unstable Thyroid
EtoH/DrugAbuse
Ortho Prothesis
Morbid Obesity
Antic
Cardiovascular
TURP, Hysteros
Seizure Meds
Hypertension
Intracranial
Parathyroid
Respiratory
h/o Stoke
Diabetes
Vascular
45-54 y/o
55-69 y/o
Smoking
Hepatic
2u EBL
Renal
70 y/o
TEST
HIV
45
ECG M Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y
CBC+ platelets Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y
Lytes Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y
BUN/Creat Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y
Glucose Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y
LFTs Y Y Y Y Y
Calcium Y
PT/PTT Y Y Y Y Y Y Y Y
U/A(?culture) S
CXR Y S Y S
Hormone Level Y
Bleed Time S
Pregnancy Y
Drug Levels S S
Tumor Markers S
Clot Depends primarily on extensiveness of proposed surgery, as per Blood Bank MSBOS guidelines
Legend: Y usually indicated; M usually indicated for male; S may be requested (and reviewed) by surgeon as part of surgical w/u; if situation acute/severe.
From Halaszynski TM, Juda R, Silverman DG. Optimizing postoperative outcomes with efficient preoperative assessment and management. Crit Care Med 2004;32(4, Suppl):
S76–S86.
Table 1 1 .6 Su r gica l Ca r e Im p rovem en t Project (SCIP) p rocess a n d ou t com e

m ea su r es: in fect ion a n d ven ou s t h rom boem bolism p r op hyla xis
Guideline
SCIP INF 1 Prophylactic antibiotic received within 1 hour before surgical incision
SCIP INF 2 Prophylactic antibiotic selection for surgical patients
SCIP INF 3 Prophylactic antibiotics discontinued within 24 hours after surgery completion time
(48 hours for cardiac patients)
SCIP INF 4 Cardiac surgery patients with controlled 6 AM postoperative serum glucose
SCIP INF 5 Postoperative wound infection diagnosed during index hospitalization (outcome)
SCIP INF 6 Surgery patients with appropriate hair removal
SCIP INF 7 Colorectal surgery patients with immediate postoperative normothermia
SCIP VTE 1 Surgery patients with recommended venous thromboembolism prophylaxis ordered
SCIP VTE 2 Surgery patients who received appropriate venous thromboembolism prophylaxis within
24 hours prior to surgery to 24 hours after surgery
repeatedly demonstrated to confer additional risk of morbid- Table 1 1 .7 Risk a ssessm en t for p u lm on a r y
ity and mortality (1,8). In addition to baseline med ical status, com p lica t ion s in n on ca rd iot h ora cic
additional physiologic d erangements must be evaluated and su r ger y
treated, including the presence of shock, altered volume sta-
tus, electrolyte abnormalities, and anemia. Prompt resuscita- Patient Related Factors
tion, stabilization, and infectious source control comprise the Age 60
basis of treatment. In the presence of acute infection, appro- ASA class II, or greater
priate antibiotics should be given as soon as is feasible. Chronic obstructive pulmonary disease
In som e cases, the risk of d elaying su rgery for fu rther Functional dependence
Congestive heart failure
med ical stabilization is higher than any potential gains. The
Dyspnea at rest or minimal exertion
natu ral history of the d isease and tim ing of su rgical inter-
vention mu st be consid ered . In an analysis of small bow el Operative Factors
obstruction, morbid ity increased in patients requiring small Prolonged surgery ( 3 hours)
Abdominal surgery
bow el resection in ad d ition to ad hesiolysis, suggesting that
Thoracic surgery
timing of intervention potentially impacted care (22). In Neurosurgery
management of acute append icitis, improved outcomes Head and neck surgery
w ere achieved by facilitating time to d efinitive surgery (23). Vascular surgery
Emergency surgery
■ SPECIFIC ORGAN SYSTEMS Use of general anesthesia
Laboratory Values
Robust literatu re exists regard ing preoperative card iac and Serum albumin 3.5
airw ay evalu ation, and these are ad d ressed in ind ivid u al BUN 40
chapters in the text. The m ajority of evid ence in other areas
is less w ell d evelop ed , althou gh the bod y of sup porting lit- Modified from Khuri SF, Henderson WG, Daley J, et al. Successful implementation
erature is increasing. In m any cases, d ata regard ing risk of of the Department of Veterans Affairs’ National Surgical Quality Improvement
Program in the private sector: the Patient Safety in Surgery study. Ann Surg
sp ecific d isease entities is accru ed from organ-sp ecific su r- 2008;248(2):329–336 and Qaseem A, Snow V, Fitterman N, et al. Risk assessment
gery and extrap olated to more general situ ations. A gener- for and strategies to reduce perioperative pulmonary complications for patients
ally accep ted p rinciple is that m ed ical m anagem ent of undergoing noncardiothoracic surgery: a guideline from the American College of
acu te single-system com prom ise p rior to and d uring the Physicians. Ann Intern Med 2006;144(8):575–580.
periop erative p eriod should im prove the patient’s overall
cond ition and low er op erative risk. The follow ing sections lu ng d isease is com m on, occu rs in all ages and may be
review sp ecific recom m end ations for pu lm onary, renal, asym p tom atic. A history of p u lm onary sym p tom s includ -
and hep atic risk assessm ent and m anagem ent. ing chronic cou gh, exercise intolerance, d ysp nea, change in
sp u tu m p rod u ction or p rior p u lm onary com p lications, cig-
arette sm oking, recu rrent p neu m onia, chronic obstru ctive
■ Pulmonary lu ng d isease, reactive airw ay d isease, system ic d isease
Postoperative p u lm onary com p lications are among the w ith p otential p u lm onary involvem ent, occupational
most frequ ent and costly p ostsu rgical events. In noncard iac exp osu res, or p rior lu ng su rgery shou ld be assessed fur-
surgery, p u lm onary com plications occur w ith sim ilar ther. Physical examination find ings m ay inclu d e abnormal
prevalence, and lead to sim ilar increases in m orbid ity, m or- au scu ltation, anatom ic abnorm alities su ch as m orbid obe-
tality, and length of stay as card iac com plications (24). In sity, scoliosis, or chest w all d eform ities, and signs of
ad d ition, the occu rrence of pu lm onary com plications m ay chronic hyp oxia and accessory m u scle resp iration.
be m ore likely to p red ict long term mortality after su rgery
in eld erly p atients (9). ASA Classification. The American Society of Anesthesiologists
In ord er to ad d ress the relative lack of structured recom- (ASA) classification is a measure of comorbidity aimed at pre-
mend ations for preoperative pulmonary evaluation, the d icting p eriop erative m ortality rates, bu t has also d em on-
American College of Physicians issued a summary guideline strated strong correlation w ith p ostop erative p u lm onary
in 2006 (25). Certain patient-related characteristics, operative complication. Substantial increases in pulmonary complica-
factors, and a low serum albumin w ere id entified as risk fac- tion risk occurred w ith increasing ASA class greater than II.
tors for postoperative pulmonary complications. N SQIP
additionally identified elevated blood urea nitrogen (BUN) Age. Age-related d ecreases in p u lm onary fu nction are as-
as a risk factor for postoperative pulmonary complications sociated w ith increased p ostop erative com p lications. In-
(26) and d yspnea at rest or low levels of activity as risk fac- creasing age is an ind ep end ent risk factor for p ostop erative
tors for increased morbid ity and mortality (Table 11.7). com p lications, even after ad ju stm ent for com orbid cond i-
tions (25). Patients aged 60 to 69 w ere tw ice as likely and
Patient-Related Risk Factors p atients aged 70 to 79 w ere three tim es as likely to d evelop
Chronic lu ng d isease is the m ost com m only id entified risk postoperative p u lm onary comp lications w hen comp ared to
factor for p ostop erative pu lm onary com plications. Chronic you nger p atients less than 60 years old . N evertheless, age
alone shou ld not be consid ered a contraind ication to su r- Surgical Site. The site of su rgery influ ences risk for p ostop -
gery in otherw ise healthy patients. erative pulmonary complications. Aortic aneurysm, thoracic
surgery, abd om inal surgery, upper abd ominal surgery, neu-
Congestive Heart Failure. Con gestive h eart failu re h as rosu rgery, p rolonged su rgery, head and neck surgery, vas-
been id entified as an im p ortant p red ictor for p ostop eracu lar su rgery, and em ergency su rgery have been id entified
tive p u lm on ary com p lication s, w ith od d s ratio of 2.93 as p roced u res carrying ad d itional risk of p u lm onary com -
(25). p lications. Thoracotom y and u p p er abd om inal su rgery are
associated w ith the m ost m arked changes in fu nctional
Functional Dependence. Total or partial depend ence on others resid u al cap acity after su rgery.
for perform ing activities of d aily living is a significant risk Risk factors for postop erative com plications after
factor for the d evelop m ent of p ostop erative p u lm onary laparotom y includ e ASA class II, u p p er abd om inal pro-
com plications. ced u res, resid u al intrap eritoneal sep sis, age greater than
59 years, bod y m ass ind ex (BMI) higher than 25 kg/ m 2,
p reop erative stay for longer than 4 d ays, and colorectal or
Restrictive Chest Wall Disease. Specific studies to evaluate the gastrod u od enal su rgery (29).
impact of restrictive chest wall disease, neuromuscular disor- Minim ally invasive ap p roaches have d em onstrated
ders, or pulmonary vascular disease are insufficient to d raw red u ctions in op erative p ain and m u scu loskeletal d ysfunc-
conclusions. These patients may have an impaired ventilatory tion bu t d o not clearly lead to red u ction in p u lm onary com -
reserve as a result of weak muscles or abnormal mechanics of p lications. Physiologic alterations d u e to anesthesia,
ventilation and many physicians will consider these to impart intraperitoneal CO 2 insu fflation, and u nd erlying d isease
additional risk. process may reduce the potential impact of these approaches
and fu rther stu d ies are need ed (30).
Obesity and Obstructive Sleep Apnea. Obesity w as not id en-
tified as carrying sp ecific increased risk for p u lm onary Planned Thoracic Surgery. The American College of Chest
com p lications, bu t m ay be associated w ith obstru ctive Physicians (ACCP) recently u pd ated recommend ations for
sleep ap nea, p ostop erative atelectasis, and d elayed m obi- evaluation of patients w ith lung cancer being consid ered for
lization. An ASA task force observed that the p revalence of resection (31) (Fig. 11.1). Initial pulm onary function testing
sleep d isord ered breathing w as 9% in w om en and 24% in should be performed w ith the patient on optimal bron-
men and conclud ed that perioperative risk increases in pro- chodilator therapy. Findings of significant reduction in Forced
portion to the severity of sleep apnea (27). The literature is Expiratory Volume in 1 second (FEV1) ( 80%) or values below
insu fficient to d raw conclusions on its im pact on specific thresholds for safe resection (2.0 L for pneumonectomy, 1.5 L
com p lications; how ever, p atients w ith obstructive sleep for lobectomy) or a history suggesting dyspnea on minimal
apnea may have associated difficult airway management and exertion or chest rad iograph d em onstrating d iffu se
preoperative status may be improved with the application of p arenchym al abnorm alities shou ld d irect ad d itional pu l-
continu ou s p ositive airw ay pressure (CPAP), noninvasive monary function testing. Further risk stratification is based on
positive pressure ventilation, mandibular advancement d e- measurement of the diffusing capacity of the lung for carbon
vices, oral ap p liances, and p reop erative w eight loss. Intra- dioxide (DLCO 2), estimation of cardiopulmonary exercise tol-
op erative sed ative ad m inistration shou ld be carefu lly erance, and calculation of the postoperative expected FEV1
m on itored and neu rom u scu lar blockad e fu lly reversed and DLCO 2 (see Fig. 11.1). Concurrent epidural anesthesia in
p rior to extu bation. conjunction with general anesthesia has been utilized to blunt
intra-operative shunting and preemptively address postop-
erative pain (32).
Reactive Airway Disease. Asthm a w as not confirm ed to be
an ind ep end ent risk factor for p ostop erative p u lm onary
Duration of Surgery. The d u ration of su rgery, d efined as
com p lications. N evertheless, poorly controlled asthm atics
greater than 3 to 4 hou rs is an ind ep end ent p red ictor of
are at increased risk for pu lm onary com plications, and risk
p ostop erative p u lm onary com p lications (25).
m ay be red u ced by p reop erative m anagem ent aim ed at
elim inating w heezing and targeting peak expiratory flow s
General Anesthesia. General anesthesia m ay d ecrease the
80% of p red icted or the patient’s personal best (28). Step -
fu nctional resid u al cap acity (FRC) for u p to 1 to 2 w eeks
w ise guid ance for management based on severity of asthma
postoperatively. End otracheal intu bation, inhalational anes-
has been pu blished by the N ational Asthma Ed ucation and
thetic, and neu rom u scu lar blockad e m ay contribute to pu l-
Prevention Program (N AEPP).
m onary d ysfu nction. A m eta-analysis of 141 rand om ized
controlled trials of general anesthesia su ggested that the in-
Operative Factors cid ence of p neu m onia and resp iratory failu re d ecreased
Risk assessm ent in elective su rgery can be mod ified by w ith the use of spinal or regional anesthesia (33). It has been
ad ju sting op erative variables: site, d uration, and choice of p rop osed but not p roven that the u se of shorter acting neu-
anesthesia. Em ergency proced ures significantly increase rom u scu lar blocking agents m ay fu rther red u ce risk from
od d s of p u lm onary com p lications. general anesthesia (30).
Pe rform S pirome try

com p lications is obtained w hen high-risk p atients are id en-
tified and interventions are initiated p reop eratively (35,36).
Concentrated efforts d u ring preoperative sessions m ay
FEV1 > 1.5 L lobe ctomy FEV1 < 1.5 L lobe ctomy
FEV1 > 2 L pne umone ctomy FEV1 < 2 L pne umone ctomy resu lt in increased p atient com p liance.
FEV1 > 80% pre dicte d FEV1 < 80% pre dicte d Cigarette sm oking is d irectly toxic to resp iratory ciliary
epithelium and im pairs norm al intratracheal m ucu s trans-
Unexpla ine d dys pne a p ort. In ad d ition, im p aired w ou nd healing and vasosp asm
or diffus e pa re nchyma l increase p ostop erative local com p lications. Despite evi-
dis e a s e on CXR/CT?
d ence in the card iothoracic su rgery p op u lation, surpris-
ingly little evid ence is available in the noncard iac
No Ye s p op u lation. Conflicting evid ence exists regard ing tim ing of
d iscontinu ation of sm oking p rior to su rgery based on
rep orts of increased airw ay reactivity follow ing cessation
Me a s ure DLCO 2
(37,38). A general recom m end ation is that sm oking shou ld
Es tima te %ppo be stop p ed at least 6 to 8 w eeks p reced ing elective surgery.
DLCO 2 > 80% DLCO 2 < 80% FEV1 a nd %ppo
pre dicte d pre dicte d DLCO 2 General m anagem ent to im p rove p reop erative p u l-
m onary statu s inclu d es the u se of short-acting aerosolized
beta2-agonists, leu kotriene inhibitors, steroid s, and bron-
chod ilators w hen necessary to im p rove p u lmonary fu nc-
%ppo FEV1 a nd %ppo FEV1 a nd %ppo FEV1 < 30 or tion. Patients w ith acu te bronchitis, increased secretions, or
%ppo DLCO 2 < 40 %ppo DLCO 2 < 40 %ppo FEV x
1
%ppo DLCO 2 < 1650
change in character of sp u tu m p rod u ction shou ld be
treated w ith a cou rse of antibiotics and elective su rgery
d elayed u ntil sym p tom resolu tion.
Pe rform CP ET Measures aimed at avoiding limited mobilization second-
ary to pain includ e use of minimally invasive vid eoscopic
procedures and the use of thoracic epidural anesthesia, par-
VO 2 ma x > VO 2 ma x 10- VO 2 ma x < ticularly in patients with associated chronic obstructive pul-
15mL/kg/min 15mL/kg/min 10mL/kg/min monary disease (COPD) (39). Postural drainage and chest
physiotherapy are useful in mobilizing secretions but should
Incre a s e d Incre a s e d be reserved for patients with lobar collapse or high sputum
Ave ra ge Ris k
Ris k Ris k production, as they may exacerbate bronchospasm.
FIGURE 11.1. Preoperative evaluation of patients with lung cancer prior to ■ Renal
resection (Adapted from Colice GL, Shafazand S, Griffin JP, et al. Physiologic
evaluation of the patient with lung cancer being considered for resectional sur- Chronic renal disease commonly reflects end organ damage
gery: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest
from systemic conditions such as hypertension, diabetes mel-
2007;132(3, Suppl):161S–177S.) FEV1 Forced Expiratory Volume in 1 second;
CXR Chest X-Ray; CT Computed Tomography; DLCO2 Diffusing capacity of litus, and atherosclerosis, and, once established, is associated
the lung for carbon dioxide; %ppo percent of predicted postoperative; CPET with accelerated development of cardiovascular disease (40).
Cardiopulmonary exercise testing; V̇O2max Maximal oxygen consumption. The overall condition of the patient is related to the extent of
renal impairment as well as the presence of the underlying
Preoperative Testing
disease. Renal function is directly related to the glomerular fil-
The utility of p reop erative pu lm onary fu nction tests, arte- tration rate (GFR), traditionally estimated by the Cockcroft-
rial blood gas analysis, and rou tine chest rad iograp hy in Gault equation (Fig. 11.2) (41). Electrolyte homeostasis,
preventing p ostop erative com plications is d ebatable. Rou - volume status, anemia, and medication excretion may be sig-
tine p reop erative sp irom etry is not recom m end ed in nificantly altered when GFR approaches 30% of baseline.
extrathoracic su rgery. In p atients w ith planned thoracic
proced u res, w ith or w ithou t pu lm onary resection, acu te Preoperative Assessment
sym ptom s, or chronic lung d isease, these shou ld be consid - Acu te interventions su ch as su rgery m ay w orsen alread y
ered as ad juncts to the evaluation. com p rom ised renal fu nction. Preexisting chronic kid ney
d isease is a strong risk factor for the d evelop m ent of p ost-
Perioperative Interventions op erative acu te kid ney inju ry (AKI) (42), w hich is in turn
Lu ng expansion m od alities have been extensively stu d ied strongly associated w ith increased m ortality (43–45). Pre-
and are the only m aneu vers d em onstrated to red uce p u l- op erative renal risk assessm ent centers on d etection of
monary risk (29). Incentive spirom etry and d eep -breathing u nsu spected und erlying renal failure and institu tion of
exercises are inspiratory m aneuvers to recruit alveoli and m easu res to m inim ize fu rther renal insu lt.
counteract the p ostop erative red u ction in FRC. CPAP has The p revalence of chronic kid ney d isease in the ad u lt
been d em onstrated to im p rove postop erative pu lm onary p op u lation is estim ated at 13% (46) and the incid ence of
outcom es (34). A few controlled stud ies in elective su rgical p ostoperative renal failu re in a noncard iac general surgical
patients have d em onstrated that red u ction in pulm onary p op u lation m ay be as high as 1% (44). Analysis of a large
Cock cr oft a n d G a u lt est im a t ion of cr ea t in in e clea ra n ce FIGURE 11.2. Cockcroft and Gault equation estimating creatinine
clearance (mL/min) (40).
CrCl (140 age) IBW/(Cr 72) ( 0.85 for females)
CrCl creatinine clearance; IBW ideal body weight, kg; Cr serum creatinine
IBW: Males 50 kg 2.3 kg for each inch over 5 feet.
Females 45.5 kg 2.3 kg for each inch over 5 feet.
op erative d ataset id entified risk factors for the d evelop - d rugs (NSAIDS), aminoglycosid es, ace-inhibitors, and intra-
ment of AKI in noncard iac su rgical patients (Table 11.8). venou s contrast d ye shou ld be avoid ed . Abd om inal com -
Based on this, the authors d eveloped an AKI scoring sys- p artment synd rom e associated w ith p rerenal oligu ria that
tem w hich correlated the occu rrence of AKI in step w ise fails to resp ond to m ed ical m anagem ent requ ires treatm ent
fashion w ith increasing scores (Table 11.9). w ith d ecom p ressive lap arotom y (49).
Comparison of studies of postoperative renal failure have To date, no pharmacologic intervention has successfully
been hampered by historical lack of a consistent definition improved renal outcomes. Efforts to preserve urinary flow,
and the limitations of serum creatinine in detecting acute including low dose dopamine and furosemide have been
injury. In 2004, the Acute Dialysis Quality Initiative group demonstrated to improve oliguria but not renal function (50).
developed a consensus definition of acute renal failure, A large body of literature concerns attempts to minimize
referred to as the RIFLE (Risk, Injury, Failure, Loss, End-Stage) acute tubular damage from intravenous contrast dye. Pre-
criteria (47) (Table 11.10). These criteria have been utilized in emptive sod ium bicarbonate administration has been associ-
the critical care setting and are being validated in evaluation ated w ith reduced renal failure, but w as not demonstrably
of cardiac, general, and vascular surgical outcomes (45,48). A superior to saline hydration alone (51). Results of prophylac-
single episode of AKI as defined by RIFLE criteria has been tic or therapeutic acetylcysteine administration are variable
found to be associated with long-term mortality in proportion (52). Calcium channel blockers have been associated with
to severity of the insult. Even small changes in creatinine are renoprotection in transplant surgery (53), but have been asso-
associated with increased long-term risk of death, even ciated w ith increased renal failure rates after cardiac surgery
though renal function is observed to have returned to normal (54). Atrial natriuretic peptide (ANP) (55) and insulin-like
at the time of discharge in the vast majority of patients (45). growth factor (56) have demonstrated no improvement in
renal failure rates. Fenoldopam (57,58) has shown some
Perioperative Interventions promise in cardiac surgery and further stud ies are awaited.
Strategies for p revention of p ostop erative renal failu re are Perioperative m anagem ent is aim ed at stabilization of
aim ed at avoid ance of intra-operative hypotension and hom eostatic im balance, ad ju stm ent of m ed ications, and
maintenance of ad equate renal perfusion. Specific nep hro- p revention of p ostop erative renal failu re. Careful evalua-
toxic m ed ications su ch as nonsteroid al anti-inflam m atory tion for intravascu lar volu m e overload , electrolyte abnor-
m alities, and anem ia shou ld be p erform ed .
H yp erkalem ia m ay exist p reop eratively in u p to 38% of
Table 1 1 .8 G en er a l su r ger y a cu t e k id n ey in ju r y p atients w ith chronic renal failu re (59). Ad m inistration of
r isk in d ex intravenou s calcium is im m ed iately ind icated in the pres-
Risk Factor ence of acu te EKG changes. Intracellu lar shift m ay be
achieved w ith sod iu m bicarbonate or insu lin and glucose;
Age 56 yr
how ever, rem oval of excess p otassiu m stores w ill requ ire
Male sex ad m inistration of exchange resins or acu te d ialysis.
Active congestive heart failure Anemia is w ell tolerated in patients w ith chronic renal
Ascites failure. Erythropoietin-stimulating agents are commonly uti-
lized when the GFR is less than 60% and may be associated
Hypertension
with increased thrombotic state. This is often offset by uremic
Emergency surgery coagulopathy related to platelet dysfunction. Desmopressin,
Intraperitoneal surgery conjugated estrogens, blood product transfusion, or dialysis
Renal insufficiency–mild or moderate* may be utilized to minimize coagulopathy.
Altered metabolism and excretion in renal failure man-
Diabetes mellitus–oral or insulin therapy
dates adjustment of d rug dosages. The elevated half-life of
General Surgery Acute Kidney Injury Risk Index classes are based on the number of sedatives and muscle relaxants must be taken into considera-
risk factors the patient possesses: class I (zero, one or two risk factors), class II tion. Prolonged neuromuscular blockade may occur w ith
(three risk factors), class III (four risk factors), class IV(five risk factors), and class V agents that extend drug action at the neuromuscular junc-
(six or more risk factors). tion. Succinylcholine ad ministration leads to increases in
*Preoperative serum creatinine value 1.2 mg/dl.
From Kheterpal S, Tremper KK, Heung M, et al. Development and validation of an
serum potassium and is contraindicated in hyperkalemia.
acute kidney injury risk index for patients undergoing general surgery: results from Atracurium undergoes peripheral Hoffman degradation and
a national data set. Anesthesiology 2009;110(3):505–515. may be utilized preferentially in the face of renal dysfunction.
Table 1 1 .9 G en era l su r ger y a cu t e k id n ey in ju r y r isk in d ex cla ssifi ca t ion syst em

Derivation Cohort, N 57,080 Validation Cohort, N 18,872
Acute Kidney Hazard Ratio Acute Kidney Hazard Ratio

Total Injury Incidence, (95% Confidence Total Injury Incidence, (95% Confidence
Preoperative Risk Class Patients, n % (n) Interval) Patients, n % (n) Interval)
Class I (0–2 risk factors) 31,500 0.2 (66) 10,301 0.2 (25)
Class II (3 risk factors) 12,576 0.8 (104) 4.0 (2.9–5.4) 4,218 0.8 (32) 3.1 (1.9–5.3)
Class III (4 risk factors) 7,933 1.8 (144) 8.8 (6.6–11.8) 2,625 2.0 (53) 8.5 (5.3–13.7)
Class IV(5 risk factors) 3,615 3.3 (118) 16.1 (11.9–21.8) 1,244 3.6 (45) 15.4 (9.4–25.2)
Class V(6 risk factors) 1,456 8.9 (129) 46.3 (34.2–62.6) 484 9.5 (46) 46.2 (26.3–70.9)
Patients are assigned to a risk class based on the number of preoperative risk factors they possess: age 56 yr, male sex, active congestive heart failure, ascites, hyperten-
sion, emergency surgery, intraperitoneal surgery, renal insufficiency (serum creatinine 1.2 mg/dl), and diabetes mellitus (oral or insulin therapy).
From Kheterpal S, Tremper KK, Heung M, et al. Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national
data set. Anesthesiology 2009;110(3):505–515.
Renal replacem ent therapy is u su ally ind icated once the tis, transfu sion, variceal bleed ing, p rior anesthetic hepato-
GFR falls below 5 to 10 m L/ m in. Routine d ialysis should be toxicity, bleed ing d isord ers, biliary stone d isease, fam ily
undertaken 24 hours before elective surgery to allow the history of enzym e d eficiencies and prior malignancy
patient to stabilize after treatment. More emergent treat- shou ld trigger fu rther investigation. Physical exam ination
ment is ind icated for correction of acid osis, hyperkalemia, find ings of jau nd ice, ascites, hep atosp lenom egaly, palm ar
severe volu m e overload , and pericard itis or prior to em er- erythem a, abd om inal varices, and asterixis m ay be signs of
gent surgery. Continuous venovenous hem od ialysis m ay be severe hep atic d erangem ent. Com p rom ised synthetic fu nc-
ind icated to relieve volume overload in the hemod ynami- tion m ay m anifest as elevations in p rothrom bin tim e and
cally unstable patient. Subclavian access should be avoid ed international norm alized ratio (IN R). Throm bocytopenia
in patients w ho w ill need permanent access because of the second ary to sp lenic sequ estration m ay be an early sign of
unacceptably high incid ence of subclavian vein stenosis. p reviou sly u nd iagnosed p ortal hyp ertension. If liver d is-
ease is su sp ected on initial evalu ation, elective surgery
shou ld be d eferred for fu rther w orku p (60).
■ Hepatic
The liver p lays a p rotean role in m etabolism and its central Acute Hepatitis
anatom ic location in the m esenteric circu lation fu rther Acute hepatitis may d evelop second ary to alcohol or other
increases the im pact of intra-abd om inal surgical proce- d ru g ingestion or viral infection. Mortality rates for su rgery
d u res on hep atic fu nction. Risk assessment is based on the are high: old er reports cite 10% follow ing open liver biopsy
severity of u nd erlying liver d isease, the type of su rgery, in viral hepatitis and 55% to 100% in patients w ith acute
and the anesthetic u sed . alcoholic hepatitis und ergoing open liver biopsy or laparo-
Patients w ith chronic liver d isease m ay be asym pto- tom y. Consid erable recovery m ay occur follow ing the initial
matic and liver fu nction tests m ay not correlate w ith the insult and elective surgery should be d eferred until several
extent of u nd erlying hepatic d ysfu nction. The history and w eeks after normalization of liver fu nction tests. For acute
physical exam ination is critical in d etecting u nsu sp ected alcoholic hep atitis, abstinence from alcohol for 12 w eeks
d isease. Prior history of alcohol or su bstance abuse, hep ati- before elective surgery has been recommend ed .
Table 1 1 .1 0 Th e RIFLE cla ssifi ca t ion for a cu t e r en a l fa ilu r e

Urine Output Criteria CFR Criteria
Risk (R) 0.5 mL/kg/hr 6 hrs Increased [creat] 1.5 or GFR decrease of 25%
Injury (I) 0.5 mL/kg/hr 12 hrs Increased [creat] 2 or GFR decrease of 50%
Failure (F) 0.3 mL/kg/hr 24 hrs or Increased [creat] 3 or GFR decrease of 75%
anuria for 12 hrs or [creat] 4 mg/dL
Loss (L) N/A Persistent ARF (“F”) for 4 wks but 3 mos
End-stage renal N/A Persistent renal failure (“F”) for 3 mos
disease (E)
GRF, glomerular filtration rate; [creat], serum creatinine concentration; N/A, not applicable; ARF, acute renal failure.
From Kellum JA, Bellomo R, Ronco C. Classification of acute kidney injury using RIFLE: What’s the purpose? Crit Care Med
2007;35(8):1983–1984.
M od ifi ed Ch ild -Tu rcot t e-Pu gh (CTP) Scor e FIGURE 11.3. Modified Child-Turcotte-Pugh
score (Adapted from Child CG, Turcotte J G.
Score Surgery and portal hypertension. Major Probl
1 point 2 points 3 points Clin Surg 1964;1:1–85; Pugh RN, Murray-Lyon
IM, Dawson J L, et al. Transection of the
Total serum bilirubin 3.4 3.4 5.0 5.0 oesophagus for bleeding oesophageal varices.
(umol/dL) Br J Surg 1973;60:646–649.)
Serum albumin 3.5 2.8 – 3.5 2.8

(g/dL)
International 1.7 1.7 – 2.2 2.2

normalized ratio
Ascites None Controlled with Treatment

medication refractory
Encephalopathy None Grade I–II or Grade III–IV
controlled with or treatment
medication refractory
Sum total points for each component:
Total Points Surgical Mortality

Class A 5–6 10%
Class B 7–9 30%
Class C 10–15 80%
Chronic Liver Disease erative risk assessm ent algorithm based on these scores has
Risk assessm ent in chronic liver d isease is largely based on been su ggested (Fig. 11.5)
stu d ies of ou tcom e in p atients u nd ergoing su rgery for p or- In general, patients with compensated chronic liver disease
tal hyp ertension (Mod ified Child -Tu rcotte-Pu gh score, Fig. can tolerate most surgical procedures well; patients with
11.3) (61,62) and su rvival m od els for patients w ith end - decompensated cirrhosis have significant surgical morbidity
stage liver d isease (Mod el for End Stage Liver Disease, and mortality proportional to the degree of hepatic dysfunc-
MELD score, Fig. 11.4) (63–65). Surgical risk in cirrhotic tion. Intra-abdominal (67,68) and cardiac surgery (69) have
patients ap p ears to correlate w ith these scoring system s, been associated with high mortality rates in cirrhotics. In one
w ith the p resence of infection, preoperative u p p er gas- series, patients with cirrhosis undergoing surgery had a 30-day
trointestinal bleed ing, intra-op erative hypotension, associ- mortality of 11.6% and an overall complication rate of 30%,
ated renal failu re or COPD, em ergency or abd om inal most frequently pneumonia (66). Complications included
proced u res correlating w ith poorer ou tcom es (66). A p reop - bleeding, hepatic decompensation, sepsis, and renal failure.
M ELD Scor e FIGURE 11.4. Model end-stage liver dis-

ease score (Adapted from Kamath PS,
MELD score (9.6 loge [creatinine mg/dL]) (3.8 loge [bilirubin mg/dL]) Wiesner RH, Malinchoc M, et al. A model to
(11.2 loge [international normalized ratio]) 6.4 predict survival in patients with end-stage
liver disease. Hepatology2001;33:464–470.)
Minimum laboratory value is 1.0 (for laboratory values less than 1.0, use value of 1.0)
Maximum creatinine is 4.0 (for creatinine 4.0, use value of 4.0) if patient has had dialysis twice within the
previous week, use value of 4.0
Round final score to nearest whole number
Maximum score is 40
90-day mortality for hospitalized patients

MELD score Mortality
40 100%
30–39 83%
20–29 76%
10–19 27%
10 4%
Acute De fe r s urge ry
he pa titis until the
Acute condition improve s
live r
dis e a s e
Fulmina nt Cons ide r ca ndida cy
he pa tic fa ilure for live r
CTP cla s s C tra ns pla nta tion
or
MELD s core >15 Cons ide r
a lte rna tive
to s urge ry
Known or As s e s s CTP CTP cla s s B P roce e d with

s us pe cte d or or ca ution a nd clos e
cirrhos is MELD s core MELD s core 10 –15 pe riope ra tive
monitoring
Chronic
live r CTP cla s s A
dis e a s e or
MELD s core <10
No cirrhos is P roce e d with

s urge ry
FIGURE 11.5. Proposed algorithm for evaluation of patients with liver disease (Adapted from Hanje AJ , Patel T. Preoperative
evaluation of patients with liver disease. Nat Clin Pract Gastroenterol Hepatol 2007;4:266–276.)
Cholestasis correlate with postoperative mortality and may be utilized in

Cholestasis has been associated w ith increased operative decision-making. Patients with significant steatohepatitis may
risk, particularly in the presence of biliary tract infection. have higher mortality follow ing major anatomic resection.
Cholangitis should be treated promptly w ith d ecompression
and systemic antibiotics. Risk factors reported for postopera- Perioperative Interventions
tive complications in patients w ith obstructive jaund ice Preoperative measures d irected at minimizing surgical com-
includ e anemia, bilirubin 11 mg/ d L, malignancy, hypoal- plications second ary to liver d ysfunction includ e manage-
buminemia, infection, and azotemia (70). Acute renal failure ment of portal hypertension, cholestasis, and coagulopathy,
w ith renal tubular d ysfunction has been reported in approx- and prevention of further hepatic compromise. Evid ence
imately 9% of postoperative patients (71) w ith the risk being that modifying risk category affects outcome is not strong,
apparently related to degree of hyperbilirubinemia and the but med ical management inherently seems important.
presence of infection. Empiric preoperative biliary drainage, Intra-op erative m anagem ent is d irected at m aintaining
either percutaneously or endoscopically has been recom- p erfusion to avoid p recipitating fu rther ischem ic injury.
mend ed for patients w ith biliary obstruction, but manage- Inhalational anesthetics red uce card iac outpu t and hepatic
ment should be ind ivid ualized . blood flow ; isoflu rane m ay be the p referred agent to m ini-
m ize this. Direct hep atotoxicity m ay occu r, historically
Other w ith halothane, bu t w ith less frequ ency w ith new er agents
NASH. N onalcoholic steatohep atitis (N ASH ) is an often su ch as sevoflu rane. Sed ative and narcotic m etabolism
silent d isease affecting 2% to 5% of Am ericans, particu larly m ay be altered in severe hep atic d ysfu nction. As the d egree
m id d le-aged and overw eight or obese p atients. The etiol- of hep atic d ysfu nction is not easily qu antified , d ose ad just-
ogy is u nclear and the cou rse m ay p rogress silently to cir- m ent is often titrated to effect.
rhosis. The incid ence of fatty liver in patients u nd ergoing The p resence of p ortal hyp ertension m and ates m eticu -
bariatric su rgery is high and unsuspected cirrhosis is fou nd lou s su rgical techniqu e. Managem ent of p ortal hyp erten-
in 6% (72). N o sp ecific m easu res to prevent or treat the d ys- sion may include beta-blockade, octreotide, and transvenou s
fu nction have been id entified . Su rgical risk ap p ears to be intrahep atic p ortosystem ic shu nting. Volu me m anagem ent
linked to the d egree of cirrhosis present. is com p licated by high ou tp u t card iac failu re, p erip heral
arteriovenou s shu nting, and d istu rbed salt-conservation
Hepatic resection. There is little form al gu id ance regard ing second ary to hyp erald osteronem ia. Postop erative volum e
estim ation of ability to tolerate hep atic resection in cirrhotic shifts superim posed on the u nd erlying vasod ilatory state
p atien ts. MELD an d Child -Tu rcotte-Pu gh (CTP) scores of liver d isease m ay lead to p rogressive renal failu re.
Carefu l m onitoring w ith jud iciou s resu scitation m ay 3. Davenp ort DL, H end erson WG, Khu ri SF, et al. Preop erative risk fac-
tors and su rgical com p lexity are m ore p red ictive of costs than p ostop -
im prove ou tcom es. erative com p lications: a case stud y u sing the N ational Surgical Quality
The coagu lop athy of liver failu re is m u ltifactorial; Im p rovem ent Program (N SQIP) d atabase. Ann Surg 2005;242(4):
d ecreased absorp tion of fat soluble vitam in K associated 463–468; d iscu ssion 68–71.
4. Khuri SF. The N SQIP: a new frontier in su rgery. Surgery 2005;138(5):
w ith obstru ctive jau nd ice, p oor nu tritional intake, and fail- 837–843.
ure of synthetic fu nction in patients w ith p arenchym al d is- 5. Khuri SF, H end erson WG, Daley J, et al. Su ccessfu l im p lem entation of
ease all m ay contribu te. Concomitant throm bocytop enia the Dep artm ent of Veterans Affairs’ N ational Su rgical Qu ality
Im p rovem ent Program in the private sector: the Patient Safety in
may be present second ary to splenic sequ estration in portal Su rgery stud y. Ann Surg 2008;248(2):329–336.
hyp ertension. Dissem inated intravascular coagu lation 6. Ghaferi AA, Birkm eyer JD, Dim ick JB. Variation in hosp ital m ortality
(DIC) m ay be p resent second ary to low grad e biliary sep- associated w ith inp atient su rgery. N Engl J Med 2009;361(14):1368–75.
7. N ap olitano LM. Stand ard ization of p eriop erative m anagem ent: clinical
sis. Treatm ent is supp ortive and inclu d es vitam in K ad m in- pathw ays. Surg Clin North Am 2005;85(6):1321–1327, xiii.
istration, fresh frozen plasm a, and p latelet transfu sion. 8. Khuri SF, H end erson WG, DePalm a RG, et al. Determ inants of long-
DDAVP and inhibitors of fibrinolysis m ay also be u tilized . term su rvival after m ajor su rgery and the ad verse effect of p ostop era-
tive com plications. Ann Surg 2005;242(3):326–341; d iscu ssion 41–43.
Su ccessfu l correction of severe coagu lop athy has been 9. Manku K, Bacchetti P, Leu ng JM. Prognostic significance of p ostop era-
rep orted w ith off-label u se of Factor rVIIa, bu t enthu siasm tive in-hosp ital com p lications in eld erly p atients. I. Long-term su r-
is w aning in the w ake of reports of ad verse throm botic vival. Anesth Analg 2003;96(2):583–589, table of contents.
10. H alaszynski TM, Jud a R, Silverm an DG. Op tim izing p ostop erative
events (73). outcom es w ith efficient preoperative assessm ent and m anagem ent.
Delayed w ou nd healing and w ou nd infection are likely Crit Care Med 2004;32(4, Su p p l):S76–S86.
to be exacerbated by associated malnutrition, m alignancy, 11. Fischer SP. Develop m ent and effectiveness of an anesthesia p reop era-
tive evalu ation clinic in a teaching hosp ital. Anesthesiology 1996;85(1):
and sep sis. N u tritional d eficiencies m ay inclu d e hyp om ag- 196–206.
nesem ia and hypophosphatemia as w ell as protein-calorie 12. Pollard JB, Zboray AL, Mazze RI. Econom ic benefits attribu ted to op en-
d eficits. Postop erative nutritional su pplem entation m ay be ing a preoperative evalu ation clinic for ou tp atients. Anesth Analg 1996;
83(2):407–410.
ham pered by the d evelop m ent of encephalopathy and 13. Bru m field VC, Kee CC, Johnson JY. Preop erative p atient teaching in
intolerance of enteral protein load ing. Ascites shou ld be am bu latory surgery settings. AORN J 1996;64(6):941–946, 948, 951–952.
managed w ith volum e restriction, active d iu resis, and 14. Kluger MT, Gale S, Plu m m er JL, et al. Peri-op erative d ru g p rescribing
p attern and m anu facturers’ gu id elines. An au d it. Anaesthesia 1991;
paracentesis to red u ce intra-abd om inal pressure and the 46(6):456–459.
incid ence of abd om inal w ound d isru ption. 15. Ang-Lee MK, Moss J, Yu an CS. H erbal m ed icines and p eriop erative
Encep halop athy m ay be p recip itated by su rgical stress, care. JAMA 2001;286(2):208–216.
16. Kaye AD, Clarke RC, Sabar R, et al. H erbal m ed icines: cu rrent trend s in
sep sis, and volu m e shifts and aggravated by analgesic anesthesiology practice–a hosp ital su rvey. J Clin Anesth 2000;12(6):
med ication. N o specific prophylaxis is recom m end ed other 468–471.
than carefu l m ed ical m anagem ent and ju d iciou s sed ation 17. Schein OD, Katz J, Bass EB, et al. The valu e of rou tine p reop erative
m ed ical testing before cataract su rgery. Stu d y of Med ical Testing for
use. Exacerbations are m anaged w ith lactu lose titrated to 2 Cataract Su rgery. N Engl J Med 2000;342(3):168–175.
to 3 loose stools d aily and oral antim icrobial agents su ch as 18. Perez A, Planell J, Bacard az C, et al. Valu e of rou tine p reop erative tests:
neom ycin or rifaxim in to red uce fecal flora and m inim ize a m u lticentre stu d y in fou r general hosp itals. Br J Anaesth 1995;74(3):
250–256.
bacterial translocation. 19. Dzankic S, Pastor D, Gonzalez C, et al. The p revalence and p red ictive
Acu te severe alcoh ol w ith d raw al, d eliriu m trem ens valu e of abnorm al p reop erative laboratory tests in eld erly su rgical
(DTs), is classically seen 72 hou rs after cessation of alco- patients. Anesth Analg 2001;93(2):301–308, 2nd contents p age.
20. Am erican Society of Anesthesiologists Task Force on Preanesthesia
hol u se, bu t m ay be seen earlier. Desp ite treatm ent, m or- Evaluation. Practice ad visory for p reanesthesia evalu ation: a rep ort by
tality rem ains 5% to 15%. The hallm ark is au tonom ic the Am erican Society of Anesthesiologists Task Force on Preanesthesia
instability, w ith hyp ertension, tachycard ia, sw eating, Evaluation. Anesthesiology 2002;96(2):485–496.
21. Griffin FA. Red u cing su rgical com p lications. Jt Comm J Qual Patient Saf
an xiety, and visu al hallu cination s. Th e m ainstay of treat- 2007;33(11):660–665.
m en t is benzod iazep ines, w ith sym p tom atic treatm en t 22. Margenthaler JA, Longo WE, Virgo KS, et al. Risk factors for ad verse
w ith beta-blockers or clon id ine. Sym p tom -triggered ou tcom es follow ing su rgery for sm all bow el obstru ction. Ann Surg
2006;243(4):456–464.
m ed ication regim en s are associated w ith red u ction in 23. Earley AS, Pryor JP, Kim PK, et al. An acute care surgery mod el improves
total m ed ication d ose com p ared to stand ing regim ens outcomes in patients with append icitis. Ann Surg 2006;244(4):498–504.
(74); p harm acologic DT p rop hylaxis is not ind icated 24. Sm etana GW, Law rence VA, Cornell JE. Preop erative p u lm onary risk
stratification for noncard iothoracic su rgery: system atic review for the
excep t in high-risk cases. Other su p p ortive therap y Am erican College of Physicians. Ann Intern Med 2006;144(8):581–595.
inclu d es thiam ine, folate, and m u ltivitam in ad m inistra- 25. Qaseem A, Snow V, Fitterm an N , et al. Risk assessm ent for and strate-
tion, intraven ou s flu id and electrolyte rep lacem en t. gies to red u ce p eriop erative p u lm onary com p lications for p atients
u nd ergoing noncard iothoracic su rgery: a gu id eline from the Am erican
College of Physicians. Ann Intern Med 2006;144(8):575–580.
■ REFERENCES 26. Arozu llah AM, Daley J, H end erson WG, et al. Mu ltifactorial risk ind ex
for pred icting postoperative respiratory failure in m en after m ajor non-
1. Khuri SF, Daley J, H end erson W, et al. The Dep artm ent of Veterans card iac su rgery. The N ational Veterans Ad m inistration Su rgical Qu al-
Affairs’ N SQIP: the first national, valid ated , ou tcom e-based , risk- ity Im p rovem ent Program . Ann Surg 2000;232(2):242–253.
ad justed , and peer-controlled p rogram for the m easurem ent and 27. Gross JB, Bachenberg KL, Benu m of JL, et al. Practice gu id elines for the
enhancem ent of the qu ality of su rgical care. N ational VA Su rgical Qu al- periop erative m anagem ent of patients w ith obstructive sleep apnea: a
ity Im provem ent Program . Ann Surg 1998;228(4):491–507. report by the Am erican Society of Anesthesiologists Task Force on Peri-
2. Collins TC, Daley J, Henderson WH, et al. Risk factors for prolonged op erative Managem ent of p atients w ith obstru ctive sleep ap nea. Anes-
length of stay after m ajor elective surgery. Ann Surg 1999;230(2):251–259. thesiology 2006;104(5):1081–1093; qu iz 117–118.
28. Sw eitzer BJ, Sm etana GW. Id entification and evalu ation of the p atient 50. Mahesh B, Yim B, Robson D, et al. Does fu rosem id e p revent renal d ys-
w ith lu ng d isease. Med Clin North Am 2009;93(5):1017–1030. function in high-risk card iac su rgical patients? Resu lts of a d ou ble-
29. H all JC, Tarala RA, H all JL, et al. A m u ltivariate analysis of the risk of blind ed prospective rand om ised trial. Eur J Cardiothorac Surg 2008;
p u lm onary com p lications after lap arotom y. Chest 1991;99(4):923–927. 33(3):370–376.
30. Law rence VA, Cornell JE, Sm etana GW. Strategies to red u ce p ostop era- 51. Brar SS, Shen AY, Jorgensen MB, et al. Sod iu m bicarbonate vs sod iu m
tive p ulm onary com plications after noncard iothoracic surgery: sys- chlorid e for the p revention of contrast m ed iu m -ind u ced nep hrop athy
tem atic review for the Am erican College of Physicians. Ann Intern Med in patients und ergoing coronary angiography: a rand om ized trial.
2006;144(8):596–608. JAMA 2008;300(9):1038–1046.
31. Colice GL, Shafazand S, Griffin JP, et al. Physiologic evalu ation of the 52. Fishbane S. N -acetylcysteine in the p revention of contrast-ind u ced
p atient w ith lung cancer being consid ered for resectional su rgery: nephrop athy. Clin J Am Soc Nephrol 2008;3(1):281–287.
ACCP evid enced -based clinical p ractice gu id elines (2nd ed ition). Chest 53. Wagner K, Albrecht S, N eu m ayer H H . Prevention of p osttransp lant
2007;132(3, Su pp l):161S–177S. acute tubu lar necrosis by the calcium antagonist d iltiazem : a p rospec-
32. Von Dossow V, Welte M, Zau ne U, et al. Thoracic ep id u ral anesthesia tive rand om ized stu d y. Am J Nephrol 1987;7(4):287–291.
com bined w ith general anesthesia: the preferred anesthetic techniqu e 54. You ng EW, Diab A, Kirsh MM. Intravenou s d iltiazem and acu te renal
for thoracic su rgery. Anesth Analg 2001;92(4):848–854. failure after card iac op erations. Ann Thorac Surg 1998;65(5):1316–1319.
33. Rod gers A, Walker N , Schu g S, et al. Red u ction of p ostop erative m or- 55. Allgren RL, Marbu ry TC, Rahm an SN , et al. Anaritid e in acu te tu bu lar
tality and m orbid ity w ith epid ural or spinal anaesthesia: resu lts from necrosis. Au ricu lin Anaritid e Acu te Renal Failu re Stu d y Grou p . N Engl
overview of rand om ised trials. BMJ 2000;321(7275):1493. J Med 1997;336(12):828–834.
34. Zarbock A, Mu eller E, N etzer S, et al. Prop hylactic nasal continuou s 56. H irschberg R, Kop p le J, Lipsett P, et al. Mu lticenter clinical trial of
p ositive airw ay p ressu re follow ing card iac su rgery p rotects from p ost- recom binant hum an insu lin-like grow th factor I in patients w ith acute
op erative pu lm onary com p lications: a p rosp ective, rand om ized , con- renal failure. Kidney Int 1999;55(6):2423–2432.
trolled trial in 500 patients. Chest 2009;135(5):1252–1259. 57. Bove T, Land oni G, Calabro MG, et al. Renop rotective action of
35. Torrington KG, H end erson CJ. Periop erative resp iratory therap y fenold opam in high-risk patients u nd ergoing card iac surgery: a
(PORT). A p rogram of p reop erative risk assessm ent and ind ivid u alized p rosp ective, d ou ble-blind , rand om ized clinical trial. Circulation
p ostoperative care. Chest 1988;93(5):946–951. 2005;111(24):3230–3235.
36. H u lzebos EH , H eld ers PJ, Favie N J, et al. Preop erative intensive insp i- 58. Land oni G, Biond i-Zoccai GG, Tu m lin JA, et al. Beneficial im p act of
ratory m u scle training to prevent postoperative p ulm onary com plica- fenold opam in critically ill patients w ith or at risk for acu te renal fail-
tions in high-risk patients u nd ergoing CABG surgery: a rand om ized u re: a m eta-analysis of rand om ized clinical trials. Am J Kidney Dis
clinical trial. JAMA 2006;296(15):1851–1857. 2007;49(1):56–68.
37. Barrera R, Shi W, Am ar D, et al. Sm oking and tim ing of cessation: 59. Krishnan M. Preop erative care of p atients w ith kid ney d isease. Am Fam
im pact on pu lm onary com p lications after thoracotom y. Chest 2005; Physician 2002;66(8):1471–1476, 1479.
127(6):1977–1983. 60. O’Leary JG, Yachim ski PS, Fried m an LS. Su rgery in the p atient w ith
38. N akagaw a M, Tanaka H , Tsu ku m a H , et al. Relationship betw een the liver d isease. Clin Liver Dis 2009;13(2):211–231.
d u ration of the p reop erative sm oke-free p eriod and the incid ence of 61. Child CG, Turcotte JG. Su rgery and p ortal hyp ertension. Major Probl
p ostoperative p ulm onary com p lications after p u lm onary su rgery. Clin Surg 1964;1:1–85.
Chest 2001;120(3):705–710. 62. Pu gh RN , Mu rray-Lyon IM, Daw son JL, et al. Transection of the
39. Licker MJ, Wid ikker I, Robert J, et al. Op erative m ortality and respira- oesop hagus for bleed ing oesop hageal varices. Br J Surg 1973;60(8):
tory com plications after lung resection for cancer: im pact of chronic 646–649.
obstructive pu lm onary d isease and tim e trend s. Ann Thorac Surg 63. Kam ath PS, Wiesner RH , Malinchoc M, et al. A m od el to p red ict su r-
2006;81(5):1830–1837. vival in patients w ith end -stage liver d isease. Hepatology 2001;33(2):
40. Sarnak MJ, Levey AS, Schoolw erth AC, et al. Kid ney d isease as a risk 464–470.
factor for d evelop m ent of card iovascu lar d isease: a statem ent from the 64. N orthu p PG, Wanam aker RC, Lee VD, et al. Mod el for End -Stage Liver
Am erican H eart Association Councils on Kid ney in Card iovascu lar Disease (MELD) p red icts nontransplant surgical m ortality in patients
Disease, H igh Blood Pressu re Research, Clinical Card iology, and Ep i- w ith cirrhosis. Ann Surg 2005;242(2):244–251.
d em iology and Prevention. Circulation 2003;108(17):2154–2169. 65. Farnsw orth N , Fagan SP, Berger DH , et al. Child -Tu rcotte-Pu gh versu s
41. Cockcroft DW, Gau lt MH . Pred iction of creatinine clearance from MELD score as a p red ictor of ou tcom e after elective and em ergent su r-
seru m creatinine. Nephron 1976;16(1):31–41. gery in cirrhotic p atients. Am J Surg 2004;188(5):580–583.
42. Waikar SS, Liu KD, Chertow GM. Diagnosis, ep id em iology and ou t- 66. Ziser A, Plevak DJ, Wiesner RH , et al. Morbid ity and m ortality in cir-
com es of acu te kid ney inju ry. Clin J Am Soc Nephrol 2008;3(3):844– rhotic p atients u nd ergoing anesthesia and su rgery. Anesthesiology
861. 1999;90(1):42–53.
43. Chertow GM, Levy EM, H am m erm eister KE, et al. Ind ep end ent associ- 67. Meu nier K, Mu cci S, Qu entin V, et al. Colorectal su rgery in cirrhotic
ation betw een acute renal failu re and m ortality follow ing card iac su r- p atients: assessm ent of op erative m orbid ity and m ortality. Dis Colon
gery. Am J Med 1998;104(4):343–348. Rectum 2008;51(8):1225–1231.
44. Kheterpal S, Trem per KK, H eu ng M, et al. Develop m ent and valid ation 68. Lehnert T, H erfarth C. Pep tic u lcer su rgery in p atients w ith liver cir-
of an acu te kid ney inju ry risk ind ex for patients u nd ergoing general rhosis. Ann Surg 1993;217(4):338–346.
su rgery: resu lts from a national d ata set. Anesthesiology 2009;110(3): 69. Su m an A, Barnes DS, Zein N N , et al. Pred icting ou tcom e after card iac
505–515. surgery in patients w ith cirrhosis: a com parison of Child -Pu gh and
45. Bihorac A, Yavas S, Subbiah S, et al. Long-term risk of m ortality and MELD scores. Clin Gastroenterol Hepatol 2004;2(8):719–723.
acu te kid ney inju ry d u ring hosp italization after m ajor su rgery. Ann 70. Fried m an LS. The risk of su rgery in p atients w ith liver d isease. Hepatol-
Surg 2009;249(5):851–858. ogy 1999;29(6):1617–1623.
46. Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kid ney d is- 71. Wait RB, Kahng KU. Renal failu re com p licating obstru ctive jau nd ice.
ease in the United States. JAMA 2007;298(17):2038–2047. Am J Surg 1989;157(2):256–263.
47. Bellom o R, Ronco C, Kellu m JA, et al. Acu te renal failu re – d efinition, 72. Brolin RE, Brad ley LJ, Taliw al RV. Unsu sp ected cirrhosis d iscovered
ou tcom e m easures, anim al m od els, flu id therap y and inform ation tech- d u ring elective obesity op erations. Arch Surg 1998;133(1):84–88.
nology need s: the Second International Consensu s Conference of the 73. O’Connell KA, Wood JJ, Wise RP, et al. Throm boem bolic ad verse
Acute Dialysis Qu ality Initiative (ADQI) Grou p . Crit Care 2004;8(4): events after u se of recom binant hu m an coagu lation factor VIIa. JAMA
R204–R212. 2006;295(3):293–298.
48. Ku itunen A, Vento A, Su ojaranta-Ylinen R, et al. Acu te renal failu re 74. Jaeger TM, Lohr RH , Pankratz VS. Sym p tom -triggered therap y for
after card iac surgery: evalu ation of the RIFLE classification. Ann Thorac alcohol w ithd raw al synd rom e in m ed ical inp atients. Mayo Clin Proc
Surg 2006;81(2):542–546. 2001;76(7):695–701.
49. Cheatham ML, Malbrain ML, Kirkp atrick A, et al. Resu lts from the 75. Kellum JA, Bellom o R, Ronco C. Classification of acu te kid ney inju ry
International Conference of Experts on Intra-abd om inal H ypertension u sing RIFLE: w hat’s the p u rp ose? Crit Care Med 2007;35(8):1983–1984.
and Abd om inal Com partm ent Synd rom e. II. Recom m end ations. Inten- 76. H anje AJ, Patel T. Preop erative evalu ation of p atients w ith liver d is-
sive Care Med 2007;33(6):951–962. ease. Nat Clin Pract Gastroenterol Hepatol 2007;4(5):266–276.
CHAPTER
12
Anesthesia Complications
Paul E. Kazanjian
■ INTRODUCTION inju ry, and the ou tcom e of litigation. A p hysician review s

the case, rates the severity of inju ry, and d eterm ines the
There are a w id e variety of com p lications in anesthesiology p otential for p revention and ap p rop riateness of anesthesia
ranging from relatively frequ ent and m inor ad verse events care. Claims are sep arated into tw o categories: d am aging
to rare bu t d isastrou s outcom es, includ ing brain d am age events and com p lications. The d am aging event is the spe-
and d eath. The anesthesiologist’s expertise in m anagem ent cific incid ent that lead s to the com p lication, w hile the com -
of the airw ay is cru cial to the safe cond u ct of anesthesia p lication is the inju ry that the p atient su stained . The
care. Unfortu nately, airw ay com plications are a m ajor find ings are rep orted in the scientific literatu re and a num -
sou rce of seriou s m orbid ity and m ortality. Anesthetic m ed - ber of these articles have been referenced in this chapter.
ications play a cru cial role in rend ering patients insensate, More inform ation abou t the p roject and a com p lete bibliog-
im m obile, and u nconscious but they also accou nt for a rap hy is available on the American Society of Anesthesiolo-
nu m ber of ad verse effects and com plications. Machines are gists’ (ASA) Closed Claim s Project Web site (1).
used to ad m inister d rug infu sions, ventilate the lu ngs, There are lim itations to closed claim s analysis includ ing
measu re the blood pressure, and d eliver volatile anesthet- lack of d ata regard ing the total popu lation at risk for injury
ics and oxygen. Machines can breakd ow n or be m isu sed , and nonrand om, retrospective d ata collection. For several
som etim es resu lting in p atient inju ry. Like surgery, anes- reasons, it is not possible to provid e nu m erical estim ates of
thesiology is a p roced u re-oriented field and som e com - risk or establish true incid ence rates based on closed claims
p lications resu lt from technical m ishap s or u ntow ard analysis. All ad verse ou tcomes d o not resu lt in a malprac-
patient-d evice interactions. tice claim and 40% of p racticing anesthesiologists are not
Whole textbooks are d evoted to the su bject of com p lica- includ ed in the analysis becau se their insurance com panies
tions in anesthesia and this one chap ter cannot cover the d o not participate in the Closed Claims Project. It is not pos-
entire su bject. This chapter serves as a starting p oint for sible to d etermine w hether increases or d ecreases in cases
su rgeons interested in an introd u ction to the gam u t of com - over time represent actual changes in the rate of complica-
plications d u e to anesthesia. Also, the references at the end tions, a m ore or less litigiou s patient popu lation or both.
of the chap ter are good resou rces for those interested in
more inform ation about ind ivid u al types of anesthesia-
related com p lications. ■ AIRWAY COMPLICATIONS
Throu ghou t this chapter, there are references to The
Management of the airw ay is a central activity of daily anes-
American Society of Anesthesiologists Closed Claim s
thetic practice and it involves a variety of maneuvers and
Database. The Closed Claim s Project w as begu n in 1984 in
d evices designed to support or maintain adequate oxygena-
resp onse to rising p rofessional liability prem iu m s. The
tion and ventilation w hile the patient is not fully capable of
intention w as to id entify anesthetic-related com plications,
d oing so himself. Techniques range from simple maneuvers
im p rove p atient safety, and im prove the insu rance p roblem
to maintain airw ay patency d uring spontaneous ventilation
for anesthesiologists. The project is an ongoing evalu ation
to fiberoptic intubation of the trachea in patients w ho are dif-
and in-d ep th analysis of nearly 9000 closed claim s from 35
ficult to intubate. Problems occurring d uring management of
professional liability insu rance com panies covering 60% of
the airway are the most important cause of major anesthetic-
the anesthesiologists in the United States. Each case is
related morbidity and mortality. In an analysis of closed
d escribed by a brief narrative sum m ary d escribing the
claims in the American Society of Anesthesiologists Closed
claim , p atient inform ation, su rgical proced ure and p osi-
Claims Project, respiratory events are the single largest class
tioning, p reanesthetic evaluation, anesthetic techniqu e,
of incidents leading to injury, accounting for 30% of claims in
events lead ing to the inju ry or claim , type and severity of
adults and 43% of claims in pediatric patients (2). Most of the
adverse respiratory events were due to difficulty managing
Paul E. Kazanjian: Dep artm ent of Anesthesiology, Univer- the airway, including inadequate ventilation, esophageal
sity of Michigan Med ical School, Ann Arbor, MI 48109-5861. intubation, and failure to intubate the trachea.
91
One of the m ost critical and potentially d angerous por- cheal intu bation. Many p atients d o not need tracheal intu -
tions of an op eration occu rs at ind uction of, and em ergence bation and m echanical ventilation d u ring GA and place-
from, general anesthesia (GA). Du ring ind u ction of GA, the m ent of a laryngotracheal m ask airw ay (LMA) is su fficient.
anesthetist transitions the patient from consciou s and If tracheal intu bation is requ ired , then there are alternatives
sp ontaneou sly breathing to u nconsciou s and apneic. As a to d irect laryngoscop y u nd er anesthesia. Aw ake intu bation
patient em erges from anesthesia, he or she passes throu gh u sing fiberop tic techniqu e, retrograd e intu bation, or su rgi-
several stages of anesthesia, each of w hich has certain cal tracheostom y are alternative m ethod s available for
implications for m anagem ent of the airw ay. Em ergence p atients w ho are d ifficu lt to ventilate, d ifficu lt to intubate,
from anesthesia is not an all-or-none p henom enon and or both (3,7–9).
prop er tim ing of end otracheal extubation is critical to A d ifficult airw ay is d efined as a clinical situation w here
avoid airw ay obstru ction, aspiration, and hypoxem ia. The an anesthesiologist exp eriences d ifficu lty w ith face m ask
attention of the entire op erating room team shou ld be ventilation of the u p p er airw ay, d ifficu lty w ith tracheal
focused on the p atient, the anesthetist, and his or her assis- intu bation, or both. If it is d ifficu lt or im p ossible to visu al-
tant d u ring these tw o p hases of GA. Potentially life- ize the glottis d esp ite p rop er p ositioning of the head and
threatening p roblem s can d evelop quickly, in w hich case, neck, then laryngoscop y is d ifficu lt. Difficu lty w ith an air-
the anesthetist w ill requ ire rapid , com petent assistance. w ay m ay be anticipated w hen preoperative evalu ation
Em ergent cricothyrotom y m ay be necessary and the su r- reveals a history of, or p hysical exam su ggestive of, d iffi-
geon, regard less of his or her specialty, m ust be p repared to cu lt intu bation. While a nu m ber of very com p lex clinical
perform this life-saving technique on a m om ent’s notice. and rad iograp hic factors that su ggest p otential d ifficulty
Oral intu bation w ith an end otracheal tube (ETT) is u su - w ith laryngoscop y and intu bation have been d escribed ,
ally perform ed after ind u ction of anesthesia w ith a short- m ost anesthesiologists rely on a m ore straightforw ard
acting intravenou s (IV) anesthetic like thiopental or exam ination com bined w ith clinical exp erience. Factors
prop ofol. Alternatively, anesthesia can be ind uced by su ggesting d ifficu lty inclu d e a short m u scu lar neck, fu ll set
inhalation of nitrou s oxid e and stead ily higher concentra- of teeth, reced ing low er jaw, high arched p alate, lim ited
tions of a volatile anesthetic. Mask ventilation is estab- m ou th op ening, lim ited cervical extension, chin-to-thyroid
lished and anesthesia m aintained w ith inhaled anesthetic cartilage d istance of less than 7 cm , and a Mallam p ati score
su ch as isoflu rane. Muscle relaxants facilitate intu bation by of 3 or 4 (Table 12.1) (4). The Mallam p ati test classifies the
ablating reflexive resistance to laryngoscop y and intu ba- ability to see the fau cial p illars and u vu la w hen the patient
tion. Su ccessfu l d irect laryngoscopy and intu bation then op ens his or her m ou th as w id e as p ossible (10). When
d ep end s on p atient characteristics inclu d ing ad equ ate com bined , the latter tw o criteria have a sp ecificity of
m outh op ening, su fficient pharyngeal space, com p liant alm ost 98% (11,12). At other tim es, d ifficu lty is unanticipated
su bmand ibu lar tissue, and u nim paired atlantooccip ital because there are no p red isposing factors su ggesting d iffi-
extension. If any one or m ore of these basic characteristics cu lty and intu bation is exp ected to be u ncom p licated . The
are abnorm al then visu alization and intu bation m ay be latter situ ation can be esp ecially p roblematic if it is d ifficu lt
d ifficu lt (3,4). or im p ossible to ventilate the p atient by m ask after ind u c-
Ind u ction of anesthesia, laryngoscopy, and tracheal tion of anesthesia. The Am erican Society of Anesthesiolo-
intubation is very stim u lating and can be associated w ith gists Task Force on Managem ent of the Difficu lt Airw ay
m arked hem od ynam ic changes, w hich can be of concern in has d evelop ed and refined p ractice gu id elines for m anag-
certain su bsets of p atients, su ch as those w ith ischem ic ing these variou s clinical situ ations (8). The guid elines
heart d isease, acu te aortic synd rom e or intracranial inclu d e an algorithm , w hich is rep rod u ced in Figu re 12.1.
aneu rysm . The hem od ynam ic response d epend s on a vari- The practice guid elines and algorithm d escribe a set of
ety of factors, inclu d ing the method of ind uction, the tech- strategies that m ay be executed in the acute situ ation of
nique u sed for intu bation, and the com bination of u nfold ing d ifficu lty. A recent su rvey of anesthesiologists
anesthetic m ed ications u sed to attenu ate these resp onses. revealed that w hen confronted w ith a d ifficu lt airw ay sce-
For examp le, a stu d y comp aring several ind uction regi- nario, m ost chose to ap p roach the airw ay w ith d irect laryn-
m ens d em onstrated that ind u ction w ith thiop ental alone goscop y or fiberop tic techniqu es (13). All other m ethod s
resulted in u nd esirable hem od ynam ics (tachycard ia and w ere m u ch less frequ ently u sed .
hypertension) and elevations of p lasm a catecholam ines The lip s, teeth, tongu e, bu ccal m u cosa, p alate and per-
w hile thiop ental su p plem ented w ith fentanyl (6 g/ kg) m anent d ental ap p liances can be inju red or d am aged d u r-
attenu ated this resp onse (5). Barak et al. com pared tw o ing laryngoscop y or by any one of a nu m ber of foreign
m ethod s of intu bating anesthetized patients, d irect laryn- objects (oral airw ay, bite block, ETT, or laryngeal m ask air-
goscop y and fiberop tic bronchoscopy, and found that both w ay) p laced in the airw ay d u ring GA. Inju ry to the lips,
m ethod s resu lted in sim ilar hem od ynam ic changes (6). both u p p er and low er, is com m on d u ring intu bation using
H eart rate and blood p ressu re increased after intu bation a laryngoscop e, esp ecially w hen p erform ed by inexperi-
but not d uring laryngoscopy or bronchoscopy. enced p ractitioners. Seriou s consequ ences are rare and
There are alternatives to oral intubation w ith an ETT. the inju ry can be treated conservatively. Dental inju ry
For exam p le, certain operations are best served by nasotra- requ iring rep air or extraction occu rs in ap p roxim ately 1 in
Chapter 12 • Anesthesia Complications 93
Table 1 2 .1 Com p on en t s of t h e p r eop era t ive a ir way p hysica l exa m in a t ion

Airway Examination Component Nonreassuring Findings
Length of upper incisors Relatively long
Relation of maxillary and mandibular incisors during normal jaw closure Prominent “overbite” (maxillary incisors anterior to mandibular incisors)
Relation of maxillary and mandibular incisors during voluntary protrusion Patient cannot bring mandibular incisors anterior to (mandible in front of)
of mandible maxillary incisors
Interincisor distance (mouth opening) Less than 3 cm
Visibility of uvula Not visible when tongue is protruded with patient in sitting position
(e.g., Mallampati class greater than II)
Shape of palate Highly arched or very narrow
Compliance of mandibular space Stiff, indurated, occupied by mass, or nonresilient
Thyromental distance Less than three ordinary finger breadths
Length of neck Short
Thickness of neck Thick
Range of motion of head and neck Patient cannot touch tip of chin to chest or cannot extend neck
Adapted from Society of Anesthesiologists Task Force on Management of the Difficult Airway. Practice guidelines for management of the difficult airway: an updated report by
the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology2003;98(5):1269–1277.
4500 cases and u sually involves the upp er incisors (14). orotracheal intu bation w ith m anu al in-line cervical sp ine
Preexisting poor d entition and d ifficu lty intu bating the stabilization, bu t the valu e of this and other stabilization
p atient increases the risk of d am age to the teeth. Tongu e maneu vers is not p roven (16). In a stu d y u sing cad avers,
trau m a and sw elling can be the resu lt of prolonged com - Lennarson et al. d em onstrated that m anu al in-line stabi-
p ression by an ETT oral airw ay, or surgical retractor, or it lization d id not p revent motion of the inju red or intact cer-
can be the resu lt of p ositioning the head in extreme flexion, vical sp ine d u ring laryngoscop y and intu bation (16). Still,
esp ecially w hen the p atient is p ositioned head -u p for p os- cu rrent teaching and gu id elines ad vocate that all effort
terior neu rosu rgical proced u res. In contrast to other oral shou ld be m ad e to m inim ize cervical sp ine m otion d u ring
and d ental inju ries, injuries to the tem porom and ibu lar laryngoscop y and intu bation. With carefu l techniqu e, the
joint alm ost alw ays occur in young, female, ASA p hysical risk of cau sing or w orsening a sp inal cord inju ry is low,
statu s 1 and 2 p atients although patients w ith facial skeletal regard less of the techniqu e u sed to intu bate the p atient.
abnorm alities are also at risk (Table 12.2). The d islocated Du ring elective intu bation, the p atient’s anatom ic configu -
tem porom and ibular joint shou ld be red u ced im m ed iately ration or halo cervical stabilization m ay su ggest d ifficu lty
after the cond ition is recognized . w ith d irect laryngoscop y and in these cases alternate tech-
The top ics of esop hageal inju ry and laryngotracheal niqu es for intu bation (fiberoptic) m ay be necessary.
trau m a are covered in a recent review (15). A variety of cond itions are associated w ith potential
Im p rop er m anip u lation of an u nstable cervical sp ine im m obility and / or instability of the cervical sp ine, inclu d -
m ay cau se fractu re or su blu xation of the osseou s com p o- ing Dow n’s synd rom e, rheu m atoid arthritis, ankylosing
nents of the sp ine resu lting in cord com p ression and neu rosp ond ylitis and trau m a (see Table 12.3). H igh-risk rheum a-
logic inju ry. Establishing a m ask airw ay for ventilation, and toid p atients are those w ith neck sym p tom s, ad vanced age,
p ositioning the head and neck for intubation, involves longstand ing d isease, erosive d isease, and su bcu taneous
p ositioning the head and neck in the sniffing position by nod u les. These p atients shou ld have lateral cervical spine
flexing the low er cervical sp ine and extend ing the occip ital x-rays p erform ed in neu tral p osition, flexion, and exten-
atlantoaxial com p lex. The m ajority of m otion d u ring laryn- sion p rior to GA.
goscop y and intu bation in anesthetized , paralyzed p atients N asal intu bation is a safe and useful technique w hen
w ith intact cervical sp ines occurs at the occipu t-C1 ju nction p erform ed by exp erienced p ersons (Table 12.4). The m ost
(16). Theoretically, a person perform ing tracheal intu bation com m on com p lication is ep istaxis, w hich is u su ally self-
could create or exacerbate a spinal cord inju ry, esp ecially lim ited but can be serious in anticoagu lated patients or
d u ring d ifficu lt laryngoscopy, but there are very little d ata those p atients w ith a coagu lop athy. N asal bruising is also
to su p p ort this occurrence (17). qu ite com m on, bu t frank m u cosal tears, lacerations, and
In the acu te setting of a know n or su sp ected sp inal cord false su bm u cosal p assage are u ncom m on. N asal intu bation
inju ry and a com prom ised airw ay, establishing an airw ay is potentially very hazard ou s in certain cond itions su ch as
and su p p orting breathing takes preced ence (17). Cu rrent facial trau ma and skull fracture w here inad vertent intuba-
Ad vanced Trau m a Life Su pport gu id elines recom m end tions of the craniu m and orbit have been rep orted (18). The
FIGURE 12.1. The ASA Difficult Airway Algo- Awake intubatio n

(a)
rithm. Other options include (but are not lim-
ited to) surgery utilizing face mask or LMA
anesthesia, local anesthesia infiltration or
regional nerve blockade. Pursuit of these Airway a pproa che d by noninva s ive intuba tion Inva s ive a irway a cce s s (b)*
options usually implies that mask ventilation will
not be problematic. Therefore, these options
may be of limited value if this step in the algo- S ucce e d* FAIL
rithm has been reached in the Emergency Path-
way. (b)Invasive airway access includes surgical
or percutaneous tracheostomy or cricothyro- Ca nce l ca s e Cons ide r fe a s ibility Inva s ive a irway a cce s s (b)*
tomy. (c)Alternative noninvasive approaches to of othe r options (a )
difficult intubation include (but are not limited A
to): use of different laryngoscope blades. LMA
as an intubation conduit (with or without Intubatio n atte mpts afte r induc tio n o f g e ne ral ane s the s ia
fiberoptic guidance), fiberoptic intubation, intu-
bating stylet or tube changer, light wand, retro-
grade intubation, and blind oral or nasal Initia l intuba tion a tte mpts s ucce s s ful* Initia l intuba tion a tte mpts UNS UCCES S FUL
intubation. (d)Consider re-preparation of the
patient for awake intubation or canceling sur- From this point onwa rds cons ide r:
gery. (e)Options for emergency noninvasive air- 1. Ca lling for he lp
way ventilation include (but are not limited to): Fa ce ma s k ve ntila tion a de qua te 2. Re turning to s ponta ne ous
rigid bronchoscope, esophageal-tracheal Com- ve ntila tion
bitube ventilation, or transtracheal jet ventila- 3. Awa ke ning the pa tie nt
tion. (Adapted from Society of Anesthesiologists
Task Force on Management of the Difficult Air-
way. Practice guidelines for management of the Fa ce ma s k ve ntila tion not a de qua te
difficult airway: an updated report by the Amer-
ican Society of Anesthesiologists Task Force on
Management of the Difficult Airway. Anesthe- Cons ide r/Atte mpt LMA
siology 2003;98(5):1269–1277.)
No ne me rg e ncy pathway LMA a de qua te * LMA not a de qua te

Ve ntila tion a de qua te, or not fe a s ible
intuba tion uns ucce s s ful
Eme rg e ncy pathway

Ve ntila tion not a de qua te,
intuba tion uns ucce s s ful
Ca ll for he lp
Alte rna tive a pproa che s If both fa ce ma s k
to intuba tion (c) a nd LMA ve ntila tion
be come ina de qua te Eme rge ncy noninva s ive
ve ntila tion (e )
S ucce s s ful FAIL a fte r S ucce s s ful FAIL

intuba tion* multiple ve ntila tion*
a tte mpts
Eme rge ncy inva s ive
a irway a cce s s (b)*
Inva s ive a irway Cons ide r fe a s ibility Awa ke n pa tie nt(d)
a cce s s (b)* of othe r options (a )
B
*Confirm ve ntila tion, tra che a l intuba tion, or LMA pla ce me nt with exha le d CO 2 .
techniqu e is generally contraind icated in these situ ations assessm ent, p rep aration of the nasal m u cosa w ith lu bricat-
u nless absolu tely necessary and perform ed carefully w ith ing jellies and vasoconstrictors, selection of a sup ple,
the assistance of fiberoptic bronchoscopy. u ncu ffed tu be, and carefu l insertion of a w ell-lu bricated
The techniqu e of nasal intu bation has been recently and tu be. Once the tu be is beyond the nasop harynx, it can be
thorou ghly review ed (19). The authors em phasize several gu id ed into the trachea either blind ly, u nd er d irect laryn-
aspects of the techniqu e in ord er to red u ce the incid ence of goscop ic visu alization, or w ith the assistance of fiberoptic
com m on com p lications, includ ing careful p reoperative bronchoscop y. Once in p lace, the tu be m u st be carefully
Table 1 2 .2 ASA p hysica l cla ssifi ca t ion Table 1 2 .4 In d ica t ion s for n a sa l in t u ba t ion (19)
P1 A normal healthy patient Head and neck surgery Dental surgery
P2 A patient with mild systemic disease Intraoral and oropharyngeal surgery
Rigid laryngoscopy and microlaryngeal surgery
P3 A patient with severe systemic disease Jaws wired or fixed shut at end of operation
P4 A patient with severe systemic disease that is a constant General indications Intra-oral pathology including obstructive
threat to life lesions
P5 A moribund patient who is not expected to survive without Cervical spine instability or degenerative spine
the operation disease
P6 A declared brain-dead patient whose organs are being Obstructive sleep apnea
removed for donor purposes
secured to prevent inad vertent extubation and to avoid chest exp ansion d u ring inhalation) shou ld be obvious. An
p ressu re on the nasal ala, w hich can cau se tissue ischem ia otherw ise norm ally p laced ETT m ay “m igrate” into a
or necrosis. bronchu s for a variety of reasons. A steep Trend elenbu rg
Inad vertent intu bation of the esop hagu s can occu r p osition can force the abd omen, d iap hragm , and chest
w hen d irect visualization of the glottis is d ifficu lt bu t it can organs to m ove cep halad tow ard the ETT. Flexion of the
also occu r w hen visu alization is id eal. Esophageal intu ba- head w ill m ove the ETT d eep er into the airw ay (20).
tion and ventilation of the stom ach is of little consequ ence, An end obronchial inju ry can be the resu lt of m isp laced
as long as the condition is rapidly recognized and corrected. The ETTs, tube guid es, tube changers or properly placed double-
p resence of carbon d ioxid e (CO 2) in exhaled gases can be lumen ETTs. Severe end obronchial injury almost alw ays
d etected by end -tid al CO 2 m onitoring and is the m ost accu - resu lts in pneu m othorax, w hich can rapid ly p rogress to ten-
rate and reliable m ethod of confirm ing p rop er p lacem ent sion p neu m othorax in p atients receiving p ositive p ressu re
of the ETT in the trachea. Clinical signs su ch as bilateral ventilation (18).
breath sou nd s, cond ensation in the ETT, chest w all m ove- The laryngeal mask airw ay is an invaluable tool for
m ent, and absence of gastric sou nd s cannot be relied u p on m anagem ent of the airw ay in elective op erations and cer-
for confirm ation becau se they are all p otentially m islead - tain em ergency situ ations. In fact, the laryngeal m ask air-
ing. If the esop hagus is intubated , the ETT shou ld be left in w ay has em erged as a very im p ortant com p onent of the
place u ntil the trachea is correctly intu bated (12). Leaving d ifficu lt airw ay algorithm and is frequ ently su ccessfu l in
the ETT in the esophagus help s p rotect the trachea from salvaging ventilation in p atients w ho are d ifficu lt to intu -
regu rgitated gastric contents and helps id entify the proper bate and d ifficu lt to ventilate by face m ask (21,22). While
orifice for intu bation. m any anesthesiologists and su rgeons regard p lacem ent of
Perhaps one of the m ost com m on causes of intra-opera- an LMA as “less invasive” and less trau m atic than d irect
tive arterial oxygen d esaturation in an otherw ise healthy laryngoscop y follow ed by end otracheal intu bation, use of
patient is bronchial intu bation. An ETT that is p laced too the LMA is not w ithou t com p lication. In one review of air-
d eep ly w ill m ost likely intu bate the right m ainstem w ay com p lications in p ed iatric p atients, the rate of com pli-
bronchu s, resu lting in hypoventilation of the left lu ng. cations w as actu ally higher w ith the LMA than w ith
Clinical evid ence of this phenom enon (u nilateral d ecreased end otracheal intu bation bu t they w ere clinically less signif-
breath sou nd s, increased inflation pressu re, asym m etric icant (23). Com p lications w ith the LMA can be broad ly
d ivid ed into p haryngolaryngeal and neu rovascu lar com -
p lications.
One d isad vantage of the LMA is that it cannot provid e
Table 1 2 .3 Con d it ion s a ssocia t ed w it h com p lete p rotection against asp iration of gastric contents
a t la n t oa xia l su blu xa t ion (230) or secretions. The incid ence of su bclinical asp iration m ay
be as high as 25% bu t the incid ence of seriou s asp iration
Congenital Down syndrome
ap p ears to be m u ch low er (18). The occu rrence of m ild
Odontoid anomalies
Mucopolysaccharidoses
hoarseness (12%), sore throat (10%), and d ysp hagia (4%) all
ap p ear to be related to m alp osition or excess cu ff pressu re.
Acquired Still’s disease Pharyngeal abrasions and u lcers of the soft palate and
Ankylosing spondylitis
u vu la are u su ally associated w ith d ifficu lt placem ent of the
Psoriatic arthritis
d evice.
Enteropathic arthritis (Crohn’s disease, ulcerative colitis)
Reiter’s syndrome A variety of nerve inju ries have been rep orted w ith u se
Trauma (odontoid fracture, ligamentous disruption) of the LMA, inclu d ing lingu al, recu rrent laryngeal, and
hyp oglossal nerve d am age (18). In general, serious nerve
inju ries seem to be related to neu rovascu lar com p ression d evelop s, then the p recip itating irritating m aterial shou ld
from excess p ressu re on pharyngeal stru ctures. Excess be rem oved w hile ad m inistering 100% oxygen by positive
p ressu re on ad jacent structures m ay be a result of m alp osi- p ressu re ventilation. Occasionally, it is necessary to d eepen
tion of the d evice, or excessive cu ff inflation, especially in the anesthesia or ad m inister a sm all d ose of su ccinyl-
the presence of nitrou s oxid e. Thu s, some inju ries m ay be choline to “break” the spasm and som etim es reintubation
avoid ed by m onitoring cu ff p ressu re and keeping it at the is required .
low est level that allow s for ad equate gas exchange. In a Pulmonary ed ema may occur after acu te up per airw ay
p rospective, rand omized trial in 200 patients, Seet et al. tract obstruction, in w hich case it is termed N PPE. The pul-
d em onstrated that m aintaining LMA intracu ff p ressu re to monary ed ema occurs w ithin minutes of the onset of airw ay
less than 44 m m H g low ers the incid ence of postop erative obstruction and rad iological find ings d emonstrate perihilar
p haryngolaryngeal com plications. The investigators su g- infiltrate w ith d iffuse pu lm onary ed em a. The p athogenesis
gest that LMA cu ff p ressu res shou ld be m easu red rou tinely of N PPE is multifactorial but the pred ominant mechanism
u sing m anom etry, and d eflating the intracuff p ressu re to is generation of m arked ly negative intrap leu ral pressu res
less than 44 m m H g shou ld be recom m end ed as anesthetic by forceful inspiration against an obstructed airw ay (28).
best practice (24). Malposition, on the other hand , m ay be The d ifferential d iagnosis includ es acid aspiration, card io-
hard to recognize becau se ad equ ate ventilation m ay be genic pu lm onary ed em a, and iatrogenic volume overload ,
p ossible even w hen the d evice is not p roperly seated . The bu t the temporal relation of pu lmonary ed ema to clinically
only w ay to accu rately confirm prop er positioning is w ith obviou s airw ay obstru ction in an otherw ise healthy patient
fiberoptic exam ination of the glottis from w ithin the LMA strongly suggests N PPE. The most frequent cause of airw ay
bu t fiberop tic confirm ation is not perform ed rou tinely (18). obstruction lead ing to N PPE is postextubation laryn-
As m entioned earlier, extu bation is another critical gospasm but acute airw ay obstru ction occu rring anytime
p hase (stage) in the cond uct of GA and it can be com pli- d uring management of the airw ay can be follow ed by
cated by a variety of events inclu d ing, bu t not lim ited to, N PPE (29). The first p riority in m anaging N PPE is re-
aspiration, laryngospasm, negative p ressu re p ulmonary establishing a patent airw ay and assu ring ad equ ate oxy-
ed em a (N PPE), and airw ay com pression. genation. Most cases resolve spontaneously w ithout further
Tracheom alacia lead ing to tracheal collap se m ay p ro- complication although some patients may require reintuba-
d u ce up p er airw ay obstru ction follow ing extu bation. Tra- tion follow ed by a brief period of mechanical ventilation
cheom alacia is u su ally second ary to thyroid goiter w here w ith positive end -expiratory pressure (PEEP) (28).
the cartilaginous rings of the trachea m ay be w eakened or
d estroyed . In these cases, rem oval of the goiter fu rther
com p rom ises the stru ctu ral integrity of the trachea and col-
■ GENERAL ANESTHESIA
lapse can occu r shortly after tracheal extubation. Reintu ba- The term “anesthesia” signifies insensibility to surgical
tion is requ ired . Su bsequent treatm ent options inclu d e p ain. Other com p onents of anesthesia inclu d e am nesia,
tracheostom y, tracheoplasty, or p lacem ent of external or hyp nosis (u nconsciou sness), m u scle relaxation, inhibition
internal tracheal su p port (25). of m ovem ent, and blu nting of the au tonom ic response in
Laryngosp asm is norm ally a p rotective reflex w here the resp onse to noxiou s stim u li. A variety of d ru gs provid e
glottis is occlu d ed by contraction of the intrinsic laryngeal som e or all of these com p onents of anesthesia. The gam u t
m u scles. Usu ally laryngospasm occu rs to p revent asp ira- of p harm acologic agents u sed in GA has been thoroughly
tion of foreign m aterial into the trachea and is m ed iated by review ed elsew here (30). Recent d evelop m ent of anesthetic
the vagu s nerve. The reflex can occu r in response to the m ed ications has focu sed on those com p ou nd s w ith a rap id
p resence of airw ay irritants (secretions, blood , ETT) d u ring onset and recovery w ith minim al sid e effects and d ru g-
a light p lane of anesthesia. During this light plane of anes- d ru g interactions.
thesia, referred to as stage II, the level of anesthesia is insu f- A fu nd am ental p rem ise of GA is that the state of u ncon-
ficient to prevent the laryngospasm reflex bu t is too d eep to sciou sness and u nresponsiveness prod uced by anesthetics
allow a norm al cou gh reflex (26). If laryngosp asm occu rs is reversible and that the brain and sp inal cord are neu ro-
after tracheal extu bation, then u pper airw ay obstru ction p hysiologically the sam e before and after anesthesia.
m ay ensu e. Laryngosp asm is the m ost com m on cau se of Recent stu d ies have qu estioned the com p lete reversibility
u pper airw ay obstru ction after tracheal extu bation and is of anesthesia, su ggesting that anesthesia and / or anesthet-
esp ecially frequ ent in child ren after u p p er airw ay su rgery ics m ay have long-lasting d etrim ental or toxic effects. This
(27). Id eally, all attem pts shou ld be m ad e to avoid p recip i- concep t w ill be d iscu ssed below.
tating laryngospasm by rem oving potential irritants by
thorou gh su ctioning of the mouth and throat prior to extu -
bation. Extu bation should occu r w hile the p atient is d eep ly
■ Potent inhaled anesthetics
anesthetized or after the patient has passed ou t of stage II Potent inhaled anesthetics (PIAs) are halogenated hyd ro-
anesthesia and is follow ing simp le com m and s. App lying carbons and ether com p ou nd s that rend er p atients am nes-
p ositive p ressu re d uring extu bation can clear potentially tic and im m obile to noxiou s stim u li. Cu rrent theories on
irritating m aterial from the cord s. If laryngosp asm the m echanism s of action of the PIAs have been recently
review ed (31). Their am nestic and hypnotic affects are hep atic failu re w ith high m ortality. Even in 1970, an allergic
m ed iated in the brain w hile their action to inhibit m ove- typ e reaction w as hyp othesized d esp ite the relatively inert
m ent in resp onse to noxiou s stim u li is second ary to d ep res- natu re of halothane. H ep atotoxicity resu lting in fulm inant
sion of sp inal cord function. There are separate m olecu lar liver failu re involves a hum oral response that is d irected
targets for each of these actions. While the volatile anes- tow ard hep atocyte cytochrom es that have been altered by
thetics can cau se card iopu lm onary d epression and d eath at an oxid ative reactive m etabolite of halothane (40,41).
concentrations near those that p rod u ce d eep anesthesia, When the bod y m etabolizes m ethoxyflu rane, enflu rane,
this is extremely rare, largely due to reliable gas delivery sys- and sevoflu rane, flu orid e ions are p rod u ced , w hich m ay be
tems, agent analyzers, and hemodynamic monitors. Rather, toxic to the kid neys resu lting in im p airm ent of concentrat-
ad verse sid e effects are usually mild and includ e nau sea, ing ability and acu te renal failu re. The m etabolism of
vom iting, and d eliriu m . halothane, isoflu rane, and d esflu rane d oes not prod u ce sig-
The clinical effects of inhaled anesthetics, ranging from nificant levels of flu orid e ions and there is little potential
euphoria to profound cardiopulmonary depression, d epend for nep hrotoxicity w ith these com p ou nd s (41).
on the inhaled concentration. A nu mber of scales are u sed to Sevoflu rane reacts w ith the m aterial in CO 2 absorbers to
assess anesthetic potency and they are based on the relation form a vinyl chlorid e called Com p ou nd A, w hich prod uces
betw een alveolar concentration and a certain behavioral renal tu bu lar necrosis in laboratory anim als (41). The
end point. The med ian alveolar concentration (MAC) is one m ajority of hu m an stu d ies show that there is no clinical
of these scales and is d efined as the med ian end -tid al con- d egrad ation in renal fu nction even after p rolonged exp o-
centration of inhaled anesthetic that ablates movem ent in su re to low -flow sevoflu rane anesthesia (42,43). In patients
response to surgical incision in 50% of the test p opu lation. w ith im p aired renal fu nction, it w ou ld seem pru d ent to
All of the volatile anesthetics d ecrease blood pressu re in lim it exposu re to sevoflu rane and use high fresh gas flow
a d ose-d ep end ent m anner and all are m yocard ial d ep res- rates, w hich w ill “w ash ou t” the com p ou nd from the anes-
sants. The effect of halothane and enflurane is greater than thesia breathing circu it.
isoflu rane, sevoflurane, and d esflu rane in this regard . PIAs and nitrou s oxid e are know n triggering agents
H alothane sensitizes the myocard iu m to the arrhythm o- for malignant hyp ertherm ia. Ep inep hrine, beta-ad renergic
genic effects of epinephrine. Isoflurane and d esflu rane recep tor agonists, and theop hylline can cau se arrhythm ias
d ecrease blood p ressu re and p erip heral vascu lar resistance in the p resence of halothane. The m yocard ial d ep ressant
w hile increasing heart rate. Anim al stu d ies su ggest that activity of inhaled anesthetics is increased in the presence
isoflu rane p rom otes “coronary steal” by d ilating nond is- of beta-blockers and calciu m channel blockers.
eased coronary vessels and d iverting blood flow to normal
areas aw ay from ischem ic areas (32). Clinically, the effect is
not ap p arent and , if factors affecting m yocard ial oxygen
■ Nitrous oxide
consu m p tion are controlled , isoflurane anesthesia d oes not N itrous oxid e is a relatively insoluble gas that is prim arily
cau se a greater incid ence of ischemia than any other tech- u sed to sup plement the PIAs in GA. It is used alone for
niqu e (33–35). In fact, there is su bstantial evid ence that analgesia in labor and ou tpatient p roced ures such as flexi-
isoflu rane actu ally protects the myocard ium , effectively ble sigmoid oscop y, colonoscop y, and d ental proced ures
lim iting infarct size and im p roving fu nctional recovery fol- (44,45). The primary d anger in using nitrou s oxid e is hypoxia
low ing m yocard ial ischem ia throu gh a m echanism sim ilar that resu lts from either u sing excess am ounts of nitrous
to ischem ic p recond itioning (36,37). oxid e or throu gh d iffu sion. Du ring recovery from anesthe-
PIAs are resp iratory d epressants and d epress the nor- sia u sing nitrous oxid e, large am ou nts of the gas exit the
m al resp onse to hyp ercarbia in a d ose-d ep end ent m anner. blood and “flood ” the alveoli, d isplacing alveolar oxygen
The PIAs irritate the airw ays and m ay prod uce coughing or and CO 2. The patient can become hypoxic if sup plemental
laryngosp asm d u ring inhalation ind u ction of GA. Sevoflu - oxygen is not provid ed along w ith ad equ ate ventilatory
rane and halothane are the least irritating w hile d esflu rane sup port. The hypoxic ventilatory d rive is blu nted .
is the m ost irritating. N itrou s oxid e u su ally p rod u ces m ild sym p athetic stim -
In a d iscu ssion of halothane-associated liver failu re u lation w hen u sed w ith the PIAs but it can cause profou nd
from 1970, halothane is regard ed as close to an id eal anes- card iovascu lar d ep ression w hen u sed in an anesthetic tech-
thetic agent, d espite m any reports of halothane-ind u ced niqu e p rim arily based on op ioid s. It m ay also cau se
hep atitis (38). Tod ay, this assessm ent is not valid becau se m yocard ial d ep ression and hyp otension in p atients w ith
other agents are available that have a m uch better m argin coronary artery d isease (46). N itrou s oxid e raises p ul-
of safety. H alothane-associated liver d am age p resents as m onary vascu lar resistance and m ay increase p u lm onary
one of tw o clinical synd rom es (39). Mild hep atic d am age, artery p ressu re in p atients w ith p u lm onary hyp ertension.
m od erately increased transam inase levels, occasional tran- N itrou s oxid e inactivates vitam in B12, w hich is an
sient jau nd ice, and low m orbid ity characterize the first syn- im p ortant com p onent of tw o biochem ical reactions. In the
d rom e, w hich m ay have an incid ence as high as 20%. The first reaction, vitam in B12 acts as a cofactor in the form ation
second synd rom e is very rare, occu rs after repeated exp o- of m eth ionin e, w h ich is essen tial to DN A syn th esis an d
sure to halothane, and is characterized by fu lm inant to the m ain tenan ce of the m yelin sheath in nerves. In the
second reaction, a form of vitam in B12 fu nctions as a cofac- d elivery of gas to the p atient. Thu s, the gas d elivery system
tor in a reaction that form s su ccinyl coenzym e A, w hich is in the anesthesia m achine serves a critical function in d eliv-
im p ortant for lip id and carbohyd rate synthesis via the ering oxygen and anesthetic gases to the p atient w hile also
Krebs cycle. Patients can d evelop m egaloblastic anem ia, p rovid ing ad equ ate ventilation and CO 2 rem oval.
bone m arrow d ep ression, and neurologic problem s after Serious patient injuries, including death and brain injury,
either prolonged exposure to or chronic inhalation of have resulted from misuse or failure of anesthesia gas d eliv-
nitrou s oxid e (47,48). Persons w ho have vitam in B12 d efi- ery equipment. Other potential injuries include aw areness,
ciency from any cau se, inclu d ing pernicious anem ia, term i- card iovascular collapse, d elayed recovery, and pneumotho-
nal ileu m resection, or su btotal gastrectom y, are especially rax. In a stud y of closed claims, the breathing circuit w as the
at risk of seriou s neu rological d eterioration even after a sin- most comm on source of injury follow ed by the vaporizers,
gle anesthetic w ith nitrou s oxid e. N eu rological m anifesta- ventilator, and the gas supply tank or line (55). Misconnect
tions are sim ilar to vitam in B12 d eficiency and m ay be and disconnect of the breathing circuit were the most fre-
reversed by vitam in B12 therapy (47). Patients w ho inten- quent initiating events. The tw o most common sites of dis-
tionally abu se the gas are also at risk of anem ia and neu ro- connect w ere betw een the ETT and the circuit, and the
logic d isease. N itrou s oxid e exposure is an occu pational ventilator and the breathing circuit. Half of the cases
hazard to op erating room p ersonnel bu t the exact extent of involved inad equate oxygenation as a result of d isconnects,
the risk is not w ell established (49). oxygen supply errors, and failures to turn on the ventilator.
N itrou s oxid e d iffu ses into gas filled sp aces in the bod y Misuse of equipment, d efined as fault or error associated
m ore qu ickly than nitrogen d iffuses ou t. Thu s, it can cau se w ith the preparation, maintenance, or d eployment of a med -
expansion of these sp aces and cavities. Anim al stu d ies p erical d evice, w as much more frequent than equipment failure.
form ed 40 years ago d em onstrated that anesthesia w ith Contem p orary m onitoring gu id elines now m and ate the
nitrous oxid e caused expansion of air pockets w ithin the u se of d evices to assure ad equate oxygenation and ventila-
pleural sp ace (50). Bow el d istension, tension pneum otho- tion. Som e of the cases inclu d ed in the analysis of closed
rax, blind ness after vitrectom y, venous air em bolism , and claim s occu rred w ell before the w id espread ad op tion of
hearing loss have all been reported to occu r d u ring, and p u lse oxim etry and end -tid al CO 2 d etection and 53% of
ow ing to, anesthesia w ith nitrous oxid e (51–53). Interest- claim s w ere ju d ged to be p reventable if p u lse oxim etry,
ingly, there is very little literature to su pport the contention cap nograp hy, or both had been u sed (55). Therefore, m ini-
that nitrou s oxid e d efinitely cau ses clinically significant m al m onitoring shou ld red u ce the incid ence of these
bow el d istention. In fact, one rand om ized trial com p aring events, if ap p rop riately ap p lied .
op erative cond itions w ith and w ithou t nitrou s oxid e for
laparoscopic cholecystectom y failed to d em onstrate any ■ Medications
d etectable d ifference (54).
Intravenous Anesthetics, Sedatives
The id eal IV anesthetic shou ld p rovid e hyp nosis, am nesia,
■ Anesthesia delivery systems and analgesia w ith rap id onset, rap id elim ination w ith
The anesthesia m achine consists of several com ponents m inim al or no sid e effects. Unfortu nately, an id eal IV anes-
that are specified in the current anesthesia gas m achine thetic d oes not exist bu t several m ed ications play an im por-
(w orkstation) stand ard ASTM F1850 prom ulgated by the tant role as ad ju ncts in balanced anesthesia. Several of the
Am erican Society for Testing and Materials. At a m inim u m , IV anesthetics are also u sed at low er d oses for short-term
the m achine fu nctions as a gas d elivery system by provid - or long-term sed ation.
ing a m ethod of m etering and d elivering oxygen, d osing The barbitu rates (thiop ental, m ethohexital, and thiamy-
and d elivering PIAs, and d elivering controlled m echanical lal) have a rap id and short action. They are som e of the
ventilation. In ad d ition, the m od ern m achine incorp orates stand ard d ru gs u sed to ind u ce anesthesia. They enhance
a w id e variety of safety m echanism s, m onitors, and alarm s and m im ic the action of gam m a am ino bu tyric acid
that are d esigned to alert the anesthetist to m alfunction or (GABA) at the GABA recep tor in the central nervou s sys-
operation that is ou t norm al param eters. A variety of p hys- tem (CN S). The p rim ary card iovascu lar effect is venod ila-
iologic monitors, com puters, cabling, d ru g d elivery sys- tion and p ooling of blood in the p erip hery. Blood pressure
tem s, su ction d evices, and other ad ju vants m ay be attached and card iac ou tp u t can d rop d u e to d ecreased venou s
or incorp orated into the m achine (Fig. 12.2). retu rn (56). H yp otension can be severe in p atients w ith
The gas d elivery system controls the flow of oxygen, air, im p aired card iac fu nction, hyp ovolem ia, ad renocortical
and nitrou s oxid e from w all connections or gas cylind ers. insu fficiency, u remia, or sep sis. The barbitu rates are potent
The vaporizers m eter vap or from PIAs and blend the respiratory d epressants; the d egree of resp iratory d ep res-
vapors w ith the fresh gas flow. The fresh gas flow enters the sion d epend s on the d ose and rate of injection and presence
breathing circu it, w hich m ay or m ay not recircu late of other m ed ications. An ind u ction d ose that rend ers a
exhaled gases throu gh a CO 2 scavenging system . Du ring patient unconscious will cause apnea. Smaller doses may
controlled ventilation, a m echanical ventilator controls leave the patient in a light plane of anesthesia and susceptible
FIGURE 12.2. The anesthesia machine. It is almost always located at the head of the operating room table on the patient’s right-hand
side. A modern anesthesia workstation (“machine”) typically includes the following components (letters in parenthesis correspond with
labeled arrows on the photograph).
• Pipeline gas supply (H)—Gases from the hospital medical gas system provide oxygen, nitrous oxide, and air. The machine must pref-
erentially use pipeline gas as long as pipeline pressure is greater than 345 kPa (50 psi).
• Oxygen flush (C)—A high-flow oxygen flush is present, which does not proceed through any vaporizers and provides pure oxygen at
35–75 L/min.
• Flow meters (rotameters) for oxygen, air, and nitrous oxide (B)—The flow meters allow the anesthetist to provide accurate mixtures of
medical gases to the patient. Increasingly, flow meters, which were previously mechanical and pneumatic, are digital, electromagnetic
devices.
• Anesthetic vaporizers (F)—The anesthetic vaporizer is concentration calibrated for a specific agent. It is filled with liquid anesthetic
via a keyed-filler device. The vaporizer accurately adds volatile anesthetic vapor in a precise amount to the fresh gas flow.
• Ventilator (C)—Modern ventilators are capable of providing a number of ventilation modes. The breathing circuit can also be manually
inflated by a handbag.
• Physiological monitors (A)—These systems display, monitor, and record the patient’s heart rate, ECG, noninvasive blood pressure and
oxygen saturation, end-tidal CO2, temperature. In addition, arterial blood pressure, central venous pressure, pulmonary artery pres-
sure, cardiac output, bispectral index, etc., can be displayed and monitored.
• System monitors (B)—A number of other parameters are monitored continuously including the exhaled volume, inflation pressure,
inspired oxygen concentration, the composition of the gases delivered to the patient (and breathed out).
• Breathing circuit (D)—The breathing circuit is commonly a circle system that incorporates one-way valves and a CO2 absorber. The
circle system passes exhaled gas through the CO2 absorber and back into the inspiratory limb allowing for conservation of anesthetic
vapor (gas).
• Suction apparatus
• Anesthesia information system (E)—This optional system provides automated record keeping, rules-based prompts, and access to
other hospital information systems.
Other (safety) features not illustrated
• Reserve gas cylinder(s)—The machine must have at least one reserve gas cylinder of oxygen connected by a pin-indexed (specific)
hanger yoke. Newer machines may only have oxygen reserve cylinders but many other machines have cylinders of nitrous oxide and
air as well.
• Scavenging system—Scavenging systems remove expired anesthetic gases from the operating room. Scavenged gases are usually
vented to the outside atmosphere.
• Alarm systems—There are numerous alarms built into the machine and grouped into high, medium, and low priority. Mandatory alarms
that are automatically enabled include breathing circuit pressure, oxygen concentration, exhaled volume, and/or exhaled CO2. Other
alarms include disconnect, oxygen supply failure, and low inspired oxygen concentration.
• Hypoxic guard system—It protects against less than 21% inspired oxygen if nitrous oxide is in use.
• Pressure gauges, regulators, and “pop-off” valves—These components protect the patient and machine from high pressure.
• Checklist—The machine checklist guides the operator through a series of steps designed to check the machine for proper set up and
function. The checklist may be electronic or on paper, to be filled out manually by the user.
• Digital interface—The digital interface transfers data about the operating parameters of the system to the electronic medical record
and/or diagnostic equipment.
• Battery backup—It is capable of providing several minutes of operation in the absence of electricity from a wall connection.
to laryngosp asm , coughing, or bronchospasm d u ring air- (69–71). In p atients w ith coronary artery d isease, propofol
w ay stim u lation, su ch as p lacem ent of an oral airw ay or can cause card iovascu lar d epression and hypotension.
m ask ventilation. Prop ofol is su p p lied as an aqu eou s em u lsification of soy-
The barbitu rates can cau se seriou s tissu e d am age if bean oil, glycerol, and egg p hosp hatid e and it su pports
the m ed ication extravasates d u rin g IV in jection or is acci- microbial grow th at room tem p eratu re (72). Originally,
d entally injected intra-arterially. Thiobarbiturates ind u ce p rop ofol w as p reservative-free bu t it now com es in form u -
release of histam ine from m ast cells; an urticarial rash on lations that retard m icrobial grow th. Ep id em iologic stu d ies
the u pper bod y and arm s is not u ncomm on bu t tru e ana- have su ggested that p rop ofol, p oor asep tic technique, and
p hylactic reactions are unu su al (57). Patients m ay exp eri- mishand ling of this m ed ication have contribu ted to post-
ence d eliriu m , p rolonged som nolence and recovery, and op erative infections bu t there is consid erable controversy
head ache after their anesthetic esp ecially if they are given over w hether there is a tru e cau sal relationship (73–76). In
high d oses of barbitu rates d u ring short proced u res. Barbi- resp onse to these case rep orts, stu d ies and concerns, the
tu rates can p recip itate acute abd om inal p ain, vom iting, manu factu rer and the FDA cond ucted an extensive ed u ca-
tachycard ia, hyp ertension, fever, confusion, seizu res, tion cam p aign and the p ackage insert w as changed . The
p aralysis, and even d eath in patients w ith variou s typ es of insert now w arns abou t the potential for infection and p ro-
p orphyria (58). In general, barbiturates are contraind icated vid es recom m end ations for p rop er m ethod s to red u ce this
in p atients w ith p orp hyria and there are several alterna- risk (77). Unfortu nately, infectiou s com p lications related
tives available. to p rop ofol continu e to occu r. In 2010, a Las Vegas jury
Benzod iazep ines are a m ainstay in contem p orary anes- aw ard ed p laintiffs a $500 m illion ju d gm ent against the
thesia becau se of their hypnotic and am nestic properties manu factu rers of prop ofol for an alleged ou tbreak of hepa-
com bined w ith a low incid ence of sid e effects. Mid azolam titis C related to im p rop er reu se of single-d ose vials of
is p robably the m ost frequ ently u sed d ru g in the class. p rop ofol across m u ltip le p atients. This ou tbreak w as attrib-
Mid azolam cau ses a m ild d ecrease in blood pressu re, u ted to u nsafe injection practices on the p art of anesthesia
p erip heral vascu lar resistance, and card iac outpu t w hen p ersonnel w ho w ere ad m inistering p rop ofol to patients
u sed alone. When m id azolam is com bined w ith other m ed - u nd ergoing sed ation for end oscop y p roced u res (78,79).
ications, esp ecially the synthetic op ioid s, hypnosis, resp ira- The term “p rop ofol infu sion synd rom e” has been u sed
tory d ep ression, and hypotension can be profou nd (59,60). to d escribe a rare synd rom e of card iac failu re, rhabd om yol-
The synergistic effect of m id azolam and fentanyl or alfen- ysis, severe metabolic acid osis, and renal failu re occu rring
tanil has been exploited for ind u ction of anesthesia in d ay in critically ill child ren and ad u lts receiving high d ose,
surgery (61). Even w hen used alone for conscious sed ation, long-term p rop ofol infu sions (80). It is likely that prop ofol
m id azolam alone can cau se resp iratory d ep ression. im pairs free fatty acid utilization and mitochond rial activ-
Etom id ate is a su bstitu ted im id azole, like ketoconazole, ity lead ing to an im balance betw een energy d em and and
that is u sed as an IV sed ative-hypnotic to ind uce anesthe- u tilization. In som e p atients w ith critical illnesses, propo-
sia. It can cau se p ain on injection, phlebitis, m yoclonic fol, along w ith glu cocorticoid s and catecholam ines, can
m ovem ents, nau sea, vom iting, and ad renocortical su p - lead to necrosis of card iac and skeletal m u scle.
p ression. N au sea and vom iting are especially com m on Ketam ine is a uniqu e IV anesthetic becau se it provid es
(62). A m ajor d isad vantage of etom id ate is its inhibition of sed ation, am nesia, analgesia, and anesthesia. Ketam ine is
cortisol and m ineralocorticoid synthesis in the ad renal classified as an antagonist of the N -m ethyl-D-aspartate
gland s. This w as first noted in the m id -1980s w hen (N MDA) recep tor bu t it also bind s to op ioid recep tors. In
increased m ortality w as rep orted in p atients sed ated w ith vivo, ketam ine increases heart rate, blood p ressu re, and
continu ou s infu sions of etom id ate (63). Both a single d ose p u lm onary artery p ressu re by increasing sym p athetic tone
and continu ou s infu sion of etom id ate inhibit tw o m ito- (81). Ketam ine p rod u ces its sym p athom im etic action
chond rial cytochrom e P-450-d epend ent enzym es, w hich, throu gh d irect stim u lation of CN S stru ctu res. Ad m inistra-
in turn, inhibits ad renal steroid prod uction (64,65). On the tion of ketam ine can resu lt in hyp otension and m yocard ial
other hand , etom id ate is generally associated w ith card io- d ep ression in chronically ill p atients w ith d ep leted cate-
vascu lar stability and preserved blood pressu re d uring cholam ine stores. Airw ay reflexes are u su ally m aintained
ind uction (66). Unfortunately, card iovascu lar stability is bu t obstru ction and ap nea can occu r. Orop haryngeal secre-
not assu red in all p atients (67). tions can be increased . Ketam ine is a p otent cerebral
Prop ofol can cau se pain on injection, cou gh, hiccu p s, vasod ilator that can increase intracranial p ressu re (ICP).
involu ntary skeletal m uscle m ovem ents, and seizu re-like Ketam ine is notoriou s for cau sing p sychic d istu rbances
episod es. Prop ofol cau ses less nausea and vom iting than and em ergence d eliriu m , w hich can occu r in 15% to 30% of
thiopental. Like the barbitu rates, propofol is a resp iratory p atients. These d istu rbances are d escribed as extracorpo-
d ep ressant and cau ses ap nea w ith ind u ction and d ecreased real (ou t-of-bod y) exp eriences, floating sensations, vivid
tid al volum e w ith preserved respiratory rate d u ring m ain- d ream s, and frank d eliriu m (82). Ad m inistering benzod i-
tenance (68). Prop ofol u su ally cau ses a d rop in blood p res- azep ines along w ith ketam ine red u ces the incid ence of
sure d uring ind uction of anesthesia d u e to vasod ilation p ostanesthesia em ergence reactions and ad verse card io-
and d ecreased card iac ou tp ut from m yocard ial d ep ression vascu lar reactions.
Neuromuscular Blocking Agents Som e p atients d o not m etabolize su ccinylcholine nor-

Mu scle relaxation d u ring anesthesia can be accom p lished mally and they have a prolonged response to the d ru g.
w ith a variety of m ethod s and m ed ications. Inhalational Four percent of patients have an abnorm al gene that con-
anesthesia w orks at the level of the spinal cord to inhibit trols the qu antity and qu ality of the enzym e that d egrad es
m ovem ent to noxiou s stim ulation. Local anesthetics are su ccinylcholine, p lasm a cholinesterase. Abou t 0.04% of
u sed d u ring neuraxial blockad e at the level of the spinal p atients are hom ozygou s for this atyp ical gene and w ill
cord or p erip herally w ith nerve blocks to block transm is- have a very p rolonged neu rom u scular block follow ing
sion along m otor nerves as w ell as sensory nerves. Finally, ad ministration of su ccinylcholine. Decreased levels of
neu rom u scu lar blocking (N MB) d ru gs w ork at the level of p lasm a cholinesterase and p rolonged blockad e m ay also be
the neu rom uscular ju nction to interrupt transm ission seen in p atients w ith severe liver d isease and in p erip artu m
betw een the nerve end ing and the m uscle. N MB d ru gs are p atients.
ind icated to facilitate end otracheal intubation, and to Patients w ho receive succinylcholine may report postop-
d ecrease m u scle tone d u ring GA to im p rove su rgical w ork- erative myalgias and generalized muscle pain, w hich has
ing cond itions. been described as being similar to the pain experienced after
It m u st be em p hasized that N MB d rugs have no intrinsic intense physical exercise. The incidence of succinylcholine-
analgesic, hypnotic, or amnestic properties. These med ica- ind u ced m yalgias is varyingly rep orted from 1.5% to 89%
tions cau se com p lete ap nea and cessation of spontaneous (85). It u su ally ap p ears on the first p ostop erative d ay and
breathing. Use of N MB d rugs is ind icated only if a means of is located in the neck, shou ld ers, and u p p er abd om inal
artificial ventilation is available and feasible. m u scles. Althou gh it w ou ld seem that intense fascicu la-
There are tw o m ajor classes of m u scle relaxants: d ep o- tions are the d irect cau se of m yalgias, the exact etiology of
larizing and nond epolarizing m uscle relaxants. Regard less the d iscom fort is u nknow n and p robably com p lex (85). A
of their classification, all m uscle relaxants w ork by bind ing nu m ber of strategies have been tried in efforts to red u ce
to, and interacting w ith, prejunctional and postju nctional or abolish this ad verse effect of su ccinylcholine inclu d e
nicotinic acetylcholine recep tors at the neu rom u scu lar p retreatm ent w ith lid ocaine or a sm all d ose nond ep olar-
junction. N MB d ru gs also bind to rare extrajunctional nico- izing neu rom u scu lar blocking agent (N MBA). A m eta-
tinic recep tors, w hich are located on the m uscle fibers aw ay analysis of a large nu m ber of stu d ies revealed that the
from the neu rom u scu lar ju nction. Depolarizing m u scle m ost effective therap y w as p retreatm ent w ith 1.5 m g/ kg
relaxants m im ic acetylcholine at the postju nctional recep- of lid ocaine (86).
tors, cau sing p rolonged d epolarization. Dep olarization of Su ccinylcholine cau ses a m ean intraocu lar p ressu re
the postjunctional receptors causes m uscle contractions (IOP) increase of 4 to 7 m m H g d u e to tonic contraction of
that are qu ickly replaced by flaccid paralysis, called p hase I extraocu lar m u scles. Crying, Valsalva m aneu vers, cou gh-
block. There is only one d epolarizer in clinical u se tod ay, ing, and cricoid p ressu re all raise the IOP at least as m u ch
succinylcholine. It has a rapid onset and brief d u ration of and p erhap s m ore (87). It is a com m on belief am ong m any
action m aking it a good d ru g in situations w here tracheal anesthesiologists that su ccinylcholine is relatively con-
intu bation m u st be p erform ed rap id ly after ind u ction of traind icated for ind u ction in p atients w ith op en globe
anesthesia or w here brief relaxation is d esirable. inju ry becau se of the fear of cau sing extru sion of vitreou s
Su ccinylcholine generally cau ses an increase in the contents (87). Yet, there are no rep orts of eye d am age after
seru m p otassiu m of 0.5 to 1.0 m Eq/ L. There are certain rap id sequ ence ind u ction of anesthesia w ith thiop ental
p athologic cond itions w here the rise in p otassiu m can be and su ccinylcholine. Fu rtherm ore, a variety of stu d ies
m u ch greater. In certain cond itions, like upper m otor neu - have com p ared the change in IOP after su ccinylcholine
ron d isease (stroke, spinal cord inju ry), low er motor neu ron w ith other nond ep olarizing m u scle relaxants and fou nd
disease, muscle disease (disuse atrophy, certain m u scu lar little or no d ifference (88,89). A grou p of investigators
d ystrop hies), m u scle injury, and burns, there can be a p ro- d evelop ed a trau m a m od el in the cat eye to investigate the
liferation of extrajunctional recep tors. If succinylcholine is effects of su ccinylcholine and they fou nd that the only
ad m inistered to a patient w ith one of these cond itions, observable effect of su ccinylcholine ad m inistration w as
hyp erkalem ia m ay resu lt from efflu x of p otassiu m throu gh forw ard d isp lacem ent of the lens and iris and that no
d ep olarized extrajunctional receptors. Schow et al. retro- intraocu lar content w as lost in any case (90). Thu s, the p ro-
spectively review ed the record s from 40,000 anesthetics to scrip tion against the u se of su ccinylcholine in op en globe
evalu ate the ou tcom e follow ing the ad m inistration of su c- em ergencies ap p ears to be based m ore on theoretical con-
cinylcholine to hyperkalem ic p atients. The fou nd no cerns than evid ence. As one ed itorialist w rote, “The bene-
increased m orbid ity or m ortality d esp ite a consistent rise in fits (of su ccinylcholine) are real, the risks u np roven” (91).
the seru m p otassiu m (83). Thapa and Bru ll thorou ghly The origin and history of this d ogm a have been recently
review ed the issue of u se of su ccinylcholine in the setting review ed (92).
of renal failu re and conclu d ed that it cou ld be u sed safely Other sid e effects of su ccinylcholine inclu d e increased
as long as the p reoperative potassiu m level w as w ithin nor- ICP, increased intragastric p ressu re, and brad ycard ia (93).
m al range, there w as no neuropathy, and the d ose of su c- Su ccinylcholine is a trigger of m alignant hyp ertherm ia in
cinylcholine w as not repeated (84). su scep tible p atients.
Unlike the d epolarizers, there are a great number of non- Both atracu riu m and cisatracu riu m are m etabolized to a
d epolarizing muscle relaxants in clinical use and more are p otentially toxic m etabolite, lau d anosine. Lau d anosine
being d eveloped (94,95). N ond epolarizing muscle relaxants crosses the blood -brain barrier and m ay cau se excitem ent,
inhibit d epolarization and muscle contraction by competi- seizu re activity. In very high concentrations, lau d anosine
tively antagonizing acetylcholine at the postjunctional can cau se hyp otension and brad ycard ia. Fortu nately, accu -
receptors. Unlike succinylcholine, neurom uscular blockad e m u lation of lau d anosine and toxicity is extrem ely u nlikely
from nond epolarizers can be reversed or antagonized by in stand ard clinical p ractice, esp ecially in the case of
the ad m inistration of acetylcholinesterase inhibitors. The cisatracu riu m (97). Lau d anosine toxicity m ay be a concern
nond epolarizers vary in their onset and d uration of action, in p rolonged ad m inistration in intensive care u nits, espe-
metabolism, and sid e-effect profiles (Table 12.5). One of the cially in p ed iatric p atients and those w ith liver and renal
most d angerous consequences of use of nond epolarizing failu re. Clinically, this has not been a significant p roblem .
N MBAs is hypoventilation, hypercarbia, and hypoxem ia N MB d ru gs are u sed in critically ill patients for a vari-
follow ing inad equate or incomplete antagonism (reversal). ety of ind ications includ ing facilitation of intu bation and
A variety of d rugs and cond itions result in p rolonged block- m echanical ventilation, control of increased ICP, red uction
ad e inclu d ing aminoglycosid es (neomycin, streptomycin), of m u scle tone, and facilitation of d iagnostic and therapeu-
clind amycin, hypermagnesemia, myasthenia gravis, and tic p roced u res. Unfortu nately, u se of these med ications is
hypothermia. Combinations of d ifferent nond epolarizing associated w ith a nu mber of com p lications, m any of w hich
neuromuscular blockers can be synergistic resulting in are exactly the sam e as those seen in the op erating room ,
unexpected ly prolonged blockad e (96). su ch as skin breakd ow n, p erip heral nerve inju ry, and
Table 1 2 .5 Ch a ra ct er ist ics of com m on ly u sed n on d ep ola r izin g n eu rom u scu la r block in g a gen t s (95)
Time to 25%
Recovery from
Neuromuscular Metabolism/ Intubating Dose
Blocking Agent Class Elimination (minutes) Characteristics Notable Side Effects
Pancuronium Aminosteroid Renal 90–100 • Increased heart rate, • Cardiovascular effects may
blood pressure, precipitate myocardial
cardiac output ischemia in patients with
• Vagolytic effect on coronary artery disease
cardiac muscarinic • Residual blockadea
receptors
• Sympathetic activation
Vecuronium Aminosteroid Hepatic 40–50 • Structurally identical • Free of cardiovascular
Active metabolite to pancuronium with side effects
exception of • Residual blockade after
removal of one prolonged infusion
methyl group
Rocuronium Aminosteroid Renal, hepatic 40–45 • Rapid onset at ED95; • Anaphylactic reactions
No active metabolites alternative to reported
succinylcholine for • Recovery may be prolonged in
rapid-sequence the presence of hepatic and
induction renal impairment
Atracurium Benzylisoquinoline Spontaneous 35–40 • Histamine release • Facial flushing and
degradation at with intubating dose hypotension with rapid
physiologic pH and injection
temperature • Laudanosine metabolite may
(Hoffman elimination) cause cerebral excitation,
Hydrolysis by seizuresa
nonspecific plasma
esterases
Cisatracurium Benzylisoquinoline Spontaneous 40–50 • No significant • Free of cardiovascular
degradation at histamine release side effects
physiologic pH and
temperature (Hoffman
elimination)
a
See text for details.
corneal d esiccation. Other com plications inclu d e inad e- action, remifentanil is su ited for cases w here noxiou s stim -
qu ate sed ation and analgesia, inability to cough, throm - u lation is intense bu t brief su ch as d iagnostic laryngoscopy.
boem bolic com p lications from im m obility, and inad equ ate
ventilation in the event of d isconnection of the ventilator ■ Toxicity of anesthetics and
circu it (98). One m ajor com p lication of chronic u se of these
anesthesia (young brain)
m ed ications in critically ill p atients is the d evelop m ent of
p rolonged skeletal m u scle w eakness follow ing d iscontinu - There is increasing interest and attention in the area of
ance of N MB d ru gs. Prolonged neu rom uscu lar w eakness anesthesia-related m orbid ity and m ortality that is believed
can be d u e to either alterations in p harm akinetics or fu nc- d u e to a d etrim ental or toxic effect of anesthesia and / or the
tional d efects in the m otor unit (nerve, m uscle, or neu rostate of anesthesia. Mu ch of this w ork has focu sed on the
m u scu lar ju nction) (99). Prolonged paralysis, m u scle CN S w ith the su ggestion that certain cond itions or d iseases
w eakness, and ventilator d epend ence has been rep orted can be exacerbated by anesthetics. These cond itions inclu d e
after the ad m inistration of am inosteroid al relaxants (p an- fetal neu ronal ap op tosis, Alzheim er ’s d isease, Parkinson’s
cu roniu m , vecu roniu m ) to patients w ho are receiving d isease, H u ntington’s d isease, and p eriop erative cognitive
exogenou s steroid s or w ho have liver or renal failu re d ysfu nction. A nu m ber of excellent review articles d iscu ss
(100,101). This cond ition has also been reported after the this m aterial in d ep th (108–111).
ad m inistration of d ru gs of the benzylisoquinoliniu m class The d evelop ing nervou s system is highly su scep tible to
(atracu riu m , cisatracurium ) (102,103). Resou rces are avail- neu rotoxic insu lts. Du ring (fetal) d evelop m ent of the CN S,
able that m ake specific recom m end ations regard ing the the brain u nd ergoes rapid grow th and synaptogenesis,
ind ications, choice of d rugs, d osage, and m onitoring w hich is accom panied by program m ed neu ronal cell d eath
(98,99,104). or “su icid e,” also know n as ap op tosis. In the brain, apopto-
sis is an energy-d riven p rocess that is norm ally triggered
Analgesics by lack of synap tic feed back d u e to failure to form synap tic
The op ioid agonists are used as p reoperative sed atives, as connections. Ap op tosis can be ind u ced by either d eath of
ad ju ncts to the PIAs in balanced anesthesia, as p ostop era- an innervating cell, lead ing to a trop hic d ep rivation inju ry,
tive analgesics, and as ad ju ncts in neu raxial blockad e. Mor- or by a toxic stim u lu s that is insu fficient to cau se necrosis
p hine is the p rototypical op ioid agonist w ith analgesic (by itself).
p rop erties (30). It also cau ses respiratory d ep ression, It is w ell accep ted that ethanol d am ages the d evelop ing
ap nea, nau sea, and vom iting through CN S m echanism s. hu m an brain and fetal exp osu re to alcohol has the p otential
Morp hine ad m inistration is accom panied by histam ine to cau se a sp ectru m of neu robehavioral d istu rbances rang-
release, w hich may cau se significant vasod ilation and ing from relatively m ild hyp eractivity, attention d eficits,
hypotension, especially in hypovolemic patients. Large and learning d isabilities (LD) to severe m ental retard ation.
d oses m ay cau se sinu s brad ycard ia. Morphine cau ses Bu t it w as the u niqu e craniofacial abnorm alities of fetal
constipation, spasm of the sphincter of Od d i, and d elayed alcohol synd rom e that led investigators to u ncover the fu ll
gastric emptying. spectru m of m anifestations that inclu d e neu ronal d am age,
Mep erid ine is stru ctu rally sim ilar to atrop ine and can p hysical d eform ities, m ental im p airm ent, and behavioral
cau se tachycard ia bu t is otherw ise w ell tolerated in healthy p roblem s that occu r w hen the d eveloping em bryo is
p atients. Very large d oses can cause clinically significant exp osed to ethanol. Stu d ies p erform ed in anim als to elu ci-
hyp otension throu gh d ecreased p erip heral vascu lar resist- d ate the m echanism of ethanol-ind u ced CN S d am age su g-
ance and d ecreased card iac outpu t. Meperid ine also cau ses gest that neu rotoxic effects are d u e to trop hic d ep rivation
histam ine release, like morphine (105). Unique to m ep eri- lead ing to ap op totic neu rod egeneration. Because ethanol,
d ine u se are the sid e effects of serotonergic crisis and like m any anesthetics, interru p ts synap tic transm ission by
norm ep erid ine toxicity. N orm eperid ine is a m etabolite of a com bination of activation of GABA and antagonism of
m ep erid ine that can cau se CN S excitation and convu lsions. N MDA recep tors, stu d ies w ere cond u cted to investigate
N orm ep erid ine has a long elimination half-life and can the p ossibility that anesthetics m ay trigger sim ilar neu-
accu m u late in renal failu re. Postoperative neu rotoxicity rod egenerative processes.
has been observed in p atients receiving large d oses of Early clinical stu d ies su ggested that child ren exp osed to
m ep erid ine via p atient-controlled anesthesia (106). anesthesia and su rgery d evelop ed p ersonality changes
Fentanyl, su fentanil, alfentanil, and rem ifentanil are inclu d ing tem p er tantru m s, p hobias, and bed -w etting.
p otent synthetic op ioid s that cau se respiratory d epression, Early anim al stu d ies that w ere d esigned to test the effect of
ap nea, and brad ycard ia (30). Large d oses of the synthetic anesthesia on fetu ses fou nd that the offsp ring of pregnant
opioid s can p rod uce chest w all rigid ity, w hich m ay be p re- m ice exp osed to halothane p erform ed significantly m ore
vented by p retreatm ent w ith a nond epolarizing neurom u s- slow ly than control mice. In 2003, a land m ark anim al stud y
cu lar blocker. Rem ifentanil is u nique becau se of its rap id by Jevtovic-Tod orovic et al. w as p u blished that suggested
elim ination by p lasm a and tissu e esterases allow ing this that exposu re of the d eveloping rat brain to “com m on
agent to be rap id ly titrated via continu ous IV infu sion anesthetic agents” cau sed w id esp read neu rod egeneration
(107). Becau se of its rapid onset and very brief d u ration of and su bsequ ent, p ersistent learning d eficits (112). These
investigators ad m inistered a com bination of d ru gs com - In su mm ary, d ata from a nu m ber of anim al stu d ies (pri-
monly u sed in p ed iatric anesthesia (m id azolam , nitrou s m arily rod ents) ind icate that anesthetic agents are toxic to
oxid e, and isoflu rane) to 7-d ay-old infant rats in d oses the you ng brain and that this inju ry resu lts in a long-term
su fficient to m aintain a su rgical p lane of anesthesia for im p airm ent of cognitive fu nction (117). While increased
6 hours, and observed w id espread apoptotic neu rod egen- ap op tosis and neu rod egeneration have been observed in
eration in the d eveloping brain as d etected by caspase-3 m u ltip le areas of the brain of you ng anim als exp osed to
activation, silver staining, and / or electron m icroscop y. In GABA agonists and N MDA antagonists, the hip p ocam p us
ad d ition, a battery of behavioral tests revealed im p aired ap p ears esp ecially vu lnerable. This neu rotoxicity has been
mem ory and learning. Several su bsequent stu d ies by the d em onstrated not only for the inhaled agents isoflu rane
sam e grou p and others have au gm ented these find ings an d nitrou s oxid e bu t also for IV sed ative-hyp notics
(109). For exam p le, Fred riksson et al. injected 10-d ay-old su ch as ketam ine, m id azolam , d iazep am , p entobarbital,
mice w ith ketam ine, prop ofol, thiopental, prop ofol w ith thiop ental, and p rop ofol. N onanesthetic su bstances have
thiopental, ketam ine w ith p ropofol, high-d ose propofol, or d em onstrated sim ilar neu rotoxicity. Stu d ies have su g-
saline (control). Flu oro-Jad e staining w as used to d etect gested that apoptotic neu rogeneration occu rs after both
neu rod egeneration 24 hou rs after treatm ent in a subset of p rolonged exp osu re and brief exp osu re, fu lly anesthetic
mice. Mice aged 55–70 d ays w ere subjected to a battery of d oses, and su banesthetic d oses. Fu rtherm ore, exp erim ental
behavioral tests. Their results d em onstrated that both a m od els have exclu d ed hyp oxia/ ischem ia and hyp o-
-am inobu tyric acid typ e A agonist (thiop ental or p rop o- glycem ia as p ossible alternative contribu ting factors. It has
fol) and an N MDA antagonist (ketam ine) ad m inistered not been established that hum ans are susceptible to this
d u ring a critical stage of brain d evelop m ent potentiated neu rotoxicity. N eed less to say, the early resu lts of this
neonatal brain cell d eath and resulted in functional d eficits evolving line of p reclinical evid ence have the potential to
in ad u lthood (113). Discoveries that agents such as m ela- significantly im p act the cond u ct of anesthesia, esp ecially in
tonin, erythrop oietin, and xenon red uce neurod egenera- obstetrics and p ed iatrics. The controversial natu re of the
tive d am age in d evelop ing brains exp osed to anesthesia, w ork has sp arked a vigorou s d ebate betw een the investiga-
offer p otential strategies for neu roprotection (114). tors w ho have generated m u ch of the (anim al) evid ence
Clinical stu d ies aim ed at ad d ressing the potential for and those w ho argu e that available d ata in hu m ans suggest
long-term neurobehavioral consequ ences of anesthetic that anesthesia and anesthetic d ru gs p ose very little risk to
exposu re su ffer from a nu m ber of lim itations includ ing the d evelop ing hu m an brain (110).
absence of d irect exam ination on neu rod evelopm ental ou t- While som e have gone so far as to ad vocate, “w e shou ld
com e, insu fficient tim e for follow -u p assessm ent of long- m inim ize or avoid late third -trim ester anesthesia, d elay
term ou tcom e, and lack of w ell-d efined end points in elective su rgery in p reterm and p ostnatal infants, avoid
outcom e. Tw o recent stud ies u sed retrosp ective cohorts of nitrous oxid e and ketamine becau se they seem to the m ost
infants to exam ine the effects of anesthetic exposu re in toxic anesthetics, and lim it su rgical p roced u re tim es w hen-
infants after su rgery and anesthesia (115,116). Kalkm an ever p ossible,” all agree that it is u naccep table not to pro-
et al. sent qu estionnaires to the parents of 314 child ren w ho vid e anesthesia d u ring su rgical and m inor p roced ures. The
w ere op erated for p ed iatric u rological p roced u res betw een d eleteriou s effects of inad equ ate analgesia and anesthesia
the ages of 0 and 6 years. They chose u rologic su rgery in neonates and child ren are w ell accepted .
becau se in this area m any solitary urogenital anom alies
exist u naccom p anied by general illness. They fou nd that ■ Toxicity of anesthetics and anesthesia
child ren u nd ergoing su rgery and anesthesia at age less
(older brain)
than 24 m onths show ed m ore behavioral d istu rbances than
child ren in w hom su rgery w as performed after age 2 years, The old er brain is also m ore vu lnerable to p otential neu ro-
bu t the resu lts w ere not statistically significant and the stu d y toxic effects of su rgery, anesthesia, and anesthetics. The
w as u nd erp ow ered . Wild er et al. u sed the cohort of all chil- old er brain has less cognitive reserve and is less resilient to
d ren born to m others resid ing in five tow nships of Olm sted stress and insu lts. In general, eld erly p atients require less
Cou nty, Minnesota over a p eriod of 5 years. They exam ined anesthesia as ind icated by a low er m inim u m alveolar con-
the ed u cational and m ed ical record s to id entify child ren centration and m inim um intra-arterial concentration.
w ith LD. Of the 5,357 child ren in this cohort, 593 received Unlike the p ed iatric p op u lation, w here there are ju st
GA before age 4 years. Com p ared w ith those not receiving now hints of longer-lasting cognitive d eficits follow ing su r-
anesthesia, a single exp osu re to anesthesia w as not associ- gery and anesthesia, the occu rrence of p ostop erative cogni-
ated w ith an increased risk of LD, bu t child ren receiving tive d ysfu nction (POCD) is w ell d escribed in the ad u lt
tw o or m ore anesthetics w ere at increased risk for LD. p op u lation. Dep end ing on the stu d y and m ethod of d etec-
While both of these stu d ies have lim itations that are d is- tion, POCD m ay be d etectable in betw een 12% and 25% of
cu ssed in an accom panying ed itorial, the find ings are eld erly p atients in the first few w eeks and m onths follow -
provocative and su ggest the need for further research. ing su rgery (118). Risk factors for su stained POCD in non-
Im portantly, they cannot be consid ered to p rovid e evi- card iac su rgery inclu d e age, d u ration of anesthesia, less
d ence of anesthetic neurotoxicity in child ren (108). ed u cation, POCD at hosp ital d ischarge, and history of
stroke w ithou t resid ual d am age. Som e investigators have exp eriences as the p eop le in the w ell-p u blicized cases in
fou nd a su bstantial relation betw een POCD and d eath new sp ap ers, television talk show s, and on the Internet.
w ithin 1 year of su rgery (119). Aw areness d u ring GA can be a horrifying exp erience, and
Postop erative cognitive d ysfunction is even m ore fre- it can leave p atients w ith a range of p roblem s from tem po-
qu ent after card iac su rgery. N ew m an et al. found POCD in rary em otional d istress to long-lasting p ost-trau m atic
53% of coronary artery bypass graft (CABG) patients at d is- stress d isord er (127). This com p lication cau ses consid er-
charge and 36% of p atients 6 w eeks later (120). Risk factors able d istress for p ractitioners as w ell as for p atients.
for POCD in card iac su rgery are sim ilar to those for non- In closed claims analysis, aw areness accou nted for 1.9%
card iac su rgery. While m any stud ies have been p erform ed of 4,183 claim s over a p eriod of over 20 years bu t the great-
in CABG su rgery, card iac surgery inclu d es a variety of est p rop ortion of claim s occu rred d u ring the 1990s (128).
op erations p erform ed on the heart and great vessels u sing Most claim s involved w om en (77%), p atients younger than
card iopulmonary bypass. Card iopulmonary bypass, preva- age 60 (89%), ASA class I or II (68%), and elective su rgery
lence of atherosclerotic d isease, and the technical natu re of (87%). The au thors u sed the term , “aw ake p aralysis,” to
heart su rgery p lace p atients at increased risk of cerebral d escribe inad vertent p aralysis of an aw ake p atient and
em bolic events, cerebral ischem ia d uring reperfu sion, and m ost of these cases w ere d u e to m ed ication infu sion errors
cerebral inju ry from overzealou s rew arm ing at the end of or syringe sw ap s. Most claim s w ere for “recall d u ring anes-
the proced u re. thesia,” w hich im p lied recall of events w hile receiving GA.
The p otential contribu tion of anesthetic neu rotoxicity to These claim s w ere associated w ith the absence of a volatile
POCD is u ncertain. Preclinical in vitro and in vivo stu d ies anesthetic (nitrou s-narcotic-relaxant techniqu e), fem ale
w ith anim als provid e evid ence that inhaled anesthetics gend er, obstetrics/ gynecology op eration, intra-op erative
interact w ith recognized p athw ays for neu rod egeneration op ioid , and the u se of N MBAs. N MBAs, as a com ponent of
and p rod u ce effects consistent w ith intracellular stress. In “balanced anesthesia,” allow low er concentrations of
som e cases, su ch as ischemic precond itioning (in the heart volatile anesthetics to be u sed than w ou ld otherw ise be
and brain) these processes m ay be protective. Som e anim al necessary to p revent m ovem ent. Patient m ovem ent is a
stu d ies suggest that inhaled anesthetic exposure increases sign of inad equ ate anesthesia and ablation of m ovem ent,
p athology norm ally associated w ith Alzheim er ’s d isease, along w ith u sing low er concentrations of volatiles, m ake
specifically casp ase activation, increases in -am yloid p ep - aw areness a risk. A large, retrosp ective analysis of a d ata-
tid e and -acting cleavage enzym e, and phosp horylated base of anesthetic incid ent rep orts cou ld not establish a
tau in brain tissue. Associated w ith this are behavioral cau se of aw areness in 16% of cases (129). Forty-fou r percent
stu d ies in ad u lt w ild -type rats and m ice that d emonstrate of cases w ere related to low insp ired volatile anesthetic
that isoflu rane exposu re alone prod u ces d ecrem ents in concentrations (or inad equ ate hyp nosis) d u e to p roblem s
learning and m em ory that p ersist for w eeks or m onths. w ith vap orizers, breathing circu its, or agent m onitors, pro-
longed attem p ts at intu bation, or red u ction in inspired
volatile concentrations because of hem od ynam ic instability.
■ Intra-operative awareness The rem aining forty p ercent w ere cau sed by d ru g errors
In a large survey of public attitud es tow ard preop erative d u e to inattention, d istraction, haste, or fatigu e. In a m ore
assessm ent and risk, m ore respond ents w ere concerned recent review of aw areness, Ghoneim com pared 271
abou t m em ory loss and interop erative aw areness than rep orted cases of intra-op erative aw areness w ith 19,504
w ere concerned abou t d eath (121). Unfortu nately, the inci- control cases com p iled from other stu d ies (130). These
d ence of intra-op erative aw areness is p robably m u ch investigators found that aw are p atients w ere m ore likely to
higher than the rate that is reported in the literatu re (0.2% be fem ale, you nger, and to have card iac or obstetric opera-
to 1.0%) (122,123). Recollection, or recall, of intra-op erative tions. Aw areness w as associated w ith light anesthesia and
events u nd erestim ates aw areness becau se not all p atients few er anesthetic m ed ications ad m inistered (excep t neu ro-
w ho w ere aw are of events d u ring an operation can rem em - m u scu lar blockers), inclu d ing p reop erative sed ation.
ber the fact afterw ard (124). When a forearm is isolated About one-qu arter of the aw are p atients received no
from exp osu re to m u scle relaxants d u ring anesthesia, arm volatile anesthetic or p rop ofol d u ring m aintenance of anes-
m ovem ents can be u sed to assess p ercep tion and resp onse thesia, bu t the u se of nitrou s oxid e d id not m ake a d iffer-
to com m and s. Many stud ies have u sed this techniqu e to ence in the incid ence of aw areness. Table 12.6 lists m ethod s
establish that conscious perception can occu r, w ith or w ith- to red u ce the incid ence of aw areness and step s to take in
ou t exp licit m em ory formation, in an app arently anes- response to a case of aw areness.
thetized p atient (124,125). The incid ence of aw areness
d ep end s on the type of anesthesia, strength of stim u lu s,
and the tim ing and m ethod u sed to elicit recall. For exam -
■ Immunosuppression
p le, card iac su rgery is associated w ith an incid ence of The effect of anesthetics on the im m u ne system has been
aw areness u p to 23% (126). An incid ence of 0.2% w ou ld recently review ed (131). The im m u nological effects of su r-
suggest at least 30,000 cases of aw areness p er year in the gery and anesthetics m ay have an im p ortant affect on the
Un ited States; clearly, m an y p atients share the sam e long-term ou tcom es of p atients after su rgery, especially in
Table 1 2 . 6 In t ra -op era t ive awa r en ess

Steps to Take Following a Complaint of Awareness During
Measures for Preventing Intra-operative Awareness (129,231) General Anesthesia (124)
• Consider amnestic agents for premedication (midazolam, scopolamine) • Visit the patient as soon as possible, along with a witness
• Maintain and service anesthesia equipment regularly. Check the anesthe- • Document the patient’s history and exact memory of events; keep a
sia machine before each use, ensuring a correctly mounted vaporizer copy of the account
• Use an end-tidal agent monitor, with the low alarm set for a sufficient • Attempt to confirm the validity of the account, if necessary
volatile concentration to prevent awareness • Provide the patient with a full explanation of the events
• Use an adequate dose of induction agents. Provide additional doses of • Offer the patient follow-up, including psychological support, and
hypnotic for repeated intubation attempts document that this has been offered
• Supplement nitrous/opiate technique with potent volatile agent • Reassure the patient that they can have further general anesthet-
• Supplement potent volatile agents with nitrous oxide and/or ensure ics with minimal risk of further episodes of awareness
adequate concentrations of volatile anesthetics • If the cause of the awareness episode is not known, try to deter-
• Be aware of the potential for awareness in hypovolemic patients with low mine it
concentrations of hypnotic; introduce these as soon as is practical • Notify risk management and hospital administration
• Use muscle relaxants only when indicated. Routinely use a peripheral • Notify surgeon and primary care physician
nerve stimulator, and ensure sufficient anesthesia until muscle strength
returns
• When using total intravenous anesthesia, maintain a patent, secure intra-
venous line and periodically check the volume in the syringe to ensure the
barrel is advancing
• Clearly label all drug syringes immediately as they are drawn up; check this
label carefully, and do not rely on recognition of syringe size to confirm its
contents; consider other methods of ensuring correct drug given.
• Mask auditory input
• Consider use of depth of anesthesia monitor, if not routinely, then for
selected cases
those p atients w ith cancer, infection, or altered im m u no- op ioid s, w hich m ay have im p lications for the choice of
com petency at baseline. The m ain cau ses of imp aired or anesthetics in im m u nocom p rom ised p atients.
altered im m u ne resp onses in surgical patients are believed
to be related to the neuroend ocrine stress exerted throu gh
activation of the au tonom ic nervou s system and the ■ NEURAXIAL, REGIONAL, NERVE BLOCKS
hyp othalam ic-p itu itary-ad renal axis. In ad d ition, blood ■ Local anesthetic toxicity
transfu sions, p ersistent hyperglycem ia, intra-op erative
hypothermia, and severe p ostoperative p ain are associated Local anesthetics are frequ ently u sed in a w id e variety of
w ith p eriop erative imm u nosu ppression. While “im m u no- techniqu es by both anesthesiologists and su rgeons. The
supp ression” or “anti-inflamm atory action” m ay have efficacy of local anesthetics in p rovid ing anesthesia for
d eleteriou s effects in some d isease processes, it m ay be local injection, regional nerve blockad e, central neuraxial
d esirable or beneficial in others. blockad e, and p ostop erative analgesia is clear. Unfortu -
Recently, nu m erou s stud ies have show n that anesthet- nately, local anesthetics are also associated w ith a w id e
ics and analgesic agents com m only u sed in su rgery and in variety of ad verse events or com p lications, som e of w hich
intensive care m ay d irectly affect the fu nctions of im m u ne- can be seriou s. These ad verse reactions inclu d e allergic
com petent cells bu t, in com parison to su rgical stress, anes- reactions, system ic toxicity, tissu e-related neu rotoxicity,
thetics probably have a m inor effect on the im m u ne system and m yotoxicity.
in patients u nd ergoing su rgery. The volatile anesthetics
have an inhibitory effect on neu trop hil fu nction p rim arily Local Anesthetic Systemic Toxicity
throu gh suppression of p rod uction of reactive oxygen It has long been recognized that ad m inistration of local
species. Variou s stu d ies have show n inhibitory effects of anesthetics can be follow ed by seizu res, resp iratory failu re
volatile anesthetics on lym phocyte proliferation and sup- and card iovascu lar collap se. Local anesthetic system ic tox-
p ressive effects of these agents on cytokine release in icity (LAST) p rim arily involves the neu rological system
p erip heral blood m ononuclear cells. One m echanism m ay and the card iovascu lar system. While m ild neurologic
involve ind u ction of lym p hocyte ap op tosis by volatile sym ptom s may follow system ic absorption of local anes-
anesthetics. Interestingly, the accum u lated evid ence su g- thetic from a correctly sited and appropriately d osed
gests that im m u nocom p etent cells seem to be m ore sensi- regional anesthetic p roced u re, severe CN S and / or card io-
tive to volatile anesthetics than to propofol or synthetic vascu lar toxicity is usu ally the resu lt of unintentional
FIGURE 12.3. Systemic toxicity symptoms of local anesthetics.

The systemic symptoms associated with toxicity due to local anes-
thetics are represented on a scale corresponding to the approximate
plasma lidocaine concentrations that produce the symptoms. In gen-
Ca rdiova s cula r colla ps e eral, cardiovascular toxicity occurs at levels that are three times the
Ve ntricula r a rrhythmia s levels that produce CNS toxicity. (Modified from Brown DL. Local
S inus bra dyca rdia anesthetic toxicity. In: Finucane BT, ed. Complications of regional
90 anesthesia. Philadelphia, PA: Churchill Livingstone; 1999.)
Myoca rdia l conduction
a bnorma litie s
P rofound hypote ns ion
85
Pe riphe ra l va s odila tion
Myoca rdia l de pre s s ion
Mode ra te hype rte ns ion
80
Lidoca ine
pla s ma
conc 30
(g .mL-1 )
25
CNS de pre s s ion
20
Re s pira tory a rre s t
Coma
15
Convuls ions
Uncons cious ne s s
10 Mus cula r twitching
Vis ua l dis turba nce
Light-he a de dne s s
5 Numbne s s of tongue
intravascu lar injection or the ad m inistration of excessive

amou nts. The incid ence of system ic local anesthetic toxicity
has d ecreased in recent years, and is estim ated to be
betw een 7.5 and 20 per 10,000 cases (132) (Fig. 12.3).
H igh local anesthetic levels in the blood of the CN S ini- Inte rple ura l
tially resu lt in excitation, w hich is d u e to blockad e of neu ral
inhibitory p athw ays in the am ygd ala (133). As blood levels Inte rcos ta l
rise, both inhibitory and excitatory pathw ays are inhibited , Ca uda l
and excitation is follow ed by CN S d epression. Early sym p -
tom s inclu d e light-head ed ness, d izziness, visu al changes, Epidura l
and tinnitu s. Shivering, m uscle tw itching, and trem ors
Bra chia l plexus
may p reced e generalized tonic-clonic seizures. Seizu res
may d evelop im m ed iately if high blood levels are achieved Fe mora l-s cia tic
very rap id ly, as in an intravascular injection into a blood
vessel su p p lying the brain. H ypoventilation, hyp ercarbia, S ubcuta ne ous
and acid osis low er the seizu re threshold , presu m ably Intra -a rticula r
throu gh increased cerebral blood flow and increased
up take of local anesthetic in the brain (Fig. 12.4). S pina l
Card iovascular side effects are generally seen at higher
blood levels than those that cause CNS toxicity (134). Car-
diovascular toxicity is due to effects on both the vasculature
and the heart. In the heart, both electrical and mechanical
activity is affected. Local anesthetics inhibit sodium chan- FIGURE 12.4. Ranking of peak blood levels of local anesthetics following a
variety of regional blocks. (Reprinted with permission from Brown DL. Local
nels, prolonging conduction time and depressing sponta- anesthetic toxicity. In: Finucane BT, ed. Complications of regional anesthesia.
neous pacemaker activity. There have been case reports of Philadelphia, PA: Churchill Livingstone; 1999.)
cardiac arrest with electrical standstill as a part of bupiva- Table 1 2 .7 Toxicit y of loca l a n est h et ics
caine toxicity. Many of these cases w ere reported in young
healthy parturients receiving bupivacaine epidural anesthe- Toxic Plasma
Equieffective Concentration
sia and / or analgesia for labor and w ere associated w ith d if-
Drug Maximum Dose Concentration ( g/mL)
ficult, prolonged , and occasionally futile resuscitation (132).
Development and recovery from block d iffers betw een bupi- Lidocaine 4 mg/kg 1% (10 mg/mL) 5
vacaine and lidocaine, helping to explain the greater cardiac 300–500 mg
toxicity w ith bupivacaine (135). Lidocaine blocks channels in Bupivacaine 2 mg/kg 0.25% (2.5 mg/mL) 1.5
a “fast-in, fast-out” fashion, allow ing recovery of the sod ium 175–200 mg
channel for a portion of the cardiac cycle. Bupivacaine, on
Note: A 1% solution contains 10 milligrams per milliliter.
the other hand , blocks sodium channels in a “slow -in, slow -
out” manner at low concentrations, and a “fast-in, slow-out”
manner at high concentrations. Thus, bupivacaine blocks the
sod ium channels throughout the cardiac cycle leaving no
opportunity for sod ium channel recovery. (140). For exam p le, even a sm all am ou nt of d ru g injected
Clinically, tachycard ia and hypertension accom p any into an artery su p p lying the brain w ill cau se seizu res. The
CN S toxicity. As blood levels of local anesthetics continue to site of injection and the p resence of vasoconstrictors affect
rise, there is myocard ial d epression, hyp ertension, and toxicity, also. In general, ep inep hrine d ecreases the peak
d ecreased card iac outp ut. At even higher blood levels, p lasm a concentration of local anesthetic after it is injected
peripheral vasod ilation, profound hypotension, cond u ction bu t the m agnitu d e of this affect d ep end s on both the local
abnorm alities, sinus brad ycard ia and ventricular arrhyth- anesthetic and the site of injection (141). Finally, there are
mias lead to card iovascular collapse. H ypoxemia and aci- variations in the resp onse of ind ivid u al p atients to d ifferent
d osis often accom pany seizu res and card iovascular collapse d oses of local anesthetics. Read ers are referred to an excel-
and can potentiate local anesthetic-ind uced myocard ial lent review on this top ic (139).
d epression. The cu rrent Am erican Society of Regional Anesthesia
Card iovascular toxicity is influenced by a num ber of (ASRA) p ractice ad visory em p hasizes the im p ortance of
factors. The ratio betw een d oses that cause card iovascu lar p revention in red u cing the frequ ency and severity of LAST
toxicity and central nervous toxicity varies w ith each local (Table 12.8). The p ractice ad visory lists a nu m ber of m eth-
anesthetic (136). For exam p le, the card iovascu lar toxicity od s to red u ce the likelihood of LAST, recognizing that there
to CN S toxicity ratio is low er w ith bup ivacaine than for is not a single m easu re that can p revent LAST in clinical
lid ocaine. Interestingly, the m echanism s of lethal toxicity p ractice. The low est effective d ose of local anesthetic
ap pear to d iffer am ong local anesthetics in both consciou s shou ld be u sed , and the injection of relatively large vol-
and anesthetized su bjects. For exam ple, IV bup ivacaine is u m es of local anesthetic shou ld be d one in increm ents
m ore likely to p rod u ce d eath by the su d d en onset of lethal red ucing the potential toxic d ose if it is inad vertently
d ysrhythm ias, w hile IV lid ocaine is more likely to prod u ce injected intravascu larly. Avoid ing, or rap id ly d etecting, an
d eath throu gh p rogressive m yocard ial d ep ression and con- u nintentional intravascu lar injection is central to prevent-
tractile failu re. In anim als, IV ropivacaine and levobu p iva- ing seriou s toxicity. Intravascu lar injection may be d etected
caine have p rod u ced fatalities by either m echanism , and it by increm ental asp iration after p ositioning the need le or
is not yet clear w hat m akes one ou tcom e m ore likely than catheter and by ad d ing an intravascu lar m arker to the local
the other in ind ivid u al cases (137). anesthetic. An intravascu lar “test d osing” rem ains the m ost
Both the CN S effects and card iovascu lar effects are p ri- reliable m arker of intravascu lar injection. Ten to fifteen
m arily associated w ith high levels of local anesthetic in the m icrogram s p er m illiliter of ep inep hrine ad d ed to the local
blood . Besid es the sp ecific local anesthetic and total local anesthetic has a p ositive p red ictive valu e and a sensitivity
anesthetic d ose, a variety of other factors influ ence the like- of 80% in d etecting intravascu lar injection in ad u lts. Epi-
lihood and severity of LAST, inclu d ing ind ivid u al p atient nephrine test d oses are u nreliable in patients w ho are eld -
risk factors, concu rrent m ed ications, location and tech- erly, taking -blockers, sed ated , or anesthetized (132).
niqu e of the block, tim eliness of d etection, and ad equ acy of Ultrasound guid ance of injection of local anesthetics
treatm ent. LAST can occur second ary to tissue absorp tion and p lacem ent of infu sion catheters m ay red u ce the fre-
of a large am ou nt of local anesthetic. Acute toxicity can also qu ency of com p lications from regional anesthesia inclu d -
be cau sed by accid ental intravascular injection of a sub- ing intravascular injection bu t there are no trials that
m axim al d ose, occasionally intra-arterial bu t m ore com - confirm or refu te and actu al red u ction in the incid ence of
m only IV. Unfortu nately, it is very d ifficult to establish a LAST (142).
m axim al d ose for each local anesthetic even thou gh su ch Treatm ent p riorities for LAST are ou tlined in the ASRA
inform ation is available in textbooks (Table 12.7) (138,139). p ractice ad visory and inclu d e airw ay m anagem ent, circu -
Furtherm ore, m any episod es of LAST are d ue to u ninten- latory su p p ort, and red u cing the system ic effects of local
tional intravascular injection of a su bm axim al d ose rather an esth etics. Clearly, the su ccess of an y resu scitation
than u ptake of excessive d oses from regional blockad e effort d ep end s on ad equ ate p rep ared ness that inclu d es the
Table 1 2 . 8 Loca l An est h et ic Syst em ic Toxicit y

For Patients Experiencing Signs or Symptoms of Local Anesthetic Systemic Toxicity (LAST)
• Get Help
• Initial Focus
• Airway management: ventilate with 100% oxygen
• Seizure suppression: benzodiazepines are preferred
• Basic and Advanced Cardiac Life Support (BLS/ACLS) may require prolonged effort
• Infuse 20% Lipid Emulsion (values in parenthesis are for a 70 kg patient)
• Bolus 1.5 mL/kg (lean body mass) intravenously over 1 min (∼100 mL)
• Continuous infusion at 0.25 mL/kg/min (∼18 mL/min)
• Repeat bolus once or twice for persistent cardiovascular collapse
• Double the infusion rate to 0.5 mL/kg per minute if blood pressure remains low
• Continue infusion for at least 10 min after attaining circulatory stability
• Recommended upper limit: approximately 10 mL/kg lipid emulsion over the first 30 min
• Avoid vasopressin, calcium channel blockers, -blockers, or local anesthetic
• Alert the nearest facility having cardiopulmonary bypass capability
• Avoid propofol in patients having signs of cardiovascular instability
• Post LAST events at www.lipidrescue.org and report use of lipid to www.lipidregistry.org
Adapted from the ASRA Practice Advisory on Treatment of Local Anesthetic Systemic Toxicity. For more complete recommendations,
see Table 4 of reference (142).
availability of p roperly trained staff and equ ip m ent to p ro- w ere m ore resistant to the card iac effects of bu p ivacaine
vid e basic and ad vanced life su pport. System ic toxicity than nontreated rats. Su bsequ ent stu d ies w ere perform ed
mu st be rapid ly d iagnosed recognizing that CN S and car- to sp ecifically investigate the effect of lip id em u lsions on
d iac toxicity m ay present sim u ltaneou sly or card iac toxic- resu scitation from bu p ivacaine-ind u ced card iac toxicity.
ity m ay occur in the absence of prod rom al signs and Card iac arrest w as ind u ced in anim als w ith a toxic d ose of
sym p tom s of CN S toxicity. Isolated CN S toxic resp onses bu p ivacaine. Anim als treated w ith a lip id em u lsion d u ring
are best treated w ith rapid ad m inistration of sup p lem ental resu scitation w ere m ore likely to recover card iac fu nction.
oxygen, benzod iazepines or barbitu rates, and su p p ortive Sm all anim al stu d ies w ere su p p orted by su bsequ ent w ork
measu res. Intu bation and ventilation is rarely necessary for in d ogs. A large d ose of bu p ivacaine (10 m L/ kg) w as
isolated CN S toxicity. injected as a bolu s into d ogs w hile u nd er GA. Card iac
Card iac toxicity u su ally requires aggressive and p ro- arrest w as treated w ith op en chest m assage alone or in
longed resuscitation m easu res and pharm acological su p- com bination w ith an infu sion of 20% lip id emu lsion, given
port in accord ance w ith Ad vanced Card iac Life Su p p ort as a bolu s follow ed by continu ou s infu sion. All d ogs d evel-
(ACLS) p rotocols. The p ractice ad visory em phasizes the op ed card iac toxicity as m anifested by severe hyp otension
im portance of im m ed iate restoration of oxygenation and and brad ycard ia. All lip id treated anim als w ere su ccess-
ventilation in facilitating su ccessfu l resu scitation and halt- fu lly resu scitated to norm al hem od ynam ics w hile all con-
ing the p rogression to card iovascu lar collapse. Local anes- trol d ogs d ied (143).
thetic ind u ced card iac arrest requ ires rap id restoration of These encouraging results in animal stud ies have been
coronary p erfusion pressure to imp rove m yocard ial con- supported by a number of case reports of successful resusci-
tractility and m aintain card iac output. The practice ad vi- tation from refractory card iac arrest after the ad ministration
sory also recognizes the efficacy of lip id em u lsion therap y of lipid em ulsion. In one such case, a mid d le-aged man w ith
in facilitating resuscitation, m ost probably by acting as a heart d isease su ffered card iac arrest shortly after p lacem ent
“lip id sink” that low ers the concentration of lip id -solu ble of a brachial plexus block using bupivacaine and mepiva-
local anesthetic w ithin card iac tissue thereby im proving caine. The patient rem ained in asystole w ith intermittent
contractility, cond u ction, and coronary perfu sion (142). ventricular tachycard ia and ventricular fibrillation d espite
20 minutes of stand ard ACLS, w hich includ ed several cou n-
Lipid Emulsion Therapy for LAST tershocks and multiple d oses of epinep hrine, atropine,
In ad d ition, the ad visory d escribes the use of intralip id as amiod arone, and vasop ressin. Within minutes of an infu-
an antid ote to LAST. Recently, num erou s case rep orts and sion of 100 mL of 20% Intralipid , the patient’s heart started
many anim al stud ies have sup ported the use of IV lipid beating, and this w as follow ed almost immed iately by
em ulsion in card iac toxicity that is refractory to conven- return of norm al sinu s rhythm and blood pressu re. The
tional therap y. While stu d ying the m etabolic effects of patient recovered w ithout neu rological d eficit.
bu p ivacaine, Weinberg et al. m ad e the serend ipitou s obser- Su bsequ ent stu d ies in anim al m od els have show n
vation that rats p retreated w ith a lip id soy bean em u lsion conflicting resu lts. For exam p le, ad m inistration of lip id
em u lsion actu ally d im in ished th e retu rn of sp ontan eou s Experimentally, all local anesthetics, inclu d ing cocaine,
circu lation in rats su bjected to n ond ru g-ind u ced , h yp oxic are p otentially myotoxic. Experimental myotoxic effects of
card iac arrest. Mayr et al. com p ared the com bination of local anesthetics are characterized by hypercontracted
vasop ressin an d ep inep hrin e versu s lip id em u lsion in a m yofibrils, follow ed by lytic d egeneration of striated mu s-
p orcine m od el of asp hyxial, card iac arrest follow ing cle sarcoplasmic reticulum, myocyte ed ema, and finally
bu p ivacain e in fu sion. In th eir m od el, p igs received an necrosis (145). These effects are intense and reprod ucible. Of
infu sion of 5 m g/ kg of a 0.5% bu p ivacain e solu tion IV the local anesthetics stu d ied , bu pivacaine and levobup iva-
and ventilation w as interru p ted for ap p roxim ately 2 m in- caine p rod u ce the most severe muscle inju ry (146,147).
u tes u ntil asystole d evelop ed . After 2 m inu tes of car- Many anesthesiologists and pain p hysicians recognize that
d iop u lm onary resu scitation (CPR), 10 anim als received , intramuscular injections of local anesthetics can result in
every 5 m inu tes, eith er vasop ressin com bined w ith ep i- clinically inap parent myonecrosis. The clinical impact of
nep hrin e or 4 m L/ kg of a 20% lip id em u lsion. Vasop res- m yotoxicity remains controversial. Most clinically relevant
sor therap y resu lted in higher coronary p erfu sion cases of myopathy and myonecrosis have been d escribed in
p ressu re d u ring CPR and higher su rvival rates as com - the setting of continuous peripheral nerve blocks, infiltra-
p ared to treatm ent w ith lip id em u lsion. These stu d ies tion of w ou nd m argins, trigger-point injections, and p erior-
su ggest that hyp oventilation and asp hyxia resu lting in bital and retrobu lbar blocks. Transient or persistent
hyp oxem ia, hyp ercarbia, and acid osis m ay blu n t or d iplopia can occur after cataract su rgery w hen perform ed
negate th e efficacy of lip id em u lsion to reverse lip op h ilic u sing a retrobu lbar or p eribu lbar nerve block. While there
d ru g-in d u ced card iac toxicity. are a nu mber of p otential mechanisms for this comp lication,
The exact m echanism of action of lip id em u lsion in the in some cases d iplopia is believed to be d ue to d irect d am-
reversal of local anesthetic toxicity is u nknow n. The tw o age to the inferior rectu s m u scle from local anesthetic (148).
m ajor p rop osed m echanism s of action are that the lip id Postarthroscopic glenohu m eral chond rolysis is a d evas-
em u lsion m ay extract lip op hilic local anesthetics from tating, noninfectiou s com p lication of arthroscop ic should er
aqu eou s p lasm a or tissu es or that it m ay counteract local surgery. In addition to radiofrequency ablation, this complica-
anesthetic inhibition of m yocard ial fatty acid oxid ation. tion is associated with intra-articular injection of bupivacaine
Other ad vantages of lipid em ulsion includ e apparent rapid via a p ain p u m p . Presu m ably, bu p ivacaine is chond rotoxic
reversal of card iotoxicity (w ithin 5 to 10 m inutes), accessi- althou gh research on this m atter is u nclear (149).
bility, and low cost. Many institu tions and organizations
have ad op ted gu id elines that incorp orate the u se of lip id
em ulsion in these cases. The use of propofol, w hich is
■ Complications of neuraxial anesthesia
form u lated in a lip id em u lsion, as an an tid ote for local N euraxial anesthesia (also know n as central neu raxial
anesthetic-ind u ced card iac toxicity is now d iscouraged blockad e) inclu d es sp inal, ep id u ral, and cau d al techniqu es.
becau se of the m yocard ial d epressant effects of propofol. These techniqu es involve d ep osition of local anesthetics,
Finally, it shou ld be noted that lipid em u lsion m ay have op ioid s, and / or other ad ju vant m ed ications in the spinal
efficacy in treating card iac toxicity from other m ed ications canal, ep id u ral sp ace, or cau d al ep id u ral sp ace. Various
includ ing, clom ip ram ine, p ropranolol, and verapam il. techniqu es m ay or m ay not u tilize a catheter for p rolonged
or continu ou s d ru g ad m inistration.
Local Anesthetic Tissue Toxicity
In ad d ition to system ic toxicity, local anesthetics (LAs) are Postdural Puncture Headache
im p licated in local inju ry to the central and p erip heral Postd u ral p u nctu re head ache (PDPH ), ocu lar d istu rbances,
nervou s system from d irect exp osu re of these tissu es to and au d itory d ifficu lties constitu te a synd rom e associated
injected form u lation. There are a variety of proposed mech- w ith cerebrosp inal flu id leak and d ecreased ICP follow ing
anism s for LA-ind u ced neu rotoxicity inclu d ing increased d u ral p u nctu re (150). The m ost p rom inent and com m on
p erm eability of the m itochond rial m em brane, collap se of sym p tom of this synd rom e is bilateral, frontal, or occipital
m itochond rial m em brane potential, and d ecrease in ad eno- head ache that is relieved w hen the p atient is su p ine. N ee-
sine trip hosphate prod u ction by either u ncoup ling of d le p enetration of the d u ra resu lts in a leak of cerebrosp inal
oxid ative p hosphorylation or inhibition of com plex I of the flu id , w hich lead s to intracranial hyp otension. Loss of cere-
m itochond rial resp iratory chain (144). Clinically, the sp inal brosp inal flu id allow s the brain to d rop cau d ad w hen the
cord and nerve roots ap p ear to be m ore p rone to the toxic p atient is u p right, resu lting in traction on the d u ra, w hich
effects of LAs than the peripheral nerves. Anim al stu d ies cau ses p ain. The size of the d efect and the incid ence of
suggest that lid ocaine and tetracaine m ay be esp ecially PDPH are related to need le gau ge, bevel d esign, orienta-
neu rotoxic in a d ose-d epend ent fashion. On the other tion of the bevel, and angle of ap p roach on insertion (151).
hand , in vitro experim ents w ith hu m an neuroblastom a cells Other factors that increase the incid ence of PDPH inclu d e
d em onstrated that bu p ivacaine and rop ivacaine had you th, fem ale sex, p regnancy, d ehyd ration, and prior his-
greater killing p otency than lid ocaine (144). Transient neu - tory of PDPH (152). The u se of sm all-gau ge, noncu tting
rologic sym p tom s (TN Ss) after spinal anesthetic likely rep - sp inal need les and refinem ent in techniqu e has red u ced the
resent a variation of LA-ind uced neu rotoxicity. incid ence of PDPH to 0.4% from 2% (153).
PDPH is usually benign and self-lim ited bu t in severe sia seem s to be related m ore to the ep id u ral ad m inistration
cases, the head ache m ay be incapacitating and treatm ent is of op ioid s than the LA.
ind icated . Many treatm ents have been proposed for PDPH
bu t the m ost effective by far is the ep id ural blood p atch, Transient Neurologic Symptoms
w hich p rovid es relief in 90% of patients after one p atch TN Ss, consisting of a back p ain or d ysesthesia w ith bilat-
(154,155). A second patch provid es relief in another 8% of eral rad iation into the bu ttocks or legs, have been d escribed
patients. The ep id ural blood patch is p erform ed by asep tias a com p lication of sp inal anesthesia, esp ecially w hen per-
cally transferring 8 to 15 m L of au tologous blood to the form ed w ith lid ocaine (150). Sym p toms begin after total
epid u ral sp ace at the level of the d ural pu nctu re. Magnetic recovery from sp inal anesthesia and w ithin 24 hours of sur-
resonance im aging of the lu m bar region after a blood p atch gery. The incid ence of this com p lication m ay be as high as
confirm s that the hem atom a cau ses a m ass effect arou nd 36% d ep end ing on the typ e of su rgery p erform ed ; the inci-
the injection site that com presses the thecal sac (156). Mass d ence is highest for p roced u res p erform ed in the lithotom y
effect w as p resent at 30 m inutes and 3 hours bu t the clot p osition and low est for those p erform ed w hile the patient
had resolved by 7 hou rs. There w as extensive extravasation is su p ine (163). Incid ence d oes not vary w ith the concentra-
of blood into the su rround ing su bcu taneous tissu es, w hich tion of lid ocaine u sed in the sp inal anesthetic (164). While
may explain the m ost com m on sid e effect of blood p atch, the etiology of TN S is not know n, m ost au thorities feel that
backache. sym p tom s are d u e p rim arily to a d irect toxic effect of the
local anesthetic. An im p ortant contribu ting factor m ay be
Backache local ischem ia from nerve stretch. The clinical im p lications
Transient m inor backache is com m on after ep id u ral (inci- of TN S are still u nclear bu t som e p ractitioners avoid u sing
d ence of 30%) and spinal anesthesia (incid ence of 21%) bu t lid ocaine for sp inal anesthetics, esp ecially if the proced u re
is not necessarily cau sally related to the anesthetic tech- w ill be p erform ed in the lithotom y p osition (157).
niqu e (157). A p rospective evalu ation of w om en fou nd that
postp artu m back pain w as associated w ith antep artu m Spinal Hematoma and Abscess
back p ain, greater w eight, and younger age (158). The inci- The m ost d read ed com p lication of neu raxial blockad e,
d ence w as essentially the sam e (45%) in w om en w ho had p arap legia from sp inal hematom a or ep id u ral abscess, is
received epid u ral anesthesias and in those w ho had not. extrem ely rare (165). Meta-analysis of d ata from large retro-
An m agnetic resonance im aging (MRI) stud y on volunteers sp ective stu d ies su ggests an incid ence of sp inal hem atom a
d em onstrated tw o p otential sou rces for back p ain in the of 1:150,000 after ep id u ral anesthesia and 1:220,000 after
lithotom y p osition, flattening of the lu m bar lord osis, and sp inal anesthesia (166). In a com p rehensive analysis of case
ad d ed tension on the lu m bosacral nerve roots (159). Seri- rep orts betw een 1906 and 1994, Vand erm eu len et al. fou nd
ou s, p rotracted back p ain is rare after central neu raxial only 61 p u blished cases of ep id u ral and / or su bd ural
blockad e and is most often d ue to traum a from need le hem atom a involving central neu raxial blockad e and 42 of
insertion. Sp inal or epid ural need les m ay inju re the these occurred in patients w ith a clotting d isord er or w ho
intraspinous ligam ent or patients m ay d evelop spasm of w ere using anticoagulants (165). Risk factors for hematoma
the p arasp inou s m uscles. Abru pt, postoperative onset of form ation follow ing neuraxial blockad e inclu d e full antico-
back p ain w ith a rad icu lar com p onent or neu rologic signs agu lation at the time of the proced ure, coagu lopathy (factor
m ay ind icate the d evelop m ent of sp inal hem atom a and d eficiency, thrombocytopenia, d isseminated intravascular
im m ed iate investigation is w arranted . coagulopathy), and d ifficult need le or catheter placem ent
(165). Ep id u ral hem atom as can occu r sp ontaneously (the
Urinary Retention m ost com mon cau se) or after d iagnostic lu m bar p u nctu re
Postoperative urinary retention is very com m on and is follow ed by anticoagu lation.
associated w ith all typ es of anesthesia and su rgery (160). The most common site for hematoma formation is the
Difficu lty in u rinating can be from any nu m ber or com bi- epidural space, presumably because of traumatic d isruption
nation of cau ses inclu d ing overd istention of the blad d er, of the epid ural venous plexus. Early symptoms includ e back
pain-ind u ced reflex spasm of the u rethral sp hincters, pain or rad icular pain but muscle w eakness may be the first
trau m a to the p elvic nerves or blad d er, and pharm acologic com plaint (165). Neurologic symptoms of low er extremity
effects. It is m ore com m on in eld erly m en and in p atients w eakness and bow el and blad d er d ysfunction d evelop once
receiving op iates (161). In a large review of published stu d - enough blood has accumulated to create a mass effect and
ies of u rinary retention in inguinal hernia surgery, the com press the spinal cord or nerve roots. Vigilance, regular
authors fou nd that the incid ence is low er w ith local anes- neurologic assessment, and exped itious d iagnostic stud ies
thesia (0.4%) than w ith regional (2.4%) or general (3.0%) are necessary to detect spinal hematoma early enough to
(162). Sp inal anesthesia rapid ly elim inates the m ictu rition avoid permanent neurologic d amage. Recovery of neuro-
reflex and it d oes not retu rn u ntil after m otor and m ost sen- logic function is possible if decompressive laminectomy is
sory fu nction has recovered . Patients shou ld be monitored performed w ithin 8 hours of the onset of paraplegia.
for retu rn of blad d er fu nction, especially w ith long-acting The reported incid ence of epid u ral abscess in neu raxial
local anesthetics. Urinary retention after epid u ral anesthe- anesthesia varies w id ely d ep end ing on the stu d y m ethod
bu t is generally low, betw een 1 in 2000 and 1 in 5000 root and the spinal cord accounted for 16% and 13% of
catheters (167,168). Like spontaneou s spinal hem atom a, closed claims related to nerve injuries, respectively, in the
ep id u ral abscess is m ore com m only rep orted from sou rces ASA’s Closed Claims Project (176). In a prospective, multi-
not related to ep id u ral or spinal anesthesia. Abscess form a- center stud y of serious complications of regional anesthesia,
tion related to neuraxial blockad e is believed to be d ue to Auroy et al. fou nd a low incid ence of rad iculopathy follow -
introd u ction of bacterem ic blood into the ep id u ral sp ace. ing spinal and epid u ral anesthesia (175). N eed le insertion
Risk factors for infection and abscess form ation inclu d e or d rug injection w as associated w ith pain or paresthesias
im m unosu p p ression, bacterem ia, caud al anesthesia, and in m ost cases. In contrast to the m id line approach, the para-
breaks in asep tic techniqu e. One recent survey of ep id u ral med ian (oblique lateral) approach to the epid ural and sub-
abscesses fou nd that half of incid ents w ere associated w ith arachnoid sp ace d irects the need le tow ard the d u ral cu ff
low m olecu lar w eight heparin (LMWH ) therapy (168). In region of the nerve root, increasing the risk of injury.
ad d ition to back p ain and neu rological symp tom s, p atients Reynold s reported on a cluster of seven cases w ith per-
w ith ep id u ral abscess usu ally present w ith fever, leu kocy- sistent u nilateral sensory loss, foot d rop , and urinary
tosis, m eningeal signs, and signs of localized infection. N ot sym p tom s (three p atients) follow ing sp inal or com bined
surp risingly, Staphylococcus aureus w as the m ost com m on sp inal-ep id u ral anesthesia. All had a p ainfu l lu m bar pu nc-
etiologic agent in one large series (167). Once the d iagnosis tu re and six had MRI show ing a syrinx in the conu s. The
has been established , prom pt therap y w ith antibiotics and au thors p ointed ou t that the term ination of the conu s is
surgical evacuation should be p erform ed in ord er to m axi- variable and em p hasized the im p ortance of p erform ing the
m ize the likelihood of neu rologic recovery. lu m bar p u nctu re at the correct level (177).
Anticoagulation and Neuraxial Blockade Spinal Cord Ischemia

A nu m ber of large case series in a variety of op erative set- The anterior portion of the sp inal cord is supp lied by the
tings have established the safety of system ic anticoagu la- anterior sp inal artery, w hich has p oor vertical anastom otic
tion follow ing neu raxial blockad e in select patients u sing connections betw een rad icu lar branches that su p p ly it. The
strict gu id elines (153,169). In general, p atients w ithou t p re- anterior sp inal cord is su scep tible to ischem ic injury if the
existing coagu lop athy can receive IV heparin 60 m inu tes segm ental blood supp ly is com prom ised either through
follow ing atrau m atic insertion of an ep id u ral catheter trau m a or d u e to system ic reasons. The anterior sp inal
w ithou t significant risk of hem atom a. On the other hand , artery synd rome is characterized by a d ense motor p araly-
there is an increased risk for sp inal hem atom a in those sis, variable sensory im p airm ent, and p reservation of posi-
p atients w here there w as less than a 60-m inu te time inter- tion and vibratory sense. Inju ry to the anterior sp inal artery
val betw een the ad m inistration of heparin and lum bar has been rep orted w ith ep id u ral catheter or need le p lace-
p unctu re, trau m atic need le placement, and concom itant m ent bu t su rgical d isru p tion of the blood su p p ly and / or
u se of other anticoagulants (aspirin). In ad d ition, there system ic hyp otension is m u ch more likely a cau se (178).
have been nu m erou s rep orts of sp inal hem atom a d evelop -
ing after sp inal or ep id u ral anesthesia in patients receiving Bradycardia, Hypotension, and Cardiac Arrest
LMWH for perioperative thromboprophylaxis (166,170,171). H yp otension is extrem ely com m on d u ring neu raxial
Most of these cases involved epid ural anesthesia and som e anesthesia and is better regard ed as a sid e effect than a
w ere related to rem oval of the epid u ral catheter w hile com p lication. H yp otension resu lts from the p reganglionic
receiving LMWH (172). The risk of fatal pu lm onary em bo- sym pathetic block that red uces system ic vascu lar resist-
lu s w ithou t p rop hylaxis is greater than the risk of sp inal ance and increases venod ilation. Decreased venous return
hem atom a bu t that d oes not m ean that effective throm bo- enhances vagal tone. H igh symp athectom y also resu lts in
p rophylaxis takes p reced ence over, and exclu d es, regional brad ycard ia throu gh blockad e of the card iac accelerator
anesthesia (173). A consensus statem ent from the ASRA fibers, w hich arise from sp inal levels T1 to T4. Decreased
states that spinal or epid u ral anesthesia can be ad m inis- venou s retu rn, system ic hyp otension and brad ycard ia can
tered in the setting of heparinization or LMWH ad m inis- red u ce card iac ou tp u t. Mod erate and severe brad ycard ia
tration as long as certain p recautions are heed ed (174). A occu rs in abou t 10% and 1% of neu raxial anesthetics,
com p lete d escrip tion of the cu rrent recom m end ations for resp ectively, and can d evelop at any tim e d u ring the anes-
evalu ating and m anaging p atients for regional anesthesia thetic (179). Risk factors for the d evelop m ent of hypoten-
w hile receiving antithrom botic or throm bolytic therapy is sion and brad ycard ia d u ring sp inal and epid u ral anesthesia
available on the ASRA w eb site. have been id entified in large-scale p rosp ective stu d ies
(Table 12.9) (180,181).
Nerve Injury In the 1980s, review of closed insurance claims revealed a
Several large retrospective stu d ies have confirm ed that per- set of cases involving cardiac arrest during spinal anesthesia
manent injury to the spinal cord or nerve roots is very in otherw ise healthy patients (182). The outcome in these
uncommon (175). The most common neurologic complica- cases was catastrophic; most patients died or had severe
tion of central blockad e is d am age to a nerve root from nee- neurologic injury. Further evaluation of these cases sug-
d le or catheter placem ent. Injury to the lu m bosacral nerve gested that sed ation and respiratory insufficiency might
Table 1 2 .9 Risk fa ct or s for br a dyca rd ia a n d hyp ot en sion d u r in g cen t ra l n eu ra xia l block a d e

Technique Risk Factors for Hypotension Risk Factors for Bradycardia
Epidural anesthesia • Epidural fentanyl • Female sex
• Increased spread of sensory blockade • Use of tourniquet
• Lack of tourniquet use
• Use of carbonated lidocaine
Spinal Anesthesia • Sensory block higher than the fifth thoracic dermatome • Baseline heart rate less than 60 beats/min
• Age older than 40 years • ASA physical status I
• Baseline systolic blood pressure less than 120 mm Hg • Use of beta-adrenergic blocking agents
• Use of combined spinal and general anesthesia • Sensory block higher than the fifth thoracic dermatome
• Dural puncture cephalad to the L2–L3 interspace
• Addition of phenylephrine to the local anesthetic spinal block
have contributed to the card iac arrest. Card iopulmonary p ressu re on the p lu nger of a syringe. This end point is su b-
resuscitation in these w itnessed card iac arrests might have ject to m isinterp retation. Even w ith the visu al clues of
been ineffective d ue to the sympathetic blockad e d uring sp inal techniqu e (retu rn of cerebrosp inal flu id ), failu res
high spinal anesthesia and d elayed ad ministration of potent occu r in 4% to 17% of sp inal anesthetics. The other extrem e
vasoconstrictors. In large, prospective surveys of complica- is total spinal anesthesia w hen an excessive d ose of local
tions of regional anesthesia, card iac arrest during spinal anesthetic is d elivered into the su barachnoid or subd ural
anesthesia occurred w ith an incid ence of 2.7 to 7.0 per 10,000 sp ace. Patients are rend ered ap neic, u nconsciou s, and
(175,183,184). The incidence of card iac arrest during spinal hyp otensive and requ ire intu bation, m echanical ventila-
anesthesia is higher than that seen w ith GA and epid ural tion, and vasop ressor su p p ort.
anesthesia. Survivors of card iac arrest w ere younger and
w ere healthier as measured by ASA classification. Sedation,
respiratory insufficiency, and especially severe brad ycard ia ■ MISCELLANEOUS COMPLICATIONS
have been implicated as m ajor contributing factors to car- OF ANESTHESIA
d iac arrest. Studies in human volunteers given spinal anes-
thetics have show n that hypovolemia potentiates the vagally
■ Postoperative nausea and vomiting
mediated bradycardia and can even precipitate cardiac Postoperative nau sea and vom iting (PON V) is anesthesiol-
arrest (184). Other cases of brad ycard ia and card iac arrest ogy’s “big little p roblem ” and a great d eal of effort is
d uring spinal anesthesia have occurred after the ad d ition of focu sed on strategies to red u ce the frequ ency of this p rob-
potent vasod ilators such as sod ium nitroprussid e. Stud ies in lem . N au sea is an u np leasant sensation in the epigastrium
d ogs show that spinal anesthesia suppresses the cate- that is associated w ith an u rge to vom it w hile vom iting is
cholamine response to cardiac arrest and reduces the coro- the forcefu l exp u lsion of gastric contents. The incid ence of
nary perfusion pressure (CPP) that is obtained d uring CPR nau sea and vom iting varies d ep end ing on the p atient p op -
(185,186). The CCP achieved d uring CPR in spinal anes- u lation and setting bu t generally affects 10% of patients in
thetized dogs w as significantly below the threshold for pre- the p ostop erative anesthesia care u nit (PACU) and 30% of
d icting successful resuscitation, and relatively high doses p atients d u ring the first 24 hou rs (187) (Fig. 12.5).
(0.1 mg/ kg) of epinephrine were required to restore CPP Vomiting is controlled by emetic centers that receive
(185). These stud ies help to explain why CPR may be ineffec- afferent inpu t from many sou rces insid e and outsid e the
tive in patients suffering cardiac arrest during spinal anes- CN S. A major inp ut is from the chemoreceptor trigger zone.
thesia and they suggest that high doses of vasopressors Structu res involved in vom iting are rich in d opam inergic,
(epinephrine, norepinephrine, and/ or vasopressin) may be muscarinic, serotonergic, histaminic, and opioid receptors,
required to restore CPP d uring CPR. In summ ary, severe w hich explains the basic ap proach of antagonizing variou s
brad ycard ia w ith hypotension should be treated rapid ly neurotransmitter receptors in ord er to control vomiting.
w ith volume infusion, atropine, and vasopressors, prefer- Recently, a multidisciplinary panel of experts published
ably epinephrine (184). If card iac arrest d evelops, CPR consensus guidelines on PONV based on a structured review
should be accompanied by early and aggressive administra- of the medical literature (188). A great deal of useful informa-
tion of vasopressors. tion can be d raw n from the conclusions reached by the expert
panel and other authors who have reviewed this topic (187).
Failed Block A variety of factors are suspected to influence the occurrence
Perhaps one of the m ost frequent “com p lications” of of PONV includ ing patient characteristics, site of surgery,
regional anesthesia is failure of the blockad e. Entry into the d uration of surgery, and type of anesthetic. A combination of
ep id u ral sp ace is confirm ed by tactile loss of resistance to factors may contribute to the occurrence of nausea, vomiting,
FIGURE 12.5. Algorithm for the

management of postoperative nausea Evaluate Ris k o f PONV in S urg ic al Patie nt
and vomiting. (Reprinted with permis-
sion from Gan TJ , Meyer T, Apfel CC,
et al. Consensus guidelines for man-
aging postoperative nausea and vom-
iting. Anesth Analg 2003;97(1):62–71.)
Lo w Mo de rate Hig h
No pro phylaxis
unle s s the re is Co ns ide r re g io nal ane s the s ia
ris k o f me dic al
s e que lae fro m
vo miting
No t Indic ate d
If g e ne ral ane s the s ia is us e d, re duc e bas e line

ris k fac to rs and c o ns ide r us ing no npharmac o lo g ic
the rapie s
Patie nts at Patie nts at

mo de rate ris k hig h ris k
Co ns ide r antie me tic

Initiate c o mbinatio n
pro phylaxis with
the rapy with 2 o r 3
mo no the rapy (adults ) o r
pro phylac tic ag e nts fro m
c o mbinatio n the rapy
diffe re nt clas s e s
(c hildre n and adults )
or both. For example, volatile anesthetics appear to be the simplified risk score based on identifying four primary risk
most important cause of early vomiting in both children and factors: female sex, nonsmoking status, history of PONV, and
adults but late vomiting seems to be d ue to postoperative opioid use (191). The incidence of PONV increases with the
opioids (189). The guidelines stress identifying patients at presence of one or more of these risk factors.
high risk for PONV. Risk factors for PONV in adults include Strategies to red u ce the baseline risk of PON V are listed
female sex, nonsmoking status, a history of PONV or motion in Table 12.10. There is no single “m agic bu llet” and the
sickness, duration of surgery, type of surgery (laparoscopy, m ost effective strategy m ay be one that encom p asses m any
ear-nose-throat, neurosurgery, breast, strabismus, laparotomy, or all of the method s listed . In certain high-risk p atients, a
plastic surgery), use of volatile anesthetics, use of nitrous m u ltimod al ap p roach consisting of anxiolysis, hyd ration,
oxide, and use of opioids. Risk factors in children are similar su p p lem ental oxygen, p rop hylactic antiem etics, total IV
to adults with the follow ing differences, vomiting is twice as anesthesia w ithou t nitrou s oxid e, and ketorolac, m ay be
frequent in children, the risk increases as children age but effective. The consensu s gu id elines su ggest antiem etic
decreases after puberty and sex differences are not seen therap y for p rop hylaxis in p atients at m od erate or high
before puberty. Surprisingly, smoking protects against PONV, risk of PON V. There is no d ifference in the efficacy and
perhaps throu gh increased clearance of anesthetic d ru gs safety p rofiles of the variou s serotonin (5-H T3) recep tor
d ue to enzyme ind uction (190). Apfel et al. have created a antagonists in the p rop hylaxis of PON V. These d rugs have
Table 1 2 . 1 0 St ra t egies t o r ed u ce ba selin e r isk of A BMI of 25 kg/ m is norm al w hile a p erson w ith a
p ost op era t ive n a u sea a n d vom it in g BMI of 25 to 30 kg/ m is overw eight. Persons w ith a BMI of
30, 35, and 55 kg/ m are consid ered obese, morbid ly
Use regional anesthesia instead of general anesthesia obese, and su p er-m orbid ly obese, resp ectively, and have an
Use propofol for induction and maintenance of anesthesia increased risk of m ed ical com plications and increased m or-
tality. Physiologic changes associated w ith obesity and
Intra-operative supplemental oxygen
m orbid obesity lead to an increased incid ence of com orbid
Adequate hydration cond itions, su ch as gall blad d er d isease, d iabetes, hyper-
Avoid nitrous oxide tension, heart d isease, osteoarthritis, and obstru ctive sleep
Avoid volatile anesthetics ap nea (OSA) (195). Persons w ith a BMI 30 have an
increased rate of m ortality especially if they have an
Minimize intra-operative and postoperative opioids
and roid (central or m ale) p attern of fat d istribu tion or
Minimize or eliminate use of neostigmine rap id w eight gain after age 20.
Many of the p athop hysiologic changes in obesity com -
bine to increase the risk of com p lications d u ring ind u ction
of anesthesia, m aintenance of the airw ay, m ask ventilation,
a favorable sid e effect profile; the m ost com m on p roblem s
intu bation and extu bation. A fat face and cheeks, a fat,
are head ache, constipation, and increased liver fu nction
short neck, large tongue, excess pharyngeal tissue, restricted
tests. To be m ost effective, 5-H T3 recep tor antagonists, like
m ou th op ening, and large breasts m ay m ake m ask ventila-
ond ansetron, shou ld be given at the end of surgery. Sm all
tion and intu bation d ifficu lt or im p ossible. Mask ventila-
d oses of d exam ethasone (2.5 to 5 mg) are effective in red u c-
tion and intu bation are also d ifficu lt in m any p atients w ith
ing PON V w hen given prior to ind u ction of anesthesia.
OSA. While only 5% of m orbid ly obese p atients have OSA,
Althou gh ad verse events have not been reported in
the m ajority of p atients w ith OSA are obese (196). In obese
hu m ans after a single bolu s d ose of d exam ethasone, there
p atients w ith OSA, the p haryngeal area is red uced d ue to
is som e evid ence that a single d ose can im p air w ou nd
d ep osition of fat in the p haryngeal tissu es and the airw ay is
healing in rats (192). Droperid ol is equally effective as
com p ressed externally by fat m asses in the su p erficial neck
ond ansetron for prop hylaxis of PON V and , like the 5-H T3
area. All central d ep ressants and m u scle relaxants w ill pro-
recep tor antagonists, is m ost effective w hen given at the
m ote p haryngeal collap se in obese p atients w ith OSA by
end of su rgery. The Food and Drug Ad m inistration (FDA)
d im inishing the action of the p haryngeal d ilator m u scles.
has issu ed a “black box” w arning that d roperid ol m ay
Thu s, obese p atients w ith or w ithou t OSA are at risk of air-
cau se d eath or life-threatening events associated w ith QT
w ay obstru ction w hen given sed atives, anesthetics, or
prolongation and torsad e d e pointes bu t the w arning is not
m u scle relaxants. In a retrosp ective stu d y of p atients being
w ell su bstantiated by the m ed ical literatu re. The exp ert
su rgically treated for OSA, the com p lication rate w as 13%.
panel au thoring the consensus guid elines expressed con-
Seventy-seven p ercent of these com p lications w ere airw ay
sid erable concern abou t the valid ity of the FDA w arning.
p roblem s (197). Patients w ith p roblem s w ith intu bation
Im p ortantly, m etoclop ram id e is not effective for PON V
w ere heavier w hile p atients exp eriencing p roblem s follow -
prop hylaxis and has consid erable sid e effects. Antiem etics
ing extu bation had received m ore narcotic analgesia.
shou ld be given to those p atients w ho d evelop PON V and
It is commonly believed that obese patients have increased
w ere not given p rop hylaxis or in w hom p rop hylaxis failed .
intragastric volumes, increased intra-abdominal pressures,
Treatm ent d oses of the 5-H T3 receptor antagonists are one
increased incidence of hiatal hernia, and increased incid ence
qu arter of those u sed for prophylaxis. In those patients fail-
of gastroesophageal reflux, all of w hich may put them at
ing p rop hylaxis, d ru gs u sed to treat PON V should be from
higher risk of gastric regurgitation and aspiration d uring
another class than the d rugs used for prophylaxis. Interest-
mask ventilation, intu bation and extu bation. Difficult mask
ingly, a sm all, su bhypnotic d ose of propofol (20 m g) is
ventilation m ay resu lt in gastric insu fflation, w hich further
effective in treating PON V (193).
increases the risk of regu rgitation and aspiration. Althou gh
the evid ence for these risk factors is conflicting, m any
■ Obesity and morbid obesity au thors recommend taking rou tine p recau tions to p revent
acid aspiration in obese patients (194).
Obesity has now reached ep id em ic p rop ortions in the
In a large m u lticenter stu d y of ad verse ou tcom es after
United States and the health concerns of an obese popula-
GA, obesity w as one of several p red ictors of severe respira-
tion are being ad d ressed in the lay p ress as w ell as the m ed -
tory ou tcom es (198). Obesity cau ses abnorm alities of both
ical literature (194). The body mass ind ex (BMI) is a measure
lu ng volum es and gas exchange that are exacerbated by the
of the relationship betw een height and w eight and it is cal-
su p ine p osition and anesthesia. Fu nctional resid ual capac-
cu lated by the form ula:
ity (FRC) and expiratory reserve volu m e (ERV) are red uced
so that tid al volu m e m ay occu r at or below closing cap acity
bod y w eight (in kg) lead ing to closu re of sm all airw ays, ventilation-p erfusion
BMI
height 2 (in m eters) mismatching, atelectasis, and arterial d esaturation (194,199).
Pelosi et al. stu d ied the effects of BMI on respiratory fu nc- severely obese, and , w ith the excep tion of su perficial
tion d u ring anesthesia in 24 patients (8 norm al w eight w ou nd infections and atrial d ysrhythm ias, obesity w as not
p atients, 8 m od erately obese patients, and 8 m orbid ly a significant m u ltivariate risk factor for ad verse ou tcom es
obese p atients) (199). With increasing BMI, there w as an (202). In a sim ilar stu d y, Fasol et al. fou nd that there w as no
exponential d ecline in FRC, an exponential d ecline in com - d ifference in op erative m ortality betw een obese and
p liance of the resp iratory system , an increase in resistance, nonobese card iac su rgery p atients, bu t the form er had
an exp onential d ecline in the oxygenation ind ex (PaO 2/ higher rates of infection, sternal d ehiscence, arrhythm ias,
PAO 2) and an increase in the w ork of breathing (199). and myocard ial infarction (203). Choban and Flancbaum
Increased basal m etabolic rate and high resting oxygen review ed the literatu re for a nu m ber of elective su rgical
consum p tion d ecreased FRC and altered oxygenation p roced u res and conclu d ed that there w as only a m od est
w ork in com bination to d rastically red uce the tim e it takes increase in p eriop erative com p lications, and these w ere
obese p atients to d esatu rate d u ring period s of hypoventila- mostly w ou nd p roblem s (201). Mortality w as not increased
tion or ap nea. In general, obese p atients d esaturate rap id ly and op erative resu lts w ere not ad versely affected . On the
after ind u ction of anesthesia d esp ite preoxygenation. In other hand , obese p atients had higher morbid ity and m or-
sum mary, m orbid ly obese p atients m ay be very d ifficu lt to tality follow ing trau m a and bu rn su rgery.
ventilate by m ask, prone to rapid d esaturation d u ring
ap neic p eriod s, d ifficu lt to intubate, and be at increased
risk of acid asp iration. Therefore, m any authorities recom -
■ Hypothermia
m end aw ake fiberop tic intu bation for GA (194). Desatu ra- While the hu m an therm oregu latory system norm ally
tion d u e to atelectasis d uring GA and m echanical m aintains a core bod y tem p eratu re near 37 C, anesthesia
ventilation is better treated w ith m od erate levels of PEEP and exp osu re to a cold environm ent often resu lt in periop-
than w ith excessive tid al volu m es. erative hyp otherm ia. H yp otherm ia has been im p licated as
Obese p atients are prone to hypertension, and obesity is an im p ortant factor in nu m erou s p eriop erative com plica-
recognized as an ind epend ent risk factor for ischem ic heart tions inclu d ing coagu lop athy, su rgical w ou nd infection,
d isease, esp ecially in patients w ith a central, and roid d istri- and card iac m orbid ity (204). A nu m ber of afferent receptors
bu tion of fat. Obesity-ind u ced card iom yopathy refers to a throu ghou t the bod y term inate in the CN S, w hich nor-
cond ition w here volu m e and p ressu re overload lead to m ally resp ond s to sm all variations in temp eratu re to m ain-
heart failu re, w hich is often biventricular. Increased blood tain therm al hom eostasis w ithin a narrow range. Besid es
volume and high card iac ou tp ut resu lt in left ventricu lar obviou s behavioral resp onse to changes in tem perature,
enlargem ent and increased w all stress. Persistent, abnor- effector resp onses to cold inclu d e vasoconstriction and
m ally high w all stress p rom otes the d evelop m ent of eccen- shivering w hile effector responses to w arm th inclu d e cuta-
tric hyp ertrop hy, w hich resu lts in left ventricular (LV) neou s vasod ilation and sw eating. N orm ally, the threshold
systolic d ysfu nction, d iastolic d ysfu nction, and clinical for resp onse to w arm th is narrow ly m aintained only 0.2 C
heart failu re. Pu lm onary hypertension second ary to OSA above the resp onse to cold . Therm oregu latory vasocon-
m ay cau se right ventricular enlargem ent, hypertrop hy, and striction and vasod ilation occurs in arteriovenou s shunts
failu re, as w ell. In an au topsy stu d y of m orbid ly obese located p rim arily in the fingers and toes.
p atients d ying of su d d en card iac d eath, 10 of 22 p atients GA and muscle relaxants abolish the most important
had d ilated card iom yopathy, six had severe coronary behavioral responses to perturbations in temperature, and
artery d isease, and fou r had LV hypertrop hy w ithou t d ila- they also prevent shivering (205). GA, opioids, and IV anes-
tion (200). thetics low er the threshold for cold responses and w iden the
Finally, obese patients m ay present challenges w ith range of temperatures where thermoregulatory responses
respect to IV access, patient positioning, m onitoring, and are not triggered . Thus, anesthesia d ecreases the patient’s
regional anesthesia. For exam ple, noninvasive blood pres- response to cold and rend ers the patient poikilothermic over
sure cu ffs often d o not fit p roperly even if they are large size an extend ed range of temperatures (∼4 C). During the first
and it m ay be d ifficult or im possible to obtain an accu rate hour of GA, core temperature d rops by 1 to 5 C resulting
blood pressure read ing w ithout d irect arterial cannulation. from redistribution of body heat from the core to the periph-
Ind ep end ent of ad d itional com orbid cond itions, the ery d ue to opening of peripheral arteriovenous shunts. After
p hysical state of obesity im p lies that patients are at the first hour, temperature continues to decline due to loss of
increased risk of p eriop erative com p lications becau se of bod y heat in excess of metabolic prod uction, although at a
their excess w eight and obese bod y habitus although there slow er rate. Most heat is lost through the skin by convection.
are few stu d ies available to establish the precise im p act of The core temperature stops declining after 3 to 5 hours. This
obesity on anesthesia and surgery (201). Of the stu d ies that thermal plateau, or steady state, may be secondary to effec-
have looked at the qu estion of w hether or not obesity is an tive insulation or w arming measures, or it may be due to
ind epend ent risk factor for ad verse ou tcom es after su rgery, intense thermoregulatory vasoconstriction in patients not
few actu ally confirm any ad d itional serious risk. In a m u lti- w ell protected against heat loss.
variate single center stud y of 2299 patients u nd ergoing car- H yp otherm ia affects p atients w ho receive ep id u ral or
d iac su rgery, 25% of patients w ere obese and 13% w ere sp inal anesthesia as w ell (205). Regional anesthesia blocks
afferent and efferent neu ral com ponents of the therm oreg- Table 1 2 .1 1 D iffer en t ia l d ia gn osis of in t ra -
u latory resp onse. Regional anesthesia has a su rprising cen- op era t ive hyp er t h er m ia
tral effect on therm oregulation, also, so that the CN S
erroneously jud ges the skin tem perature in blocked areas 1. Iatrogenic causes
to be abnorm ally high. Und etected hypotherm ia is rela- a. Active warming of patients (particularly pediatric patients)
tively com m on d uring spinal or ep id ural anesthesia b. Application of tourniquets to upper or lower extremities for
because patients feel w arm er and anesthetists seld om prolonged periods of time (especially in children)
c. Injection of sclerosing solutions into arteriovenous malformations
m onitor tem p eratu re d u ring regional anesthesia.
d. Long procedures where patient is mostly covered with drapes
H ypothermia is used to protect the heart and CNS from
2. Hyperthermia secondary to diseases
potential periods of ischemia during cardiac surgery and a. Thyrotoxicosis and thyroid storm
neurosurgery. On the other hand , mild hypothermia red uces b. Riley-Day syndrome (dopamine -hydroxylase deficiency)
the resistance to w ound infection by decreasing cutaneous c. Osteogenesis imperfecta
blood flow and impairing immune function. Maintenance of d. Central nervous system dysfunction (status epilepticus, hypoxic
normothermia has been show n to red uce the incid ence of encephalopathy)
w ound infections in patients und ergoing colon resection e. Infectious agents (surgical manipulation of infected tissue, head
(206). H ypothermia impairs platelet function and hind ers trauma, prolonged surgery on urinary tract)
activation of the coagulation cascade resulting in coagulopa- 3. Drug-induced hyperthermia
thy, increased blood loss, and increased need for blood trans- a. Malignant hyperthermia
b. Neuroleptic malignant syndrome
fusion (207). The incid ence of ventricular dysrhythmias and
card iac morbid ity is increased by hypothermia. Decreased
metabolism and clearance of d rugs can prolong postopera-
tive recovery (204).
N orm otherm ia is best m aintained u sing a variety of Malignant Hyperthermia
m easu res to p revent heat loss and actively w arm the Malignant hyp ertherm ia is a seriou s cond ition that d evel-
patient (204). Both cold blood and room -tem peratu re IV op s in genetically p red isp osed p atients w ho are exp osed
flu id can significantly d ecrease bod y tem peratu re and , to certain “triggering agents,” namely the PIAs and / or
w hen given in large am ounts, these flu id s shou ld be su ccinylcholine. N onsp ecific signs and sym p tom s of
w arm ed to p revent fu rther d ecline in temp eratu re. Warm - m alignant hyp ertherm ia inclu d e tachycard ia, tachypnea,
ing these flu id s, how ever, w ill not actively increase a d iap horesis, and fever. More sp ecific signs inclu d e skeletal
patient’s bod y tem peratu re. Skin is the m ajor sou rce of heat m u scle rigid ity, m yoglobinu ria, m yoglobinem ia, hyper-
loss and increasing the am bient tem peratu re w ill red uce kalemia, hypercalcemia, and mixed acid osis (209). The most
convective heat losses. Forced air w arm ing blankets can sensitive indicator of potential malignant hyperthermia is an
also p revent convective losses. In ad d ition, forced air unanticipated increase (e.g., d oubling or tripling) of the end -
w arm ing is the m ost effective m ethod of actively w arm ing tid al CO 2 concentration w hile minute ventilation is kept con-
a p atient. Desp ite som e concerns about the increased tu r- stant. While the exact cause of malignant hypothermia is not
bu lent airflow created by these w arm ing d evices, they d o know n, the p ivotal role of increased intracellu lar calciu m
not ap p ear to increase the risk of infections; in fact, these is w ell established (210). The consequ ences of increased
d evices m ay red u ce the incid ence of w ou nd infections intracellu lar calciu m inclu d e activation of ATPases w ith
(206). Skin is relatively vu lnerable to injury from heat esp e- d ep letion of adenosine triphosphate (ATP), actin-myosin
cially w hen p ressu re is applied to the skin. Circu lating- interaction causing muscle contraction, consumption of glu-
w ater m attresses are relatively ineffective in w arm ing the cose, glycogen and oxygen, and generation of heat. As ATP
patient and can be a source of p ressu re-therm al inju ry. is d epleted , membrane integrity is compromised and potas-
Patients at the extrem es of age, w ho are d ebilitated , and / or sium, myoglobin, creatine kinase, and tissue thromboplastin
w ho are u nd ergoing major operations, m ay be esp ecially at are released extracellularly. The treatment of malignant
risk of bu rns from circu lating-w ater m attresses (208). hyperthermia is outlined in Table 12.12.
■ Hyperthermia
■ Anaphylactic and anaphylactoid reactions
There are nu m erou s causes of perioperative hypertherm ia,
in the perioperative period
and increased bod y tem perature m ay be d ue to iatrogenic
cau ses or it m ay be second ary to any one of a nu m ber of Unfortu nately, allergic reactions are one of the m ajor fac-
d iseases (209). A list of etiologies appears in Table 12.11. tors contribu ting to m orbid ity and m ortality d uring anes-
Iatrogenic intra-operative hyp ertherm ia m ay occu r d u ring thesia (211). Of the variou s typ es of allergic reactions,
long proced u res w here the patient is alm ost com p letely anap hylactic and anap hylactoid reactions are the m ost
covered by su rgical d rap es and the op erative area is sm all. seriou s. This top ic has been review ed recently in the
Excessive active w arm ing can cau se m ild hyp ertherm ia, anesthesiology literatu re (212,213). Anap hylaxis is an
especially in ped iatric patients. im m u ne-m ed iated allergic reaction and u su ally occu rs on
Table 1 2 . 1 2 Su ggest ed t r ea t m en t of m a lign a n t hyp er t h er m ia (M H )

• Call for experienced help.
• Stop potent inhaled agents and succinylcholine.
• Hyperventilate with 100% oxygen at two to three times the predicted minute ventilation.
• Prepare and administer IVdantrolene 2.5 mg/kg. Repeat as often as necessary to control clinical signs of MH.
• Treat acidosis with sodium bicarbonate.
• Avoid calcium channel blockers. Treat arrhythmias with other medications as needed.
• Obtain blood gases, electrolytes, creatine kinase (CK), blood, and urine for myoglobin, coagulation profile.
Measure CKs every 6 hours until decreased. Follow coagulation profile to monitor for disseminated intravascular
coagulation (DIC).
• Treat hyperkalemia with glucose, insulin, and calcium.
• Monitor core temperature and begin cooling measures, if hyperthermic (nasogastric lavage, rectal lavage and/or
surface cooling). Avoid over cooling.
• Continue intravenous dantrolene for at least 24 hours after control of the episode (approximately 1 mg/kg
q 6 hours). Continue dantrolene administration for at least 36 hours after an event. Watch for recrudescence by
monitoring in an ICU for at least 24 hours.
• Ensure adequate urine output by hydration and diuretics.
• Report patients who have had acute MH episodes to the North American MH Registry of the Malignant
Hyperthermia Association of the United States: 1-412-692-5464
For consultation to help with patient management, call the MH Hotline: 1-800-MH-HYPER (1-800-644-9737) or 1-315-464-7079 if
outside the United States.
reexp osu re to a sp ecific antigen bu t can occu r on first The m ost frequ ent class of anesthetic m ed ications caus-
exp osu re. The reaction involves (Ig)E-m ed iated release of ing anaphylaxis is the m u scle relaxants w ith an estim ated
p ro-inflam m atory m ed iators (histam ine, prostacyclin, leu - incid ence of 1 in 6,500 ad m inistrations of N MBAs (215).
kotrienes) from m ast cells and basophils. H istam ine acts on Even p atients w ho have never been exp osed to N MBAs can
type 1 recep tors to increase m u cus prod u ction, increase have an allergic reaction to these m ed ications. Recent w ork
heart rate, and cau se flu shing. Typ e 2 recep tors are resp on- has im plicated the qu aternary am m onium ion as the aller-
sible for increasing vascu lar p erm eability, increasing gas- genic d eterm inant in N MBAs. A nu m ber of m ed icines and
tric acid secretion and airw ay mucus production. H istam ine com m only u sed chem icals, su ch as toothp astes, d etergents,
and other inflam m atory m ed iators increase the prod u ction sham p oos, and cou gh m ed icines, share these d eterm inants
of nitric oxid e. Prostagland ins and leu kotriene recep tors w ith N MBAs and m ay accou nt for allergic reactions in
are present in bronchial sm ooth m uscle, the skin, and the p atients not p reviou sly exp osed to the d ru g (213,216).
vascu lar bed . Activation of these receptors causes bron- N atural rubber latex is the second m ost comm on cause fol-
choconstriction, cu taneou s w heal, and increased vascu lar low ed by antibiotics and anesthetic ind u ction agents. Du r-
p erm eability. Anap hylactoid reactions are d u e to nonim - ing card iac su rgery, p atients are exp osed to large d oses of a
m u ne release of inflam m atory m ed iators and are clinically variety of antigenic m ed ications inclu d ing hep arin, p rota-
ind istingu ishable from anap hylactic reactions. mine, and occasionally ap rotinin. Yet, antibiotics, m u scle
Anap hylaxis is an u nanticipated , severe allergic reac- relaxants, and blood p rod u cts accou nt for the m ajority of
tion m anifested by card iovascu lar sym ptom s (tachycard ia, allergic reactions d u ring card iac cases (217). Table 12.13
hypotension, shock), cutaneou s sym ptom s (urticaria, review s a nu m ber of m ed ications u sed in the p eriop erative
flushing, p ru ritu s, angioed em a), and respiratory sym p - p eriod and their allergic reactions.
tom s (bronchosp asm , w heezing, d yspnea, hyp oxem ia). In N atural rubber latex is a ubiquitous material found in a
rare cases, acu te coronary events can occu r in conju nction w id e variety of m ed ical prod ucts, although latex-free alter-
w ith a hyp ersensitivity reaction, a cond ition referred to as natives are becom ing m ore w id ely available. Exp and ing u se
Kou nis synd rom e, allergic angina, or allergic m yocard ial of universal precautions has led to an increase in the use of
infarction (214). Perioperative anaphylaxis can occu r gloves containing latex. This high d emand for gloves
w ithin m inutes of exp osu re to the offend ing m ed ication or resulted in rapid manufacture of prod ucts w ith increased
com pou nd , w hich is often a m ed ication given d u ring protein content, w hich led to an increase in the incid ence of
ind uction of anesthesia. In the patient covered by d rap es latex anap hylaxis (218). Recent improvements in latex pro-
w ith GA alread y w ell und erw ay, the early cu taneous signs d uction and the increased use of low -protein, pow d er-free
m ay be overlooked and the d iagnosis can be d elayed or gloves have red u ced the incid ence of reactions. N ot all reac-
m issed . In ad d ition, atypical presentations have been tions to latex are anap hylactic in natu re. The most com mon
d escribed so the absence of cu taneou s vasod ilatory signs reaction associated w ith latex is an irritant contact dermatitis
and / or brad ycard ia instead of tachycard ia shou ld not p re- that is probably d ue to the alkaline pH of latex gloves.
clu d e the d iagnosis of anap hylaxis. H ealthcare w orkers, p atients w ith a history of m u ltip le
Table 1 2 .1 3 M ed ica t ion s a n d a ller gic r ea ct ion s

Local anesthetics • Anaphylactic reactions to amide local anesthetics are extremely rare
• True allergic reactions to esters account for 1% of reactions to local anesthetics
• Allergic reactions are usually due to paraaminobenzoic acid metabolite of esters or
methylparaben preservative
Muscle relaxants • Muscle relaxants account for most anaphylactic reactions during anesthesia
• Incidence: succinylcholine benzylisoquinoliniums aminosteroids
• Rocuronium: possible increased incidence when compared to other muscle relaxants
• Benzylisoquinolinium compounds can cause direct mast cell degranulation
Opioids • Allergic reactions to opioids are rare
• Morphine causes nonimmunologic histamine release
Propofol • Current evidence suggest that egg-allergic patients are not more likely to develop anaphylaxis
Inhaled anesthetics • Immune mediated hepatic injury
Aprotinin (serine protease inhibitor used to decrease • Antigenic, derived from bovine lung
blood loss and transfusion during certain cardiac • 2.5%–2.8% incidence of anaphylaxis on re-exposure
surgical procedures)
Heparin (232) • Antigenic, derived from bovine or porcine intestine
• Heparin induced thrombocytopenia is the most common nonanaphylactic reaction
Protamine (233,234) • Antigenic, derived from salmon sperm
• Slightly increased risk on reexposure and in diabetic patients exposed to neutral protamine
hagedorn or protamine zinc insulin
• Increased risk in vasectomized patients and those with fish allergies is controversial
Vancomycin • “Red man” syndrome of hypotension, pruritus, flushing and rash in 5%–14%; due to
nonimmunologic histamine release
• very rare cases of (Ig)-E mediated hypersensitivity reactions
Penicillins, cephalosporins
Isosulfan blue dye • Approved for intra-operative lymphatic mapping and sentinel node biopsy procedures for
breast cancer and melanoma
• 1%–2% incidence of allergic reactions including severe, anaphylactic reactions
su rgical proced u res, spina bifid a, atopic ind ivid u als, and of epinephrine and restoration/ expansion of circulating
those w ith fru it or food allergy (kiw i, chestnut, avocad o, intravascular volume. Poor outcomes following anaphylaxis
passion fru it, banana) are at increased risk of having a latex are associated w ith late or absent administration of epineph-
allergy. Parenteral or m ucus m em brane exposu re is most rine. Bronchospasm should be treated with inhaled and/ or
likely to lead to a severe reaction but a reaction can d evelop IV 2 agonist. Corticosteroid s and / or H1 receptor antago-
in response to inhalation of airborne latex particles. nists are often recommended in the management of anaphy-
Avoid ance of latex containing p rod u cts is the only effec- laxis, but their effects have never been established in
tive m anagem ent option in m ost cases (218). Latex allergic placebo-controlled trials. Likewise, the role of arginine vaso-
p atients shou ld be sched uled early in the d ay in ord er to pressin and methylene blue remains controversial.
red uce their exp osure to aeroallergens. Prophylactic ad m in-
istration of steroid s and antihistam ines is not effective and
is not recom m end ed . Certain d esensitization techniqu es
■ Positioning and peripheral nerve injury
m ay be effective in som e cases. A com p lete, thorou gh d iscu ssion of p atient p ositioning is
When intra-operative anaphylaxis is suspected, the fol- ou tsid e the scop e of this chap ter and the read er is referred
lowing initial treatment measures should be applied w hen- to textbooks and chap ters d ed icated to this su bject. In m ost
ever possible: (a) w ithdraw the suspected offend ing drug; textbooks and chapters covering positioning d uring sur-
(b) w hen the anaphylactic event occurs during induction, gery, a m ajor p ortion of the d iscu ssion is d evoted to m eth-
immed iately discontinue anesthetic drugs; (c) maintain the od s aim ed at red u cing p ostop erative com p lications of
airway with 100% oxygen; (d) in severe reactions, provid e p ositioning. As p ointed ou t in the ASA’s p ractice ad visory
early ad m inistration of epinephrine and call for help ; on p revention of p eriop erative p erip heral neuropathies,
(e) place the patient supine in the Trendelenburg position; there is scant evid ence of a cau sal relation betw een intra-
and (f) abbreviate the surgical proced ure if possible w hen it op erative p ositioning and p ostop erative neu ropathy (219).
occurs during surgery. A first priority is restoration of cardio- Perip heral nerve inju ry can be cau sed by m etabolic
vascular homeostasis primarily through early administration d erangem ent, ischem ia, excessive stretch, com pression or
p ressu re, d irect trau m a, or other u nknow n factors (220). The broad category of ocu lar inju ry is com p rised of variou s
Im prop er positioning of the patient is presu m ed to cau se typ es of inju ries inclu d ing corneal abrasion, vitreou s loss
p erip heral nerve injury through one or m ore of these m ech- and hem orrhage, and d am age to the retina or visu al path-
anism s. Other cau sative factors have been associated w ith w ay. The overall incid ence of ocu lar inju ry ap p ears to be
nerve inju ry inclu d ing au tom ated blood p ressu re cu ffs, low (0.06% to 0.17%) bu t m ay be greater in selected grou ps
subclinical d iabetes, ind u ced or p rolonged hypotension, su ch as p atients u nd ergoing op erations w ith card iop u l-
and stretch or com p ression d u ring operative m anipu lation. monary byp ass (223,224). In a closed claim s analysis of eye
N erves w ith a p reexisting inju ry are m u ch m ore su scep ti- inju ry associated w ith anesthesia, the m ost frequ ent com -
ble to p ermanent injury from a second , possibly su bclini- p lication resu lting in a claim w as corneal abrasion (225).
cal, insu lt in the op erating room . Patients m ay com e to the The other su bset of inju ry id entified in the closed claim s
operating room w ith a preexisting nerve inju ry from analysis w as characterized by p atient m ovem ent d uring
trau m a or com p ressive synd rom es, su ch as carpal tu nnel op hthalm ologic su rgery resu lting in blind ness.
synd rom e or thoracic outlet synd rom e.
Ulnar neu ropathy rep resents one third of all nerve Corneal Abrasions
injuries rep orted in the Closed Claims Project. The u lnar Risk factors for corneal abrasion inclu d e long su rgical p ro-
nerve ap p ears to be esp ecially vu lnerable to inju ry at the ced u res, lateral p ositioning, op eration on the head or neck,
elbow as it cou rses near the m ed ial ep icond yle of the and GA (224). In m ost cases of corneal abrasion, the exact
hu m eru s (221). The nerve can be constricted by the cu bital m echanism of inju ry is u nknow n. Postu lated m echanism s
tu nnel retinacu lum especially d u ring flexion of the elbow. inclu d e p rolonged exp osu re or contact w ith foreign bod ies.
Yet, it is d isconcerting that several stud ies su ggest that GA red u ces tear prod uction pred isposing the eye to d esic-
p erioperative m easu res to protect the u lnar nerve from cation and GA imp airs or obliterates p rotective behaviors
injury d o not p revent postop erative ulnar neu ropathy, and and reflexes. Corneal abrasions can occu r d esp ite taping
the cau se of u lnar neu ropathy m ay be beyond the control the eyelid s closed and / or ap p lying ointm ents. Injury p rior
of the anesthesiologist. In fact, m ost cases of ulnar neu rop a- to the p lacem ent of tap es has been d escribed . After ind u c-
thy m ay not be related to positioning at all. In a large retro- tion and p rior to the p lacem ent of eye tap es, the p atient is
spective stu d y of u lnar nerve inju ries follow ing d iagnostic at risk of inju ry from a variety of foreign bod ies includ ing
and noncard iac su rgical proced ures, p ersistent u lnar neu - w ristw atch band s, nam e bad ges, stethoscop es, IV tu bing,
ropathies w ere id entified in 414 cases, for an incid ence of 1 and m onitoring cables. Exp osu re keratitis can still occur if
p er 2,729 p atients (222). Seventy percent of the 414 p atients the eyelid s are not w ell ap p roxim ated after tap ing. Like-
w ith u lnar neu rop athy w ere m ale, 9% had bilateral neu - w ise, inclu sion of eyelashes u nd er the eyelid s d u ring tap-
ropathies, and m any occu rred even w hen precautions and ing, or contact of the ad hesive tap e w ith the cornea, can
p ad d ing w ere d ocu m ented . Univariate analysis revealed lead to inju ry. Once the tap es are rem oved , the p atient is at
the follow ing risk factors: m ale gend er, extrem es of w eight risk once again of corneal abrasion. Du ring em ergence,
(BMI 37 or less than 24), and a hospital stay greater than p atients have been observed to injure their ow n eyes by
14 d ays. N o association w as fou nd w ith the d u ration of reaching up to rub their face w ith an ind ex finger that has a
surgery, typ e of anesthetic, or p atient position d uring su r- p u lse oxim eter on it. The anesthetist can also cause injury
gery. Most cases p resented greater than 24 hou rs after the to the cornea at this tim e by d ragging objects across the
com pletion of the op eration. Interesting stu d ies in norm al p atient’s face.
consciou s m ale volu nteers reveal that p atients m ay not p er-
ceive p aresthesias of u lnar nerve com p ression even w hen Damage to the Retina or Visual Pathway
som atosensory evoked potentials d ocu m ent im paired elec- The retina can be d am aged throu gh occlu sion of the central
trophysiologic fu nction (221). Finally, u lnar neurop athy retinal artery or its branches. Central retinal artery occlu-
occurs in equ al frequ ency in m ed ical and su rgical p atients sion (CRAO) is thou ght to be d u e to d irect pressure on the
w ho are hosp italized for m ore than tw o d ays. Thu s, globe, emboli, or low p erfu sion p ressu re. Visu al loss is usu-
p atients, esp ecially sed ated and narcotized eld erly m en, ally u nilateral and p erm anent. Ischem ic op tic neu ropathy
w ho are in the sup ine position for a prolonged period of (ION ) resu lts from d am age to, or imp airm ent of, the circu-
time m ay be vu lnerable to u lnar neu ropathy w hether or latory su p p ly to the op tic nerve. The etiology of ION is
not they have had on op eration. u nknow n bu t it has been associated w ith large blood loss,
A variety of other com p lications of p ositioning are hyp otension, anem ia, the p rone p osition, and p reexisting
listed in Table 12.14. card iovascu lar d isease. Visu al im p airm ent is bilateral and
m ay imp rove w ith tim e in som e cases (226).
The incid ence of visu al loss d u e to CRAO and ION is
■ Ocular injury low and m ost inform ation is d erived from analysis of case
Inju ry to the eye is a potentially d isastrous com plication. rep orts and closed claim s (223,225). In Ju ly 1999, the Post-
Ocular inju ry m ay occu r d uring either ophthalm ologic sur- op erative Visu al Loss (POVL) Registry w as established to
gery or nonop hthalm ic su rgery and can range from rela- collect and analyze inform ation on closed claim s cases of
tively m inor corneal abrasion to perm anent loss of vision. visu al loss (227). The m ajority of cases in this analysis have
Table 1 2 .1 4 Com p lica t ion s of va r iou s p a t ien t p osit ion s d u r in g op era t ion s a n d d ia gn ost ic p roced u r es
Position Complications Possible Mechanism Potentially Protective Measures
Supine, head-down tilt Decreased pulmonary compliance, increased
work of breathing, increased inspiratory
pressures, increased intracranial pressure,
increased intracranial vascular congestion
Compression of subclavian neurovascular Shoulder brace malpositioned Place shoulder brace over the
bundle or neurovascular structures emerging acromioclavicular joint
from the area of the scalene musculature
Dorsal decubitus Postural hypotension with head-elevated Volume loading, vasopressors
posture
Pressure alopecia Turn head frequently and/or use padded
head support
Pressure point reaction (heels, elbows, Prolonged pressure while Proper padding
sacrum) immobile
Brachial plexus injuries Shoulder brace Place shoulder brace over the
acromioclavicular joint
Lateral displacement of head Secure head in neutral position
Sternal retraction
Long thoracic nerve dysfunction (etiology and prevention unclear)
Axillary trauma of the humeral head Avoid excess abduction of the arm
Radial nerve compression Pressure from vertical bar of Avoid prolonged pressure
anesthesia screen, sternal
retraction, excessive cycling of
blood pressure cuff
Avoid excessive cycling of automated
blood pressure cuff
Ulnar nerve at the elbow See text Use a padded armboard
Arm abduction should be limited to 90 in
supine patients
Position arm to decrease pressure on the
postcondylar groove of the humerus
Padded armboards and/or padding at the
elbow may decrease the risk of upper
extremity neuropathy
Backache Ligamentous relaxation during Maintain lumbar lordosis
general and regional anesthesia Place support under knees
Lateral decubitus Ocular injury (corneal abrasion, displacement Direct contact Protect (tape) eyes before turning
of lens, retinal ischemia)
Pressure on eye Avoid direct pressure to eyes
Systemic hypotension
Ear injury Dependent ear folded or Palpate ear to check padding
compressed
Neck pain Excessive lateral flexion, Secure head in neutral position
ventral flexion, extension
or rotation
Suprascapular injury Ventral circumduction of the Supporting pad under the thorax just
dependent shoulder caudad to the axilla
Long thoracic syndrome
Compartment syndrome of down-side Mediad compression or Supporting pad under the thorax just
upper extremity circumduction of down-side caudad to the axilla
shoulder
Aseptic necrosis of the upside femoral head Pressure compression of arterial Place restraining tapes across up-side on
blood supply the soft tissue between head of femur and
iliac crest
(continued)
Table 1 2 .1 4 Com p lica t ion s of va r iou s p a t ien t p osit ion s d u r in g op era t ion s a n d d ia gn ost ic
p r oced u r es (continued)
Position Complications Possible Mechanism Potentially Protective Measures
Ventral decubitus Ocular injury (corneal abrasion, displacement Direct contact Protect (tape) eyes before turning
(prone) of lens, retinal ischemia)
Pressure on eye Avoid direct pressure to eyes
Systemic hypotension
Neck pain Lateral rotation of head Keep head secured in sagittal plane
Ulnar and radial nerve injuries See text See supine position
Thoracic outlet syndrome (severe pain) Compression of brachial plexus Avoid overhead arm position in patients
and subclavian vessels near first with preoperative signs and symptoms of
rib thoracic outlet syndrome
Head-elevated Postural hypotension Volume loading, vasopressors, decrease
inhaled anesthetics, change patient position
incrementally
Air embolism Incised vein above the level of the
heart
Pneumocephalus Air trapped in superior regions of
cranium
Midcervical tetraplegia Marked flexion of neck with
stretching of spinal cord
compromising its vasculature in
midcervical area
Edema of face, tongue (macroglossia) Venous and lymphatic obstruction
and neck by prolonged neck flexion
op hthalmologic d iagnoses of ION and CROA and are asso- accou nted for a third of claim s and that 85% of these claim s
ciated w ith sp ine surgery (67%) follow ed by card iop u l- involved brain d am age or d eath (229). Most of these
monary byp ass p roced u res (10%). Interestingly, the POVL ad verse events w ere d u e to inad equ ate ventilation,
analysis has revealed strong evid ence that ION occu rs in esop hageal intu bation, and d ifficu lt tracheal intu bation.
the absence of d irect pressu re on the globe, in contrast to a Fu rtherm ore, m ost of these claim s w ere thou ght to be pre-
com m only held perception. ventable by p u lse oxim etry and cap nograp hy m onitoring.
Based p artly on these find ings, the ASA form u lated new
stand ard s for p eriop erative m onitoring that stress the u se
■ CONCLUSION
of p u lse oxim etry and cap nograp hy, and the ASA created
Most anesthesiologists w ou ld like to believe that the d eliv- p ractice gu id elines for m anagem ent of the d ifficu lt airw ay.
ery of anesthesia is relatively safe and that recent ad vances While the Closed Claim s Project cannot d eterm ine w hether
in m onitoring, p harm acology, anesthesia d elivery system s, the actu al incid ence of severe inju ries is d ecreasing, there
resid ent training, and inform ation technology have m ad e are trend s in ou tcom es that su ggest that this is so (228).
our p ractice even safer. Desp ite significant biases and lim i- The ad m inistration of anesthesia invokes rem arkable
tations, the Closed Claim s Project has provid ed inform a- p hysiologic changes that are som etim es su btle bu t often
tion su ggests that anesthesia care is becom ing safer. Stu d ies p rofou nd . The neu rological system is greatly affected ,
based on the Closed Claim s Project have influ enced anes- either regionally or globally. The state of anesthesia and the
thetic p ractice and stim u lated research in p roblem areas effects of the m ed ications used to block the response to
(228). For exam p le, the Closed Claim s Project has id entified noxiou s stim uli likew ise im pact the card iovascular and res-
that three d am aging events accou nt for nearly half of all p iratory system s. Anesthesia converts a relatively hard y,
claim s of inju ry: resp iratory system events, card iovascu lar ind ep end ent, and resilient p erson into a p atient w ho is
system events, and problems w ith equipm ent. The three d ep end ent, vu lnerable, and barely a few m om ents aw ay
most com m on com p lications or inju ries are d eath (30%), from jeop ard y, d am age, or d em ise. Mod ern anesthetic
brain d am age (12%) and nerve d am age (18%). Thu s, m an- p ractice has m ad e the p rocess seem rou tine, bu t w ith each
agem ent strategies d irected at these few areas of clinical anesthetic, there is a risk of com p lications or ad verse out-
practice m ay have large results on d ecreasing inju ry lead - com e. Unfortu nately, every su rgeon w ill becom e fam iliar
ing to claim s. Cheney et al. found that respiratory events w ith som e of the m ore com mon ad verse events and m ay
have a bru sh w ith som e of the rare ones as w ell. H op efu lly, 23. Bord et F, Allaou chiche B, Lansiau x S, et al. Risk factors for airw ay
com plications d u ring general anaesthesia in p aed iatric p atients. Pae-
the increasing com plexity of su rgical op erations, p resence diatr Anaesth 2002;12(9):762–769.
of m u ltip le com orbid cond itions, and ad vancing age of the 24. Seet E, You saf F, Gu p ta S, et al. Use of m anom etry for laryngeal m ask
patient p op u lation w ill not negate the positive im p act of airw ay red uces p ostoperative pharyngolaryngeal ad verse events: a
prospective, rand om ized trial. Anesthesiology 2010;112(3):652–657.
im provem ents in anesthesia safety. DOI:10.1097/ ALN .0b013e3181cf4346.
25. Geelhoed GW. Tracheom alacia from com p ressing goiter: m anage-
■ REFERENCES m ent after thyroid ectom y. Surgery 1988;104(6):1100–1108.
26. Rex MA. A review of the stru ctu ral and fu nctional basis of laryn-
1. Posner K. ASA Closed Claims Project. 2004. Available at: http :/ / d epts. gosp asm and a d iscu ssion of the nerve p athw ays involved in the
w ashington.ed u / asaccp . Accessed Janu ary 20, 2010. reflex and its clinical significance in m an and anim als. Br J Anaesth
2. Cap lan RA, Posner KL, Ward RJ, et al. Ad verse resp iratory events in 1970;42(10):891–899.
anesthesia: a closed claim s analysis. Anesthesiology 1990;72(5):828–833. 27. H artley M, Vau ghan RS. Problem s associated w ith tracheal extu ba-
3. Behringer EC. Ap p roaches to m anaging the u p p er airw ay. Anesthesiol tion [com m ent]. Br J Anaesth 1993;71(4):561–568.
Clin North America 2002;20(4):813–832, vi. 28. Lang SA, Du ncan PG, Shep hard DA, et al. Pu lm onary oed em a associ-
4. Rose DK, Cohen MM. The airw ay: p roblem s and p red ictions in 18,500 ated w ith airw ay obstru ction [com m ent]. Can J Anaesth 1990;37(2):
p atients [com m ent]. Can J Anaesth 1994;41(5, Pt 1):372–383. 210–218.
5. Chraem m er-Jorgensen B, H ertel S, Strom J, et al. Catecholam ine 29. Deep ika K, Kenaan CA, Barrocas AM, et al. N egative p ressu re p u l-
resp onse to laryngoscop y and intu bation. The influ ence of three d if- m onary ed em a after acu te u p p er airw ay obstru ction. J Clin Anesth
ferent d ru g com binations com m only u sed for ind u ction of anaesthe- 1997;9(5):403–408.
sia [com m ent]. Anaesthesia 1992;47(9):750–756. 30. H u g CC Jr. N ew p ersp ectives on anesthetic agents [Review ]. Am J
6. Barak M, Ziser A, Greenberg A, et al. H em od ynam ic and cate- Surg 1988;156(5):406–415.
cholam ine response to tracheal intubation: d irect laryngoscopy com - 31. Cam p agna JA, Miller KW, Form an SA. Mechanism s of actions of
pared w ith fiberop tic intu bation. J Clin Anesth 2003;15(2):132–136. inhaled anesthetics. N Engl J Med 2003;348(21):2110–2124.
7. Society of Anesthesiologists Task Force on Managem ent of the Diffi- 32. Bu ffington CW, Rom son JL, Levine A, et al. Isoflu rane ind u ces coro-
cu lt Airw ay. Practice gu id elines for m anagem ent of the d ifficult air- nary steal in a canine m od el of chronic coronary occlu sion. Anesthesi-
w ay. A report by the Am erican Society of Anesthesiologists Task Force ology 1987;66(3):280–292.
on Managem ent of the Difficu lt Airw ay. Anesthesiology 1993;78(3): 33. Tu m an KJ, McCarthy RJ, Sp iess BD, et al. Does choice of anesthetic
597–602. agent significantly affect ou tcom e after coronary artery su rgery?
8. Society of Anesthesiologists Task Force on Managem ent of the Diffi- Anesthesiology 1989;70(2):189–198.
cu lt Airw ay. Practice gu id elines for m anagem ent of the d ifficult air- 34. Cason BA, Verrier ED, Lond on MJ, et al. Effects of isoflu rane and
w ay: an upd ated rep ort by the Am erican Society of Anesthesiologists halothane on coronary vascular resistance and collateral m yocard ial
Task Force on Managem ent of the Difficu lt Airw ay. Anesthesiology blood flow : their cap acity to ind u ce coronary steal. Anesthesiology
2003;98(5):1269–1277. 1987;67(5):665–675.
9. Stern Y, Spitzer T. Retrograd e intu bation of the trachea. J Laryngol Otol 35. Pu lley DD, Kirvassilis GV, Kelerm enos N , et al. Regional and global
1991;105(9):746–747. m yocard ial circulatory and m etabolic effects of isoflu rane and
10. Mallam pati SR, Gatt SP, Gu gino LD, et al. A clinical sign to p red ict d if- halothane in p atients w ith steal-p rone coronary anatom y. Anesthesiol-
ficu lt tracheal intu bation: a p rosp ective stu d y. Can Anaesth Soc J 1985; ogy 1991;75(5):756–766.
32(4):429–434. 36. Agnew N M, Pennefather SH , Ru ssell GN . Isoflu rane and coronary
11. Frerk CM. Pred icting d ifficu lt intu bation [com m ent]. Anaesthesia 1991; heart d isease [com m ent]. Anaesthesia 2002;57(4):338–347.
46(12):1005–1008. 37. Tanaka K, Lu d w ig LM, Kersten JR, et al. Mechanism s of card iop rotec-
12. H agberg C, Boin MH . Managem ent of the airw ay: com p lications. In: tion by volatile anesthetics. Anesthesiology 2004;100(3):707–721.
Benu m of JL, Said m an LJ, ed s. Anesthesia and perioperative complica- 38. Aach R. H alothane and liver failu re. JAMA 1970;211(13):2145–2147.
tions, 2nd ed . St. Lou is: Mosby; 1999:3–24. 39. Elliott RH , Stru nin L. H ep atotoxicity of volatile anaesthetics. Br J
13. Rosenblatt W, Wagner P, Ovassap ian A, et al. Practice p atterns in m an- Anaesth 1993;70(3):339–348.
aging the d ifficu lt airw ay by anesthesiologists in the United States. 40. H ubbard AK, Roth TP, Gand olfi AJ, et al. H alothane hep atitis p atients
Anesth Analg 1998;87(1):153–157. generate an antibod y resp onse tow ard a covalently bou nd m etabolite
14. Warner ME, Benenfeld SM, Warner MA, et al. Perianesthetic d ental of halothane. Anesthesiology 1988;68(5):791–796.
injuries: frequ ency, ou tcom es, and risk factors. Anesthesiology 1999; 41. Kenna JG, Jones RM. The organ toxicity of inhaled anesthetics. Anesth
90(5):1302–1305. Analg 1995;81(6, Su pp l):S51–S66.
15. Loh KS, Irish JC. Trau m atic com p lications of intu bation and other air- 42. Conzen PF, Kharasch ED, Czerner SF, et al. Low -flow sevoflu rane
w ay m anagem ent p roced u res. In: Bogetz MS, ed . The upper airway and com p ared w ith low -flow isoflu rane anesthesia in p atients w ith stable
anesthesia. Philad elp hia, PA: W.B. Sau nd ers; 2002:953–969. renal insu fficiency [com m ent]. Anesthesiology 2002;97(3):578–584.
16. Lennarson PJ, Sm ith D, Tod d MM, et al. Segm ental cervical sp ine 43. Kharasch ED, Frink EJ Jr, Artru A, et al. Long-d u ration low -flow
m otion d uring orotracheal intu bation of the intact and inju red spine sevoflu rane and isoflu rane effects on postoperative renal and hepatic
w ith and w ithout external stabilization. J Neurosurg 2000;92(2, Su p p l): function. Anesth Analg 2001;93(6):1511–1520, table of contents.
201–206. 44. Forbes GM, Collins BJ. N itrou s oxid e for colonoscop y: a rand om ized
17. Du tton RP. Anesthetic m anagem ent of sp inal cord inju ry: clinical controlled stu d y [com m ent]. Gastrointest Endosc 2000;51(3):271–277.
p ractice and fu tu re initiatives. Int Anesthesiol Clin 2002;40(3):103– 45. H ard ing TA, Gibson JA. The u se of inhaled nitrou s oxid e for flexible
120. sigm oid oscop y: a p lacebo-controlled trial. Endoscopy 2000;32(6):
18. Weber S. Trau m atic com p lications of airw ay m anagem ent. In: Weber 457–460.
S, ed . Anesthesia-related complications. Philad elp hia, PA: W.B. Sau nd ers; 46. Eisele JH , Reitan JA, Massu m i RA, et al. Myocard ial p erform ance and
2002:265–274, v–vi. N 2O analgesia in coronary-artery d isease. Anesthesiology 1976;44(1):
19. H all CE, Shu tt LE. N asotracheal intu bation for head and neck su rgery 16–20.
[com m ent]. Anaesthesia 2003;58(3):249–256. 47. Flipp o TS, H old er WD Jr. N eu rologic d egeneration associated w ith
20. Conrard y PA, Good m an LR, Lainge F, et al. Alteration of end otracheal nitrou s oxid e anesthesia in p atients w ith vitam in B12 d eficiency. Arch
tu be position. Flexion and extension of the neck. Crit Care Med 1976; Surg 1993;128(12):1391–1395.
4(1):7–12. 48. Lou is-Ferd inand RT. Myelotoxic, neu rotoxic and rep rod u ctive
21. Parm et J, Colonna-Rom ano P, H orrow J, et al. The laryngeal m ask air- ad verse effects of nitrou s oxid e. Adverse Drug React Toxicol Rev 1994;
w ay reliably provid es rescu e ventilation in cases of unanticipated d if- 13(4):193–206.
ficu lt tracheal intu bation along w ith d ifficu lt m ask ventilation. Anesth 49. Suru d a A. H ealth effects of anesthetic gases. Occup Med 1997;12(4):
Analg 1998;87(3):661–665. 627–634.
22. Benum of JL. Laryngeal m ask airw ay and the ASA d ifficult airw ay 50. Eger EI II, Said m an LJ. H azard s of nitrou s oxid e anesthesia in bow el
algorithm [com m ent]. Anesthesiology 1996;84(3):686–699. obstru ction and p neu m othorax. Anesthesiology 1965;26(1):61–66.
51. Ohryn M. Tym p anic m em brane ru p tu re follow ing general anesthesia 80. Vasile B, Rasu lo F, Cand iani A, et al. The p athop hysiology of p rop ofol
w ith nitrou s oxid e: a case rep ort. AANA J 1995;63(1):42–44. infu sion synd rom e: a sim p le nam e for a com p lex synd rom e. Intensive
52. Seaberg RR, Freem an WR, Gold bau m MH , et al. Perm anent p ostop er- Care Med 2003;29(9):1417–1425.
ative vision loss associated w ith exp ansion of intraocu lar gas in the 81. Good ing JM, Dim ick AR, Tavakoli M, et al. A p hysiologic analysis of
p resence of a nitrou s oxid e-containing anesthetic. Anesthesiology 2002; card iopulm onary responses to ketam ine anesthesia in noncard iac
97(5):1309–1310. p atients. Anesth Analg 1977;56(6):813–816.
53. Astrom S, Kjellgren D, Monestam E, et al. N itrou s oxid e anesthesia 82. White PF, Way WL, Trevor AJ. Ketam ine–its p harm acology and thera-
and intravitreal gastam p onad e. Acta Anaesthesiol Scand 2003;47(3): p eu tic u ses. Anesthesiology 1982;56(2):119–136.
361–362. 83. Schow AJ, Lu barsky DA, Olson RP, et al. Can su ccinylcholine be u sed
54. Taylor E, Feinstein R, White PF, et al. Anesthesia for lap aroscop ic safely in hyp erkalem ic p atients? Anesth Analg 2002;95(1):119–122.
cholecystectomy. Is nitrous oxid e contraind icated? Anesthesiology 1992; 84. Thap a S, Brull SJ. Succinylcholine-ind u ced hyp erkalem ia in p atients
76(4):541–543. w ith renal failure: an old qu estion revisited . Anesth Analg 2000;91(1):
55. Cap lan RA, Vistica MF, Posner KL, et al. Ad verse anesthetic ou tcom es 237–241.
arising from gas d elivery equ ip m ent: a closed claim s analysis [com - 85. Wong SF, Chung F. Su ccinylcholine-associated p ostop erative m yalgia
m ent]. Anesthesiology 1997;87(4):741–748. [com m ent]. Anaesthesia 2000;55(2):144–152.
56. Anagnostou JM, Stoelting RK. Com p lications of d ru gs u sed in anes- 86. Pace N L. The best p rop hylaxis for su ccinylcholine m yalgias: exten-
thesia. In: Benu m of JL, Said m an LJ, ed s. Anesthesia and perioperative sion of a p reviou s m eta-analysis. Anesth Analg 1993;77(5):1080–1081.
complications. St. Lou is: Mosby; 1999:161–191. 87. Cu nningham AJ, Barry P. Intraocu lar p ressu re–p hysiology and im p li-
57. H irshm an CA, Ed elstein RA, Ebertz JM, et al. Thiobarbitu rate- cations for anaesthetic m anagem ent. Can Anaesth Soc J 1986;33(2):
ind uced histam ine release in hu m an skin m ast cells. Anesthesiology 195–208.
1985;63(4):353–356. 88. Mitra S, Gom bar KK, Gom bar S. The effect of rocu roniu m on intraoc-
58. H arrison GG, Meissner PN , H ift RJ. Anaesthesia for the p orp hyric u lar p ressu re: a com p arison w ith su ccinylcholine. Eur J Anaesthesiol
p atient [com m ent]. Anaesthesia 1993;48(5):417–421. 2001;18(12):836–838.
59. Ben-Shlom o I, abd -el-Khalim H , Ezry J, et al. Mid azolam acts syner- 89. Zim m erm an AA, Fu nk KJ, Tid w ell JL. Prop ofol and alfentanil p revent
gistically w ith fentanyl for ind u ction of anaesthesia. Br J Anaesth 1990; the increase in intraocu lar p ressu re cau sed by su ccinylcholine and
64(1):45–47. end otracheal intu bation d u ring a rapid sequ ence ind u ction of anes-
60. H eikkila H , Jalonen J, Arola M, et al. Mid azolam as ad ju nct to high- thesia. Anesth Analg 1996;83(4):814–817.
d ose fentanyl anaesthesia for coronary artery byp ass grafting op era- 90. Moreno RJ, Kloess P, Carlson DW. Effect of su ccinylcholine on the
tion. Acta Anaesthesiol Scand 1984;28(6):683–689. intraocular contents of open globes [com m ent]. Ophthalmology 1991;
61. Vinik H R, Brad ley EL Jr, Kissin I. Mid azolam -alfentanil synergism for 98(5):636–638.
anesthetic ind u ction in p atients. Anesth Analg 1989;69(2):213–217. 91. McGold rick KE. The op en globe: is an alternative to su ccinylcholine
62. Zacharias M, Du nd ee JW, Clarke RS, et al. Effect of p reanaesthetic necessary? [com m ent]. J Clin Anesth 1993;5(1):1–4.
m ed ication on etom id ate. Br J Anaesth 1979;51(2):127–133. 92. Vachon CA, Warner DO, Bacon DR. Su ccinylcholine and the op en
63. Wagner RL, White PF, Kan PB, et al. Inhibition of ad renal steroid ogen- globe. Tracing the teaching. Anesthesiology 2003;99(1):220–223.
esis by the anesthetic etom id ate. N Engl J Med 1984;310(22):1415–1421. 93. Cook DR. Can su ccinylcholine be aband oned ? Anesth Analg 2000;
64. Wagner RL, White PF. Etom id ate inhibits ad renocortical fu nction in 90(Su p p l 5):S24–S28.
surgical p atients. Anesthesiology 1984;61(6):647–651. 94. Sp arr H J, Beau fort TM, Fu chs-Bu d er T. N ew er neu rom u scu lar block-
65. Crozier TA, Beck D, Schlaeger M, et al. End ocrinological changes fol- ing agents: how d o they com pare w ith established agents? Drugs
low ing etom id ate, m id azolam , or m ethohexital for m inor surgery. 2001;61(7):919–942.
Anesthesiology 1987;66(5):628–635. 95. Moore EW, H u nter JM. The new neu rom u scu lar blocking agents: d o
66. Good ing JM, Corssen G. Effect of etom id ate on the card iovascu lar they offer any ad vantages? Br J Anaesth 2001;87(6):912–925.
system . Anesth Analg 1977;56(5):717–719. 96. Cam m u G. Interactions of neu rom u scu lar blocking d ru gs. Acta Anaes-
67. Price ML, Millar B, Grou nd s M, et al. Changes in card iac ind ex and thesiol Belg 2001;52(4):357–363.
estim ated system ic vascular resistance d u ring ind uction of anaesthe- 97. Fod ale V, Santam aria LB. Lau d anosine, an atracu riu m and
sia w ith thiopentone, m ethohexitone, p rop ofol and etom id ate [com - cisatracu riu m m etabolite. Eur J Anaesthesiol 2002;19(7):466–473.
m ent]. Br J Anaesth 1992;69(2):172–176. 98. Mu rphy GS, Vend er JS. N eu rom u scu lar-blocking d ru gs. Use and
68. Good m an N W, Black AM, Carter JA. Som e ventilatory effects of m isuse in the intensive care u nit. Crit Care Clin 2001;17(4):925–
p ropofol as sole anaesthetic agent. Br J Anaesth 1987;59(12):1497–1503. 942.
69. Lepage JY, Pinau d ML, H elias JH , et al. Left ventricu lar p erform ance 99. Prielipp RC, Cou rsin DB, Wood KE, et al. Com p lications associated
d u ring p rop ofol or m ethohexital anesthesia: isotop ic and invasive w ith sed ative and neu rom uscu lar blocking d ru gs in critically ill
card iac m onitoring. Anesth Analg 1991;73(1):3–9. p atients. Crit Care Clin 1995;11(4):983–1003.
70. Claeys MA, Gepts E, Cam u F. H aem od ynam ic changes d u ring anaes- 100. Douglass JA, Tu xen DV, H orne M, et al. Myop athy in severe asthm a.
thesia ind u ced and m aintained w ith p rop ofol. Br J Anaesth 1988; Am Rev Respir Dis 1992;146(2):517–519.
60(1):3–9. 101. Segred o V, Cald w ell JE, Matthay MA, et al. Persistent p aralysis in crit-
71. Prys-Roberts C, Davies JR, Calverley RK, et al. H aem od ynam ic effects ically ill patients after long-term ad m inistration of vecu roniu m .
of infusions of d iisoprop yl p henol (ICI 35 868) d u ring nitrou s oxid e N Engl J Med 1992;327(8):524–528.
anaesthesia in m an. Br J Anaesth 1983;55(2):105–111. 102. Coursin DB, Prielip p RC. Prolonged p aralysis w ith atracu riu m infu -
72. Sosis MB, Braverm an B. Grow th of Stap hylococcu s au reu s in four sion. Crit Care Med 1995;23(6):1155–1157.
intravenous anesthetics. Anesth Analg 1993;77(4):766–768. 103. Prielipp RC, Cou rsin DB, Scu d eri PE, et al. Com p arison of the infu -
73. Bennett SN , McN eil MM, Bland LA, et al. Postop erative infections sion requ irem ents and recovery p rofiles of vecu roniu m and
traced to contam ination of an intravenou s anesthetic, p rop ofol [com - cisatracu riu m 51W89 in intensive care u nit p atients. Anesth Analg
m ent]. N Engl J Med 1995;333(3):147–154. 1995;81(1):3–12.
74. Veber B, Gachot B, Bed os JP, et al. Severe sep sis after intravenou s 104. Mu rray MJ, Cow en J, DeBlock H , et al. Clinical p ractice gu id elines for
injection of contam inated p rop ofol. Anesthesiology 1994;80(3):712– su stained neu rom u scu lar blockad e in the ad u lt critically ill p atient.
713. Crit Care Med 2002;30(1):142–156.
75. N ichols RL, Sm ith JW. Bacterial contam ination of an anesthetic agent 105. Flacke JW, Flacke WE, Bloor BC, et al. H istam ine release by fou r nar-
[com m ent]. N Engl J Med 1995;333(3):184–185. cotics: a d ouble-blind stu d y in hu m ans. Anesth Analg 1987;66(8):
76. Bach A, Geiss H K. Prop ofol and p ostop erative infections [com m ent]. 723–730.
N Engl J Med 1995;333(22):1505–1506; d iscu ssion 1507. 106. Sim op ou los TT, Sm ith H S, Peeters-Asd ou rian C, et al. Use of m ep eri-
77. Sklar GE. Prop ofol and p ostop erative infections. Ann Pharmacother d ine in p atient-controlled analgesia and the d evelop m ent of a
1997;31(12):1521–1523. norm eperid ine toxic reaction. Arch Surg 2002;137(1):84–88.
78. Gu teliu s B, Perz JF, Parker MM, et al. Mu ltip le clu sters of hep atitis 107. Michelsen LG, H u g CC Jr. The p harm acokinetics of rem ifentanil.
viru s infections associated w ith anesthesia for ou tp atient end oscop y J Clin Anesth 1996;8(8):679–682.
p roced ures. Gastroenterology 2010;139(1):163–170. 108. Patel P, Sun L. Up d ate on neonatal anesthetic neu rotoxicity: insight
79. Labu s B. Outbreak of hepatitis C at outpatient surgical centers. Las Vegas: into m olecular m echanism s and relevance to hu m ans [com m ent].
Southern N evad a H ealth District; 2009. Anesthesiology 2009;110(4):703–708.
109. Cottrell JE, Cottrell JE. We care, therefore w e are: anesthesia-related 136. Morishim a H O, Ped ersen H , Finster M, et al. Bu p ivacaine toxicity in
m orbid ity and m ortality: the 46th rovenstine lectu re. Anesthesiology p regnant and nonpregnant ew es. Anesthesiology 1985;63(2):134–139.
2008;109(3):377–388. 137. Mather LE, Copeland SE, Lad d LA. Acu te toxicity of local anesthetics:
110. Jevtovic-Tod orovic V, Olney JW. PRO: Anesthesia-ind u ced d evelop - u nd erlying pharm acokinetic and p harm acod ynam ic concep ts. Reg
m ental neuroap op tosis: statu s of the evid ence. Anesth Analg 2008; Anesth Pain Med 2005;30(6):553–566.
106(6):1659–1663. 138. Scott DB. “Maxim u m recom m end ed d oses” of local anaesthetic
111. Olney JW, Young C, Wozniak DF, et al. Anesthesia-ind u ced d evelop - d ru gs. Br J Anaesth 1989;63(4):373–374.
m ental neu roapop tosis: d oes it hap p en in hu m ans? [Ed itorial]. Anes- 139. Rosenberg PH , Veering BT, Urm ey WF. Maxim u m recom m end ed
thesiology 2004;101(2):273–275. d oses of local anesthetics: a m u ltifactorial concep t. Reg Anesth Pain
112. Jevtovic-Tod orovic V, H artm an RE, Izu m i Y, et al. Early exposu re to Med 2004;29(6):564–575.
com m on anesthetic agents cau ses w id esp read neurod egeneration in 140. Brow n D, Ransom D, H all J, et al. Regional anesthesia and local anes-
the d evelop ing rat brain and p ersistent learning d eficits. J Neurosci thetic-ind uced system ic toxicity: seizu re frequency and accom pany-
2003;23(3):876–882. ing card iovascular changes. Anesth Analg 1995;81(2):321–328.
113. Fred riksson A, Ponten E, Gord h T, et al. N eonatal exp osu re to a com - 141. Braid DP, Scott DB. Effect of ad renaline on the system ic absorp tion of
bination of N -m ethyl-D-asp artate and gam m a-am inobu tyric acid local anaesthetic d ru gs. Acta Anaesthesiol Scand Suppl 1966;23:334–346.
typ e A receptor anesthetic agents potentiates apoptotic neurod egen- 142. N eal JM, Bernard s CM, Bu tterw orth JFIV, et al. ASRA p ractice ad vi-
eration and persistent behavioral d eficits. Anesthesiology 2007;107(3): sory on local anesthetic system ic toxicity. Reg Anesth Pain Med 2010;
427–436. 35(2):152–161.
114. Yon J-H , Carter LB, Reiter RJ, et al. Melatonin red u ces the severity of 143. Weinberg GL, Rip per R, Feinstein DL, et al. Lip id em u lsion infu sion
anesthesia-ind u ced ap op totic neu rod egeneration in the d evelop ing rescues d ogs from bu pivacaine-ind u ced card iac toxicity [see com -
rat brain. Neurobiol Dis 2006;21(3):522–530. m ent]. Reg Anesth Pain Med 2003;28(3):198–202.
115. Kalkm an CJMDPD, Peelen LMS, Moons KGPD, et al. Behavior and 144. Perez-Castro R, Patel S, Garavito-Agu ilar ZV, et al. Cytotoxicity of
d evelop m ent in child ren and age at the tim e of first anesthetic exp o- local anesthetics in hu m an neu ronal cells. Anesth Analg 2009;108(3):
su re. Anesthesiology 2009;110(4):805–812. 997–1007.
116. Wild er RTMDPD, Flick RPMDMPH , Sp ru ng JMDPD, et al. Early 145. Zink W, Graf BM. Local anesthetic m yotoxicity. Reg Anesth Pain Med
exposu re to anesthesia and learning d isabilities in a population-based 2004;29(4):333–340.
birth cohort. Anesthesiology 2009;110(4):796–804. 146. Zink W, Seif C, Bohl JR, et al. The acu te m yotoxic effects of bu p iva-
117. Mellon RD, Sim one AF, Rap p ap ort BA. Use of anesthetic agents in caine and ropivacaine after continu ou s p eripheral nerve blockad es.
neonates and you ng child ren. Anesth Analg 2007;104(3):509–520. Anesth Analg 2003;97(4):1173–1179, table of contents.
118. Moller JT, Cluitm ans P, Rasm u ssen LS, et al. Long-term p ostoperative 147. Zink W, Bohl JRE, H acke N , et al. The long term m yotoxic effects of
cognitive d ysfunction in the eld erly: ISPOCD1 stu d y. Lancet 1998; bu p ivacaine and rop ivacaine after continu ou s p erip heral nerve
351(9106):857–861. blocks. Anesth Analg 2005;101(2):548–554.
119. Monk TG, Weld on BC, Garvan CW, et al. Pred ictors of cognitive d ys- 148. Gom ez-Arnau JI, Yangu ela J, Gonzalez A, et al. Anaesthesia-related
fu nction after m ajor noncard iac su rgery. Anesthesiology 2008;108(1): d ip lopia after cataract su rgery. Br J Anaesth 2003;90(2):189–193.
18–30. 149. Bu sfield BT, Rom ero DM. Pain p u m p u se after shou ld er arthroscop y
120. N ew m an MF, Kirchner JL, Phillip s-Bu te B, et al. Longitu d inal assess- as a cause of glenohu m eral chond rolysis. Arthroscopy 2009;25(6):
m ent of neurocognitive fu nction after coronary-artery bypass surgery. 647–652.
N Engl J Med 2001;344(6):395–402. 150. Liu SS, McDonald SB. Cu rrent issu es in sp inal anesthesia [com m ent].
121. Matthey P, Finucane BT, Finegan BA. The attitu d e of the general p ub- Anesthesiology 2001;94(5):888–906.
lic tow ard s preop erative assessm ent and risks associated w ith general 151. Lam bert DH , H u rley RJ, H ertw ig L, et al. Role of need le gau ge and tip
anesthesia. Can J Anaesth 2001;48(4):333–339. configu ration in the p rod u ction of lu m bar p u nctu re head ache. Reg
122. Kerssens C, Klein J, Bonke B. Aw areness: Monitoring versu s rem em - Anesth 1997;22(1):66–72.
bering w hat happ ened . Anesthesiology 2003;99(3):570–575. 152. Lybecker H , Moller JT, May O, et al. Incid ence and p red iction of p ost-
123. Sand in RH , Enlu nd G, Sam u elsson P, et al. Aw areness d u ring anaes- d u ral p u ncture head ache. A p rosp ective stu d y of 1021 sp inal anesthe-
thesia: a prosp ective case stu d y. Lancet 2000;355(9205):707–711. sias. Anesth Analg 1990;70(4):389–394.
124. Bailey AR, Jones JG. Patients’ m em ories of events d u ring general 153. Gerancher JC, Liu SS. Com p lications of neu raxial (sp inal/ ep id u ral/
anaesthesia. Anaesthesia 1997;52(5):460–476. cau d al) anesthesia. In: Benu m of JL, ed . Anesthesia and perioperative
125. Russell IF. Mid azolam -alfentanil: an anaesthetic? An investigation complications, 2nd ed . St. Lou is: Mosby; 1999:50–65.
u sing the isolated forearm techniqu e. Br J Anaesth 1993;70(1):42–46. 154. Vercau teren MP, H offm ann VH , Mertens E, et al. Seven-year review of
126. Tem pe DK, Sid d iqu ie RA. Aw areness d u ring card iac su rgery. J Cardio- requests for epid ural blood patches for head ache after d u ral punc-
thorac Vasc Anesth 1999;13(2):214–219. tu re: referral p atterns and the effectiveness of blood p atches. Eur J
127. Osterm an JE, H op p er J, H eran WJ, et al. Aw areness u nd er anesthesia Anaesthesiol 1999;16(5):298–303.
and the d evelop m ent of p osttrau m atic stress d isord er. Gen Hosp Psy- 155. Safa-Tisseront V, Thorm ann F, Malassine P, et al. Effectiveness of
chiatry 2001;23(4):198–204. epid u ral blood patch in the m anagem ent of p ost-d u ral p unctu re
128. Dom ino KB, Posner KL, Cap lan RA, et al. Aw areness d u ring anesthe- head ache [com m ent]. Anesthesiology 2001;95(2):334–339.
sia: a closed claim s analysis. Anesthesiology 1999;90(4):1053–1061. 156. Beard s SC, Jackson A, Griffiths AG, et al. Magnetic resonance im aging
129. Bergm an IJ, Klu ger MT, Short TG. Aw areness d u ring general anaes- of extrad u ral blood p atches: ap p earances from 30 m in to 18 h [com -
thesia: a review of 81 cases from the Anaesthetic Incid ent Monitoring m ent]. Br J Anaesth 1993;71(2):182–188.
Stud y. Anaesthesia 2002;57(6):549–556. 157. Gu p ta S, Tarkkila P, Finu cane BT. Com p lications of central neu ral
130. Ghoneim MM, Block RI, H affarnan M, et al. Aw areness d u ring anes- blockad e. In: Finucane BT, ed . Complications of regional anesthesia.
thesia: risk factors, cau ses and sequ elae: a review of rep orted cases in Philad elphia, PA: Chu rchill Livingstone; 1999:184–212.
the literatu re. Anesth Analg 2009;108(2):527–535. 158. Breen TW, Ransil BJ, Groves PA, et al. Factors associated w ith back
131. Ku rosaw a S, Kato M, Ku rosaw a S, et al. Anesthetics, im m u ne cells, p ain after child birth. Anesthesiology 1994;81(1):29–34.
and im m u ne resp onses. J Anesthesia 2008;22(3):263–277. 159. H irabayashi Y, Igarashi T, Su zu ki H , et al. Mechanical effects of leg
132. Mulroy MF. System ic toxicity and card iotoxicity from local anesthet- p osition on vertebral stru ctu res exam ined by m agnetic resonance
ics: incid ence and p reventive m easu res. Reg Anesth Pain Med 2002; im aging. Reg Anesth Pain Med 2002;27(4):429–432.
27(6):556–561. 160. Pertek JP, H aberer JP. [Effects of anesthesia on p ostop erative m ictu ri-
133. Liu PL, Feld m an H S, Giasi R, et al. Com parative CN S toxicity of lid o- tion and u rinary retention]. Ann Fr Anesth Reanim 1995;14(4):340–351.
caine, etid ocaine, bu p ivacaine, and tetracaine in aw ake d ogs follow ing 161. Petros JG, Rim m EB, Robillard RJ. Factors influ encing u rinary tract
rapid intravenous ad m inistration. Anesth Analg 1983;62(4):375–379. retention after elective op en cholecystectom y. Surg Gynecol Obstet
134. Covino BG. Toxicity of local anesthetic agents. Acta Anaesthesiol Belg 1992;174(6):497–500.
1988;39(3, Su pp l 2):159–164. 162. Jensen P, Mikkelsen T, Kehlet H . Postherniorrhap hy u rinary reten-
135. Clarkson CW, H ond eghem LM. Mechanism for bu p ivacaine d ep res- tion–effect of local, regional, and general anesthesia: A review. Reg
sion of card iac cond uction: fast block of sod ium channels d uring the Anesth Pain Med 2002;27(6):612–617.
action p otential w ith slow recovery from block d u ring d iastole. Anes- 163. Pollock JE. Transient neu rologic sym p tom s: etiology, risk factors, and
thesiology 1985;62(4):396–405. m anagem ent [com m ent]. Reg Anesth Pain Med 2002;27(6):581–586.
164. Pollock JE, Liu SS, N eal JM, et al. Dilu tion of sp inal lid ocaine d oes not 191. Ap fel CC, Laara E, Koivu ranta M, et al. A sim p lified risk score for p re-
alter the incid ence of transient neu rologic sym p tom s. Anesthesiology d icting p ostop erative nau sea and vom iting: conclu sions from cross-
1999;90(2):445–450. valid ations betw een tw o centers. Anesthesiology 1999;91(3):693–700.
165. Vand erm eu len EP, Van Aken H , Verm ylen J. Anticoagu lants and 192. Du rm u s M, Karaaslan E, Oztu rk E, et al. The effects of single-d ose
sp inal-epid u ral anesthesia [com m ent]. Anesth Analg 1994;79(6):1165– d exam ethasone on w ou nd healing in rats. Anesth Analg 2003;97(5):
1177. 1377–1380.
166. H orlocker TT. Low m olecu lar w eight hep arin and neu raxial anesthe- 193. Gan TJ, El-Molem H , Ray J, et al. Patient-controlled antiem esis: a ran-
sia. Thromb Res 2001;101(1):141–154. d om ized , d ou ble-blind com p arison of tw o d oses of p rop ofol versu s
167. Kind ler CH , Seeberger MD, Staend er SE. Ep id u ral abscess com plicat- p lacebo. Anesthesiology 1999;90(6):1564–1570.
ing ep id u ral anesthesia and analgesia. An analysis of the literatu re 194. Ad am s JP, Mu rp hy PG. Obesity in anaesthesia and intensive care. Br J
[com m ent]. Acta Anaesthesiol Scand 1998;42(6):614–620. Anaesth 2000;85(1):91–108.
168. Wang LP, H auerberg J, Schm id t JF. Incid ence of sp inal epid u ral 195. Bray GA. Risks of obesity. Prim Care 2003;30(2):281–99, v–vi.
abscess after epid u ral analgesia: a national 1-year su rvey. Anesthesiol- 196. Benu m of JL. Obstru ctive sleep ap nea in the ad u lt obese p atient: im p li-
ogy 1999;91(6):1928–1936. cations for airw ay m anagem ent. J Clin Anesth 2001;13(2):144–156.
169. Canto M, Casas A, Sanchez MJ, et al. Thoracic ep id u rals in heart valve 197. Esclam ad o RM, Glenn MG, McCu lloch TM, et al. Periop erative com -
su rgery: neu rologic risk evalu ation. J Cardiothorac Vasc Anesth 2002; p lications and risk factors in the su rgical treatm ent of obstru ctive
16(6):723–726. sleep ap nea synd rom e. Laryngoscope 1989;99(11):1125–1159.
170. Wysow ski DK, Talarico L, Bacsanyi J, et al. Sp inal and ep id u ral 198. Forrest JB, Rehd er K, Cahalan MK, et al. Mu lticenter stu d y of general
hem atom a and low -m olecu lar-w eight hep arin. N Engl J Med 1998; anesthesia. III. Pred ictors of severe p eriop erative ad verse ou tcom es
338(24):1774–1775. [com m ent]. Anesthesiology 1992;76(1):3–15; erratu m Anesthesiology
171. Lu m p kin MM. FDA p u blic health ad visory. Anesthesiology 1998; 1992;77(1):222.
88(2):27A–28A. 199. Pelosi P, Croci M, Ravagnan I, et al. The effects of bod y m ass on lu ng
172. H orlocker T, H eit J. Low m olecu lar w eight hep arin: biochem istry, volu m es, resp iratory m echanics, and gas exchange d u ring general
p harm acology, periop erative p rop hylaxis regim ens, and gu id elines anesthesia. Anesth Analg 1998;87(3):654–660.
for regional anesthetic m anagem ent. Anesth Analg 1997;85(4):874–885. 200. Duflou J, Virm ani R, Rabin I, et al. Su d d en d eath as a resu lt of heart
173. Bergqvist D, Wu CL, N eal JM. Anticoagu lation and neu raxial regional d isease in m orbid obesity. Am Heart J 1995;130(2):306–313.
anesthesia: p erspectives. Reg Anesth Pain Med 2003;28(3):163–166. 201. Choban PS, Flancbau m L. The im p act of obesity on su rgical ou tcom es:
174. H orlocker TT, Wed el DJ, Benzon H , et al. Regional anesthesia in the a review. J Am Coll Surg 1997;185(6):593–603.
anticoagu lated patient: d efining the risks (the second ASRA Consen- 202. Mou lton MJ, Cresw ell LL, Mackey ME, et al. Obesity is not a risk fac-
su s Conference on N eu raxial Anesthesia and Anticoagu lation). Reg tor for significant ad verse ou tcom es after card iac su rgery. Circulation
Anesth Pain Med 2003;28(3):172–197. 1996;94(Su p pl 6):II87–II92.
175. Au roy Y, N archi P, Messiah A, et al. Seriou s com p lications related to 203. Fasol R, Schind ler M, Schu m acher B, et al. The influ ence of obesity on
regional anesthesia: results of a prospective survey in France [com - periop erative m orbid ity: retrosp ective stu d y of 502 aortocoronary
m ent]. Anesthesiology 1997;87(3):479–486. bypass op erations. Thorac Cardiovasc Surg 1992;40(3):126–129.
176. Cheney FW, Dom ino KB, Cap lan RA, et al. N erve inju ry associated 204. Sessler DI. Com plications and treatm ent of m ild hyp otherm ia. Anes-
w ith anesthesia: a closed claim s analysis. Anesthesiology 1999;90(4): thesiology 2001;95(2):531–543.
1062–1069. 205. Sessler DI. Mild perioperative hyp otherm ia. N Engl J Med 1997;
177. Reynold s F. Dam age to the conu s m ed u llaris follow ing sp inal anaes- 336(24):1730–1737.
thesia [com m ent]. Anaesthesia 2001;56(3):238–247. 206. Ku rz A, Sessler DI, Lenhard t R, et al. Periop erative N orm otherm ia to
178. Ben-David B, Raw a R. Com p lications of neu raxial blockad e. In: Weber Red u ce the Incid ence of Su rgical-Wou nd Infection and Shorten
S, ed . Anesthesia-related complications. Philad elp hia, PA: W.B. Sau nd ers; H osp italization. N Engl J Med 1996;334(19):1209–1216.
2002:669–694. 207. Winkler M, Akca O, Birkenberg B, et al. Aggressive w arm ing red u ces
179. Lesser JB, Sanborn KV, Valskys R, et al. Severe brad ycard ia d uring blood loss d u ring hip arthrop lasty. Anesth Analg 2000;91(4):978–984.
spinal and epid u ral anesthesia record ed by an anesthesia inform ation 208. Cheney FW, Posner KL, Cap lan RA, et al. Bu rns from w arm ing
m anagem ent system . Anesthesiology 2003;99(4):859–866. d evices in anesthesia. A closed claim s analysis [com m ent]. Anesthesi-
180. Carp enter RL, Caplan RA, Brow n DL, et al. Incid ence and risk factors ology 1994;80(4):806–810.
for sid e effects of spinal anesthesia [com m ent]. Anesthesiology 1992; 209. Rosenberg H , Frank SM. Cau ses and consequ ences of hyp otherm ia
76(6):906–916. and hypertherm ia. In: Benu m of JL, Said m an LJ, ed s. Anesthesia and
181. Cu ratolo M, Scaram ozzino P, Venu ti F, et al. Factors associated w ith perioperative complications, 2nd ed . St. Lou is: Mosby; 1999:338–356.
hypotension and brad ycard ia after ep id u ral blockad e. Anesth Analg 210. MacLennan DH , Phillip s MS. Malignant hyp ertherm ia. Science
1996;83(5):1033–1040. 1992;256(5058):789–794.
182. Caplan RA, Ward RJ, Posner K, et al. Unexp ected card iac arrest d u r- 211. Fasting S, Gisvold SE. Seriou s intraop erative p roblem s—a five-year
ing spinal anesthesia: a closed claim s analysis of p red isp osing factors review of 83,844 anesthetics: [Problem es p erop eratoires graves—u ne
[com m ent]. Anesthesiology 1988;68(1):5–11. revue d e 83 844 anesthesies su r cinq ans]. Can J Anaesth 2002;49(6):
183. Au roy Y, Benham ou D, Bargu es L, et al. Major com p lications of 545–553.
regional anesthesia in France: The SOS Regional Anesthesia H otline 212. H ep ner DL, Castells MC. Anap hylaxis d u ring the p eriop erative
Service [com m ent]. Anesthesiology 2002;97(5):1274–1280. period . Anesth Analg 2003;97(5):1381–1395.
184. Pollard JB. Card iac arrest d u ring sp inal anesthesia: com m on m echa- 213. Dew achter P, Mou ton-Faivre C, Em ala CW. Anap hylaxis and anesthe-
nism s and strategies for p revention. Anesth Analg 2001;92(1):252–256. sia: controversies and new insights. Anesthesiology 2009;111(5):1141–
185. Rosenberg J, Wahr J, Su ng C, et al. Coronary p erfu sion p ressure d ur- 1150.
ing card iopulm onary resuscitation after spinal anesthesia in d ogs. 214. Kou nis N G. Kounis synd rom e (allergic angina and allergic m yocar-
Anesth Analg 1996;82(1):84–87. d ial infarction): a natu ral p arad igm ? Int J Cardiol 2006;110(1):7–14.
186. Rosenberg JM, Wortsm an J, Wahr JA, et al. Im p aired neu roend ocrine 215. Laxenaire MC, Mertes PM, Grou p e d ’Etu d es d es Reactions Anap hy-
response m ed iates refractoriness to card iopu lm onary resuscitation in lactoid es Peranesthesiques. Anap hylaxis d u ring anaesthesia. Resu lts
spinal anesthesia. Crit Care Med 1998;26(3):533–537. of a tw o-year survey in France. Br J Anaesth 2001;87(4):549–558.
187. Watcha MF. Postoperative nau sea and em esis. In: Weber S, ed . 216. Bald o BA, Fisher MM, Pham N H . On the origin and sp ecificity of anti-
Anesthesia-related complications. Philad elp hia, PA: W.B. Sau nd ers; 2002: bod ies to neu rom u scular blocking (m u scle relaxant) d ru gs: an
709–722. im m unochem ical p erspective. Clin Exp Allergy 2009;39(3):325–344.
188. Gan TJ, Meyer T, Ap fel CC, et al. Consensu s gu id elines for m anaging 217. Ford S, Kam P, Bald o B, et al. Anap hylactic or anap hylactoid reactions
p ostop erative nausea and vom iting. Anesth Analg 2003;97(1):62–71. in p atients u nd ergoing card iac su rgery. J Cardiothorac Vasc Anesth
189. Ap fel CC, Kranke P, Katz MH , et al. Volatile anaesthetics m ay be the 2001;15(6):684–688.
m ain cau se of early bu t not d elayed p ostoperative vom iting: a ran- 218. H ep ner DL, Castells MC. Latex allergy: an u p d ate. Anesth Analg
d om ized controlled trial of factorial d esign [com m ent]. Br J Anaesth 2003;96(4):1219–1229.
2002;88(5):659–668. 219. Am erican Society of Anesthesiologists Task Force on Prevention of
190. Sw eeney BP. Ed itorial II: Why d oes sm oking p rotect against PON V? Periop erative Peripheral N eu rop athies. Practice ad visory for the p re-
Br J Anaesth 2002;89(6):810–813. vention of p eriop erative p erip heral neu rop athies: a rep ort by the
Am erican Society of Anesthesiologists Task Force on Prevention of 227. Lee LA. ASA p ostoperative visu al loss registry: p relim inary analysis
Periop erative Perip heral N eu rop athies. Anesthesiology 2000;92(4): of factors associated w ith sp ine op erations. ASA Newsl 2003;67(6):
1168–1182. 7–8.
220. Warner MA. Periop erative neu rop athies. Mayo Clin Proc 1998;73(6): 228. Lee LA, Dom ino KB. Th e Closed Claim s Project. H as it influ en ced
567–574. anesthetic p ractice an d ou tcom e? In : Weber S, ed . Anesthesia-
221. Prielip p RC, Morell RC, Bu tterw orth J. Ulnar nerve inju ry and p eriop- related complications. Philad elp h ia, PA: W.B. Sau nd ers; 2002:247–
erative arm p ositioning. In: Weber S, ed . Anesthesia-related complica- 263.
tions. Philad elp hia, PA: W.B. Sau nd ers; 2002:351–365, vii–viii. 229. Cheney FW, Posner KL, Cap lan RA. Ad verse resp iratory events infre-
222. Warner MA, Warner ME, Martin JT. Ulnar neu rop athy. Incid ence, ou t- qu ently lead ing to m alp ractice su its. A closed claim s analysis. Anes-
com e, and risk factors in sed ated or anesthetized p atients [com m ent]. thesiology 1991;75(6):932–939.
Anesthesiology 1994;81(6):1332–1340. 230. Crosby ET, Lui A. The ad u lt cervical sp ine: im p lications for airw ay
223. Roth S, Gillesberg I, ed s. Injuries to the visual system and other sense m anagem ent. Can J Anaesth 1990;37(1):77–93.
organs. 2nd ed . St. Lou is, MO: Mosby; 1999. 231. Sp itellie PH , H olm es MA, Dom ino KB. Aw areness d u ring anesthesia.
224. Roth S, Thisted RA, Erickson JP, et al. Eye inju ries after nonocular su r- In: Weber S, ed . Anesthesia-related complications. Philad elp hia, PA: W.B.
gery. A stud y of 60,965 anesthetics from 1988 to 1992. Anesthesiology Sau nd ers; 2002:317–332, vii.
1996;85(5):1020–1027. 232. Sp inler SA, Dager W. Overview of hep arin-ind u ced throm bocytop e-
225. Gild WM, Posner KL, Cap lan RA, et al. Eye inju ries associated w ith nia. Am J Health Syst Pharm 2003;60 (Su p p l 5):S5–S11.
anesthesia. A closed claim s analysis [com m ent]. Anesthesiology 1992; 233. Porsche R, Brenner Z. Allergy to p rotam ine su lfate. Heart Lung
76(2):204–208. 1999;28(6):418–428.
226. N ew m an N J. Periop erative visu al loss after nonocu lar su rgeries. Am J 234. Corm ack JG, Levy JH . Ad verse reactions to p rotam ine. Coron Artery
Ophthalmol 2008;145(4):604–610. Dis 1993;4(5):420–425.
CHAPTER
13
Complications of Wound Healing

Michael G. Franz
Wou nd healing failu re is the m echanism of m any su rgical system ic circu lation. Fibrinogen extravasates from d is-
com plications. Incom plete tissu e rep air lead s to incisional ru p ted blood vessels and fills the gap of the w ound . The
hernias and anastom otic leaks, w hile excessive tissu e coagulation cascad e is activated and sustained through
repair resu lts in burn w ou nd contractures and lu m inal throm bin-m ed iated cleavage of fibrinogen, lead ing to the
strictu res. Dysregu lated w ound healing, therefore, is a form ation of fibrin m onom ers that p olym erize into an
com m on cau se of poor su rgical ou tcom es. Althou gh insolu ble fibrin clot to p revent fu rther bleed ing. The fibrin
w ound s are m ost frequ ently und erstood to m ean inju ries netw ork also establishes the provisional m atrix that allow s
to the skin, p racticing surgeons appreciate the im portance migration of m onocytes, fibroblasts, and end othelial cells
of w ou nd s and w ou nd ing to all types of tissue. The cellu lar into the w ou nd . Fibroblasts w ithin the fibrin clot synthe-
and m olecu lar p athw ays by w hich all typ es of injured tis- size collagen, and the fibrin matrix is progressively
sues heal share com m on integrated com ponents. A basic d egrad ed and replaced w ith a collagen-rich scar (2). Fibrino-
u nd erstand ing of the biologic mechanism s of tissue rep air gen has also been rep orted to ind u ce angiogenesis. Other
is necessary to p revent or treat the com p lications of w ou nd med iators activated d u ring hem ostasis such as p latelet-
healing. d erived grow th factor (PDGF) and throm bin p ep tid es have
overlap p ing regu latory effects on m any of the cellu lar ele-
■ NORMAL WOUND HEALING ments of early tissu e rep air, su ch as fibroblasts and
end othelial cells (3).
A w ou nd initially is tissu e that has lost norm al stru ctu re
and fu nctions follow ing the transfer of internal or external
kinetic, chem ical, or therm al energy. Wound healing is the
■ Inflammation
sequence of cellu lar and m olecular events activated at the
time of inju ry resulting in a tim e-d ep end ent pattern of tis- The cellular and hum oral inflam m atory phase is activated
sue repair (1). The integration of each com ponent pathw ay soon after w ou nd ing, and an im m u ne barrier is established
along the continu u m of the host resp onse to inju ry resu lts against p athologic m icroorganism s. Althou gh m ost acu te
in com p lete w ou nd healing (Fig. 13.1). Classically, the su rgical w ou nd s are sterile, chronic w ou nd s may be colo-
p hases of w ou nd healing are d escribed as hem ostasis, nized or infected w ith bacteria. Wou nd healing w ill be sig-
inflam m ation, fibrop roliferation, and rem od eling (m atu ra- nificantly im p aired if w ou nd tissu e bacterial levels exceed
tion). 105 organism s p er gram of tissu e (4). The red u nd ancy of the
signals for the w ou nd inflam m atory resp onse and w ou nd
healing is beginning to be d escribed . N ecrotic tissu e locally
■ Hemostasis releases cellu lar breakd ow n p rod u cts cap able of m ain-
The cellu lar and m olecular stru ctu re of the acute w ound taining and am p lifying the early inflam m atory resp onse
m atrix changes continu ou sly throu gh w ou nd m atu ration follow ing inju ry. Eicosanoid s, 20-carbon m etabolites of
and rem od eling. The d ynam ic process involves m olecu lar arachid onic acid d erived from cell-m em brane fatty acid s,
and cellu lar interactions d u ring w hich the initial fibrin-rich fu nction as p rim ary m ed iators in the w ou nd healing
clot is transform ed into a collagen-rich scar. Before a schem e. Macrop hages are tissu e leu kocytes fu nd am ental to
w ound can heal it m u st stop bleed ing. Therefore, the earli- the inflam m atory resp onse follow ing inju ry, w hich pro-
est p hase of w ou nd healing follow ing inju ry is character- vid es an abu nd ant reservoir of p otent tissu e grow th factors
ized by the d ep osition of fibrinogen, a solu ble p lasm a necessary for rep air, su ch as transform ing grow th factor-
p rotein synthesized by the liver and secreted into the (TGF- ). The intensity of the early inflam m atory response
is greater in ad u lt w ou nd healing, in w hich p rotection
against microbial insu lt su p p orts tissu e rep air. Du ring fetal
w ou nd healing u ntil m id gestation, the intensity of this tis-
Michael G. Franz: University of Michigan, Ann Arbor, MI su e inflam m atory resp onse is significantly red u ced . One
48109. p roposed m echanism is im m atu rity of the cellu lar im m u ne
128
Chapter 13 • Complications of Wound Healing 129
FIGURE 13.1. Functional acute wound healing requires the

coordinated activation of cellular and molecular repair path-
ways beginning at the moment of injury. Each component must
then be integrated into a continuum during the host response.
For surgical incisions, it is the rate of recovery in breaking
strength that determines the outcome of the acute wound.
system and red uced grow th factor prod uction (5). The response. In neutrophil-depleted animal models, it has been
blu nted im m ed iate tissu e inflam m atory response in utero is show n that neu trop hils are not m and atory for the progres-
one p otential exp lanation for the p henom enon of scarless sion of norm al tissu e rep air (3). H ow ever, it is also w ell
fetal healing. know n that if a w ou nd infection d evelop s, healing w ill be
Over the p ast d ecad e, the free rad ical nitric oxid e (N O) d elayed . In p atients w ith chronic granu lom atou s d isease in
has em erged as a fu nd amental signaling m olecule for w hich an absence of the enzym e N ADPH -oxid ase occu rs,
many biologic p rocesses (6,7). N O has proven esp ecially the intracellu lar killing of bacteria and fu ngi w ithin neu -
im portant in physiologic responses im portant to su rgeons, trop hils is im p aired . This d efect resu lts in chronic infec-
such as follow ing trau m atic injury and d uring sep sis. N O tions, w hich retard the rep air p rocess.
level and activity is central to the regu lation of vascu lar Follow ing burns, there is d elayed tissue necrosis second -
tone d u ring shock and is equ ally im p ortant as a m etabolite ary to vascular occlusion caused by thrombi deposition in
that can establish a host barrier against m icroorganism the vascular bed surround ing the burn w ound . The absence
invasion. of blood flow through these vessels results in extend ed tis-
N O is synthesized by one of three isoform s of nitric sue necrosis and an increase in the w ound surface area. Pre-
oxid e synthase (N OS). Ind u cible N OS (iN OS) is u p regu - venting the infiltration of circulating neutrophils into a burn
lated follow ing tissu e injury. Most d ata suggest that local w ound using blocking antibod ies d irected against neu-
N O p rod u ction prom otes norm al w ou nd healing. N OS trophil surface antigens has been show n in animal mod els to
inhibitors d elay the healing of acu te excisional w ound s, prevent the development of secondary burn necrosis. Obser-
w hile su p p lem ental N O p rovid ed via m olecu lar d onors vations such as these d emonstrate that a balance betw een
accelerates acu te w ound healing. The recovery of incisional w ound benefit and w ound d etriment exists and that exces-
w ou nd breaking strength is also d elayed follow ing N OS sive neutrophil-d erived factors such as oxygen rad icals can
blockad e. Knockou t m ice m issing the iN OS gene exhibit actually impede tissue repair.
marked im p airm ent of acu te healing that can be reversed Circu lating m onocytes enter the w ou nd in a second
by iN OS gene transfer. It appears that N O contribu tes to w ave of inflam m atory cells w ithin 24 hours after the
acu te tissu e rep air by p rom oting collagen synthesis and ap p earance of neu trop hils (1). Monocytes term inally d iffer-
angiogenesis (8). entiate into tissue m acrophages u pon exiting the vascula-
Once bleed ing is controlled , the increased permeability tu re and entering the w ou nd site. Macrophages are
of vessels ad jacent to the injury facilitates the migration of clearing hou ses for m any im p ortant m olecu lar signals for
inflam m atory cells into the w ou nd . Polym orphonu clear the p rop agation of the w ou nd rep air p rocess, such as oxy-
leu kocytes (neu trophils) are the pred om inant initial inflam - gen free rad icals, inflam m atory cytokines, and tissu e
matory cell p opu lation to enter the w ound site. The rise in grow th factors. Tissu e m acrop hages also have the capacity
w ound neutrophil number begins almost immed iately fol- to u nd ergo cell d ivision w ithin the w ou nd site and , like
low ing inju ry and peaks by p ostinju ry d ay 2. The prim ary the neu trop hils, can clear the w ou nd of contam inating
function of acute w ound neutrophils appears to be phago- m icrobes as w ell as nonviable tissu e. Macrop hage synthe-
cytosis of invad ing microbes and release of cytochemoat- sis and release of tissu e grow th factors is a p red om inant
tractants to further propagate the cellular inflammatory signal m echanism for the initiation of the p roliferative
phase of the rep air process. Macrophage-d erived grow th TGF- , (TGF- ), and bFGF. As acu te tissu e rep air p roceed s
factors prom ote the m igration of synthetic cells into the and m acrop hage nu m ber d ecreases, other cells in the
w ou nd site and the p rod u ction of a new connective tissu e w ou nd su ch as fibroblasts, end othelial cells, and ker-
matrix (1). The regu lated progression from a controlled tis- atinocytes begin to synthesize and secrete grow th factors.
su e inflam m atory resp onse to an efficient fibrop lastic Fibroblasts secrete bFGF, TGF- , PDGF, insu lin-like grow th
phase is requ ired for norm al healing. factor (IGF-I), and keratinocyte grow th factor (KGF).
End othelial cells p rod u ce vascu lar end othelial grow th fac-
■ Fibroproliferation and remodeling tor (VEGF), bFGF, and PDGF. Keratinocytes synthesize
TGF- , TGF- , and KGF. These grow th factors together
Once hem ostasis is achieved , ongoing inju ry has ceased , stim u late continu ed acu te w ou nd cellu lar p roliferation,
and an im m u ne barrier is in p lace, w ou nd healing trajec- p rod u ction of extracellu lar m atrix p roteins and glycop ro-
tories shift tow ard fibrop lasia and tissu e rep air. In ad u lts, teins, and angiogenesis.
the m echanism of tissu e rep air favors the rap id establish- Fibroblasts requ ire a scaffold or m atrix to specifically
m ent of m echanical integrity over stru ctu ral and fu nc- bind to and m ove across to enter the acute w ou nd environ-
tional tissu e regeneration. Scar tissu e rep laces norm al m ent and initiate tissu e rep air. Extracellu lar hyaluronic
tissu e follow ing inju ry and is often a sou rce of su bsequ ent acid p rom otes cell m igration and p roliferation early in the
w ou nd com p lications. Tissu e regeneration follow ing rep air p rocess (10,11). Soon after, a falling hyalu ronic acid
inju ry occu rs only in select ad u lt stru ctu res, su ch as the concentration in the acu te w ou nd and rising chond roitin
liver, or in relatively sm all su rface area ep id erm al w ou nd s. sulfate levels inhibit fibroblast m igration and proliferation
Over tim e, w ou nd m atrix cell nu m ber d im inishes and col- and ind u ce fibroblast d ifferentiation and m atu re connec-
lagen bu nd les are increasingly organized d u ring rem od - tive tissu e synthesis. Unlike u nw ou nd ed d erm al fibrob-
eling. This final p hase of w ou nd healing can continu e for lasts, granu lation tissu e fibroblasts organize intracellular
years u ntil a m axim u m w ou nd strength p lateau is finally actin m olecu les into p olymers, a featu re of m any m igrating
reached . cell typ es.
The proliferative phase of acute tissue repair begins with When acu te w ou nd fibroblasts reach a high d ensity and
the arrival of fibroblasts into the wound site on about postin- cell–cell contact inhibition occurs, the polymerized intracel-
jury day 2 or 3. Fibroblasts work to replace the fibrin-based lular actin chains cond ense into cytoplasmic stress fibers
provisional matrix established during the inflammatory or that have been show n to contain -smooth muscle actin.
lag phase of tissue repair w ith a collagen-rich granulation tis- These w ou nd fibroblasts staining for -smooth muscle actin
sue that is characteristic of the proliferative phase. Fibroblasts are named myofibroblasts (11,12). It is controversial
also synthesize and release glycosaminoglycans and proteo- w hether myofibroblast contraction is the d ominant mecha-
glycans that are important components of the extracellular nism by w hich the healing acute w ound und ergoes subse-
matrix of granulation tissue. Simultaneously, vascular regen- quent contraction. It has been show n both in vivo and in
eration (angiogenesis) is occurring, using the maturing vitro that m yofibroblasts m ight not be necessary for w ound s
matrix as a scaffold. The newly formed vascular cond uits to contract (13). Other stud ies have show n that cell-traction
supply nutrient building blocks to the cellular elements of the forces on the w ound matrix generated by activated fibrob-
granulation tissue. In dermal wounds, overlying epidermal lasts through the action of cytoplasmic fine actin filaments
cells begin to migrate across the tissue defect at about this are responsible for w ou nd contraction. The myofibroblast
time to restore the skin’s epithelial barrier function. Although might be a terminally d ifferentiated fibroblast preparing for
inflammatory cells provid e the initial defense against micro- ap optosis (programmed cell d eath) rather than a u niqu e cell
bial invasion follow ing injury, surface coverage ultimately type necessary for w ou nd contraction.
provid es this protection. Collagen is the m ajor protein com ponent of w ou nd con-
The m igration and p roliferation of fibroblasts into the nective tissu e. Mod ifications of the chem ical com position
acu te w ou nd is in large p art signaled by p otent tissu e of collagen d eterm ine its biologic fu nction. Mu ltiple iso-
grow th factors inclu d ing PDGF, TGF- , and basic fibrob- forms of collagen, each the p rod u ct of a u niqu e gene, have
last grow th factor (bFGF) (9). Fibroblasts begin to m igrate been d escribed (14). The connective tissu e collagens are all
into the w ou nd as soon as 2 d ays follow ing inju ry. After 4 helical in stru ctu re, w ith the d istinctive rep eating trip ep-
d ays, fibroblasts are the m ajor cell typ e in the d evelop ing tid e sequ ence of glycine-X-Y, w ith the Y p osition u sually
granu lation tissu e. At first, the w ou nd fibroblast nu m ber occu p ied by p roline or hyd roxyp roline. Glycine and pro-
increases via m igration from ad jacent u nw ou nd ed tissu e, line am ino acid s are requ ired for m atu re collagen m ole-
bu t soon the w ou nd fibroblast p op u lation rap id ly cu les to assu m e tertiary trip le helical stru ctu re. Different
increases fu rther by cell p roliferation. The acu te w ou nd isoform s of collagen are exp ressed in d ifferent tissu es and
fibroblast d ensity is m axim ized betw een 7 and 14 d ays tissu e locations at variou s tim es d u ring healing. Typ e I col-
after inju ry and is u nd er the p otent influ ence of w ou nd lagen is the p red om inant typ e in bone and tend on. Typ e III
grow th factor levels. Activated tissu e m acrop hages are a and typ e I collagens are p resent in m ore elastic soft tissu es,
p rim ary sou rce for the variou s grow th factors, inclu d ing su ch as blood vessels, d erm is, and fascia. Unw ou nd ed
d erm is contains approxim ately 80% type I collagen and d ensity of m acrop hages and fibroblasts is red uced . Fibrob-
20% typ e III collagen. Acu te w ou nd granulation tissu e, in last and m yofibroblast term inal d ifferentiation and subse-
contrast, exp resses tw ice as m uch type III collagen. Typ e III qu ent apop tosis is the m echanism by w hich m atu ring
collagen is consid ered “im m ature” and is less cross-linked w ou nd fibroblast nu mber is red u ced . After skin healing,
than m atu re typ e I collagen, w ith a low er resulting tensile the ep id erm is of the resu ltant scar d iffers from u ninju red
strength. skin becau se it lacks the rete p egs that norm ally anchor into
N orm al collagen synthesis and secretion requires the u nd erlying connective tissu e m atrix. There is also no
hyd roxylation of lysine and proline resid ues. The cofactors regeneration of lost su bep id erm al ap p end ages su ch as hair
necessary for enzym atic collagen hyd roxylation are ferrou s follicles or sw eat gland s follow ing skin healing. Eventu ally,
iron, m olecu lar oxygen, -ketoglu tarate, and vitamin C. angiogenesis d im inishes, w ou nd blood flow falls, and
Im p aired w ou nd healing resu lts from d eficiencies in any of m etabolic activity slow s.
these cofactors, as d u ring tissu e hypoxia or w ith d iets low Fibroblasts then fu rther consolid ate thin collagen fiber
in vitam in C. After synthesizing and releasing collagen, bu nd les into thick collagen cables. There is a change in scar
w ou nd fibroblasts w ork to organize new extracellu lar col- tissue collagen comp osition, as the immature collagen III
lagen m olecules into fibers oriented betw een sp ecialized levels fall from 30% to 10% in m atu re scar (17). Finally,
intercellu lar ju nctions. Fibrillar collagen is m ad e even m ore w ou nd contraction occu rs. Fibroblasts pack collagen fibers
insoluble throu gh the covalent cross-linking of collagen as a contractile u nit. Cells and matrix generated w ithin the
pep tid es located at the nonhelical end s of the m olecu le. w ound site prod uce force vectors d irected to achieve a fur-
The interstitial enzym e lysyl oxid ase catalyzes this late- ther red u ction in w ou nd volume. Id eally, as w ou nd contrac-
stage p athw ay (15). tion proceed s, the injured tissue is replaced by uninjured
The organization of collagen bu nd les in the acu te surround ing tissue.
w ou nd and in u nw ou nd ed d erm is is d ifferent. Collagen
fiber bu nd les are arranged in a m esh like, basket-w eave
p attern in u nw ou nd ed d erm is, w hile in acu te w ou nd
■ The lag phase of wound healing
granu lation tissu e m atu re collagen fibers are oriented in Recru iting the cellu lar and m olecu lar elem ents of tissu e
overlap p ing arrays p arallel to the w ou nd su rface and rep air into the w ou nd site takes tim e. The “lag phase” of
u su ally along lines of m axim u m tension. The p arallel w ound healing is d efined as the earliest period of tim e fol-
array arrangem ent of granu lation tissu e collagen and of low ing w ou nd ing w hen hem ostasis, inflam m ation, and
m atu re scar contribu tes to the abnorm al com p liance of early fibrop lasias are ind u ced . It is d u ring the lag phase of
scar tissu e. w ound healing that acute w ou nd s are m ost vu lnerable to
The d elivery of nutrient synthetic components is m echanical failu re (d ehiscence). The w ound tensile
required for acute w ound healing to progress. Initially, there strength is 0% to 30% of its m axim u m valu e d u ring the first
is no vascular supply to the wound center and the appear- 7 d ays follow ing w ou nd ing. This interval is the tim e d ur-
ance of new, viable tissue is limited to wound margins that ing w hich p atients are increasing w ou nd load s.
are in contact with uninjured tissue. The formation of new Epithelialization involves the proliferation and m igration
blood vessels in acute granulation tissue (angiogenesis) of ep ithelial cells, m ost often referring to keratinocytes. The
occurs by a bud d ing or sprouting mechanism from intact p rocess com pletes w ou nd coverage over a bed of granu la-
vessels at the w ound bord ers. The development of vascular tion tissue or over a partial thickness inju ry to an epithelial-
outgrow ths requires end othelial cell proliferation. N umer- ized stru ctu re like the skin or gastrointestinal (GI) m ucosa.
ous tissue grow th factors, such as VEGF and bFGF, play cen- Rep air ep ithelial cells are d erived from the w ou nd p erip h-
tral regulatory roles in neovascularization and subsequent ery from u ninju red ep itheliu m or from sp ecialized su bep -
tissue repair (16). Macrophages are necessary for w ound ithelial stru ctu res like hair follicles and sw eat gland s in the
neovascularization. skin. In incisions, this d istance is very short and the estab-
The acute granulation tissue that replaces the fibrin- lishm ent of ep ithelial coverage shou ld be com p leted w ithin
based p rovisional matrix is a transitional tissue, and w hen it d ays ep ithelialization contribu tes nothing to the gain in
matu res it usually prod uces scar. Acute w ound granulation w ou nd breaking strength—an im p ortant p rocess that is
tissue is the result of the processes of inflammation, fibro- slow to initiate and continu es for long after the w ou nd has
plasia, angiogenesis, and extracellular matrix synthesis. It is been resu rfaced . Follow ing acu te d ermal injury, su ch as
characterized by a high d ensity of capillaries, fibroblasts, bu rns, the early closu re of an op en w ou nd by ep ithelializa-
macrophages, and loosely organized thin collagen fibril tion initiates the w ound rem od eling process w ithin the
bu nd les. The metabolic activity of acute granulation tissu e u nd erlying granu lation tissu e. N u m erou s m od els have
is high, as rapid cell proliferation proceed s synchronously d escribed the m olecu lar signaling that occu rs betw een
w ith high-level protein synthesis as w ell as lactate and CO 2 regenerating epithelial stru ctu res and the und erlying su p-
prod u ction. p orting m esenchym al tissu e. Early w ou nd su rface cover-
When the w ound d efect is filled and as tim e p asses, the age red u ces the likelihood of d isabling hyp ertrophic scar
matu ring granu lation tissu e u nd ergoes rem od eling. The form ation and im p roves the overall cosm etic result. When
Table 1 3 .1 Im p ed im en t s t o wou n d h ea lin g

Systemic Local
Malnutrition Contamination and infection
Chronic diseases Repeated trauma
Drugs Tissue hypoperfusion
Shock Irradiation
Age Neoplasm
FIGURE 13.2. Wound healing failure occurs when an impediment to normal Genetic repair defects Factitious wounding
repair pathways results in an abnormality in the quality or duration of the
sequential components of tissue repair. The obstacles to normal wound heal-
ing might be biologic or mechanical in origin and might derive from the
wounded host or from external forces.
m atrix and synthesis of im m atu re scar. Ep ithelialization
requ ires an u nd erlying fu nctional bed of granu lation tis-
su e. Obstacles to norm al w ou nd healing therefore shift
the w ou nd su rface area is small, regenerative reepithelial-
the w ou nd healing trajectory and resu lt in w ou nd com p li-
ization might occur with little or no scar formation.
cations (Fig. 10.2).
Contraction is a m etabolically active m echanism by
w hich w ou nd volu m e is m echanically d im inished .
Although the m echanism of w ound contraction is com plex,
it appears to involve tractional forces generated by rep air ■ PREOPERATIVE RISK FACTORS FOR
fibroblasts transm itted to the w ound extracellular m atrix WOUND COMPLICATIONS
via cellular adhesion molecules (13). The early wound matrix
is composed in large part of collagen, fibrin, fibronectin, and
■ Contamination and infection
vitronectin. Intracellular fibroblast cytoskeletal polymeriza- The risk factors for su rgical w ound com plications can be
tion, an energy requiring process, is the source of the trac- broad ly categorized as local or system ic w ou nd healing
tional forces. Some evidence also suggests that terminally im p ed iments (Table 13.1). The m ost com mon local risk fac-
differentiated wound fibroblasts, called myofibroblasts, are tor is w ou nd contam ination or infection. The risk for
involved. These cells express cytoplasmic smooth muscle w ound contam ination and infection can be pred icted by
actin and are contractile. categorizing su rgical w ou nd s accord ing to clinical circu m -
Wound failure occurs w hen there is an abnormality in stances. In increasing ord er of risk for w ou nd infection,
the m agnitu d e or d u ration of the sequ ential com p onents of they are op erating in (i) a clean field , (ii) a clean-contam i-
tissu e rep air. Inad equate hem ostasis d ue to p latelet d ys- nated field , (iii) a contam inated field , and (iv) an infected or
fu nction or poor techniqu e resu lts in hem atom a form ation d irty field (Table 13.2). A clean op erative field m inim izes
w ith ensu ing m echanical d isru p tion of the p rovisional w ound bacterial exp osu re by operating upon otherw ise
w ound matrix. Delayed or d eficient inflamm atory responses norm al and healthy soft tissu e u su ally breaching only the
increase the risk of w ound contamination or infection. A pro- skin. The bacterial organism s norm ally colonizing skin sur-
longed inflammatory response d ue to foreign material d elays faces are p red om inantly Gram -p ositive Staphylococcus and
the progression of tissue repair into the fibroproliferative Streptococcus sp ecies. Follow ing stand ard op erative field
phase in w hich rapid gains in breaking strength and wound sterile p rep aration, exp ected w ou nd infection rates in this
contraction should occur. Imp aired fibroblast activation in setting are 1% to 3% (18,19). Exam p les inclu d e breast biop-
tu rn im p ed es the establishm ent of the early w ou nd sies and ingu inal hernia rep air. An op eration is classified
Table 1 3 . 2 Risk for wou n d con t a m in a t ion a n d in fect ion a ccord in g t o

clin ica l cir cu m st a n ces
Wound Classification Examples Risk for Wound Infection (%)
Dirty/infected with Infected traumatic wound 60
necrotic debris
Contaminated Gunshot wound to left colon 33
Clean-contaminated Elective colon resection 5
Clean Breast biopsy or hernia repair 1
clean contam inated if an organ that is colonized w ith high com p lement, both im p ortant chemotactic factors for fibro-
nu m bers of p otentially p athologic bacteria is exp osed to blasts and m acrop hages. Decreased p olym orphonuclear
the w ou nd . Com m on exam p les are colorectal and p u l- leu kocyte activity against fu ngi and bacteria has been
m onary resections. In this setting, exp ected w ou nd infec- m easu red in child ren su ffering kw ashiorkor p rotein d efi-
tion rates are red uced to 10% w ith appropriate preop erative ciency (23). Prolonged p rotein m alnu trition lim its collagen
preparation and p rophylaxis. A proced ure is classified as synthesis, fibroblast p roliferation, and neovascu larization.
contaminated if high-level, uncontrolled bacterial contam i- Althou gh nu tritional statu s is d ifficu lt to m easu re in
nation occu rs, esp ecially w hen associated w ith local tissu e most clinical settings, a serum albumin 3 g per d L increases
necrosis or ischem ia. Exam p les of these p roced u res the risk of w ou nd infection and incisional hernia form a-
inclu d e rep air of gu nshot w ou nd s of the colon or severe tion. A large Veterans Ad m inistration coop erative stu d y of
bu rn inju ries. Wou nd infection rates in these settings are p eriop erative risk factors fou nd that a low p reop erative
33% to 60% (18). seru m albu m in level w as the single m ost significant vari-
N ecrotic tissue exacerbates d efective w ou nd repair. able for p red icting su rgical m orbid ity (20). Wou nd infec-
Bacteria u se necrotic d ebris as a nutrient source, increasing tion and acu te w ou nd failu re w ere am ong the m ost
the likelihood of invasive w ound infection. Metabolites of com m only observed com p lications. Protein synthesis and
cell-m em brane arachid onic acid released from d ying cells cell d ivision are stim u lated at w ou nd sites, and an abu n-
are toxic to ad jacent norm al cells. N ecrotic d ebris w ithin d ant su p p ly of am ino acid s is necessary to su stain rep air.
the w ou nd also establishes a m echanical barrier against the Fatty acid d eficiencies are know n to cau se d elayed d erm al
influx of wound repair cells, such as fibroblasts and ker- healing. Cancer cachexia is associated w ith p rofou nd
atinocytes. Tissue proteases released by necrotic cells d elays in w ou nd rep air. Elevated circu lating cytokine lev-
degrad e w ou nd grow th factors, preventing the initiation of els, su ch as tu m or necrosis factor- , contribu te throu gh
grow th factor-d epend ent repair p athw ays. d istu rbances in the norm al w ou nd inflam m atory resp onse.
Micronu trient d eficiency can also imp air w ou nd heal-
ing. Vitam in A is a cofactor for norm al cell d ifferentiation
■ Tissue hypoperfusion and ep ithelial keratinization. Vitam in C is critical for
Operating d uring period s of shock increases the risk of sur- strength gain in healing w ou nd s, catalyzing the hyd roxyla-
gical w ound failure. Wound infection and d ehiscence rates tion of p roline and lysine resid u es d u ring collagen cross-
increase threefold w hen operating during profound linking. Vitam in K is requ ired for the synthesis of several
hypotension and acidosis (20). Tissue perfusion is impaired coagu lation p roteins, inclu d ing p rothrombin. Deficiencies
as a consequence of other d isorders, includ ing peripheral are therefore associated w ith excessive bleed ing from
vascular d isease, edema, hypothermia, vasospastic d isease, w ou nd ed tissu e and abnorm al p rovisional m atrix form a-
and venous hypertension. Irradiated tissue is also hypoper- tion. Trace m ineral d eficiencies can d evelop in su rgical
fused as the result of microangiopathy. Previously irrad iated p atients, esp ecially those treated w ith p rolonged par-
tissue m ight be especially susceptible to w ound necrosis enteral nutrition and in patients w ith chronic cond itions
given its red uced capillary blood supply and increased su ch as alcoholism , GI d isord ers, and d iabetes. Zinc acts as
fibrosis, w hich results in an abnormal w ound inflammatory a cofactor to m any enzym atic reactions involved in DN A
response. synthesis, p rotein synthesis, m itosis, and cellu lar prolifera-
Red u ced cap illary p erfu sion resu lts in a low tissu e tion. Red u ced zinc levels resu lt in d elayed ep ithelialization
oxygen tension, w hich is associated w ith collagen d efects and fibroblast p roliferation. Iron is a cofactor in collagen
an d in creased w ou nd infections (21). Severe isch em ia synthesis, and low iron levels ind irectly im pair healing
an d hyp oxia can d irectly inh ibit other w ou n d healing becau se of red u ced oxygen transp ort.
p rocesses su ch as angiogenesis an d ep ithelialization .
Transcu tan eou s tissu e oxygen m on itors p rovid e a clini-
cally available m eans for m easu ring w ou nd oxygen lev-
■ Chronic diseases
els. Chronic w ou nd s like p ressu re u lcers and d iabetic Und erlying d isease in the injured host can com plicate
foot u lcers d o not heal w hen tissu e oxygen levels fall below w ou nd healing. Diabetes m ellitu s is know n to d elay the
30 m m H g. closure of d ermal foot ulcers, but it is not clear that incisional
healing is d elayed in d iabetic p atients. Diabetic p atients are
m ore su scep tible to w ou nd infection becau se of im p aired
■ Malnutrition neu trop hil chem otaxis and p hagocytosis. The clean w ound
Severely m alnou rished or catabolic patients, as d u ring the infection rate is higher in d iabetic p atients (11%) than in the
system ic inflam m atory response synd rom e, d em onstrate general p atient p op u lation (24).
im p aired healing (22). The d eleteriou s effects of m alnu tri- Increasing p atient age is not a consistent risk factor for
tion are exp ressed in each of the p hases of w ou nd healing. global w ou nd healing com p lications. There ap pears to be a
An altered inflam m atory response m ight resu lt from the m inor d efect in ep id erm al-d erm al rep air that is the resu lt
effects of m alnu trition on im m u ne fu nction. Anim als fed of changes in tissu e extracellu lar m atrix stru ctu re and
protein-free d iets d evelop red uced levels of fibronectin and resu ltant elasticity of aged skin, bu t this d oes not ap pear to
affect m yofascial, GI, or vascular repair. In sp ecific m od els, Cytotoxic agents can ind u ce p rofou nd d elays in w ou nd
increased host age is associated w ith im paired w ou nd heal- rep air by inhibiting cell p roliferation, DN A, and protein
ing. Fibroblast p roliferation and activity are d im inished synthesis. Chem otherap eu tic d ru gs m ight su p p ress the
and collagen p rod u ction and w ound contraction are norm al w ound inflam m atory response as w ell as inhibit
slow ed d ow n (23). Tissue repair observed in the eld erly is fibroblast p roliferation and collagen d ep osition. Clinically,
often com p licated by an increased incid ence of com orbid it is usual to d elay ad m inistration of an antineop lastic
cond itions and polypharm acy. agent in a p ostop erative cancer p atient u ntil the acu te
Im m u nod eficiency states have been associated w ith w ou nd healing p hases are com p leted becau se of concern
d elayed w ou nd healing. In the presence of an imp aired for ad verse d ru g effects on w ou nd healing (u su ally 3 to
im m une d efense, w ou nd bacterial load s m ight rise to 6 w eeks).
uncontrolled levels and d elay healing trajectories. Althou gh
polymorp honuclear leukocytes are not absolutely requ ired
for w ound healing, the absence or red uction in w ound
■ Genetic defects
macrophage number or activity lead s to significant impair- The classic genetic d isord er w ith an abnorm al w ou nd
ment of tissue repair (1). healing p henotyp e is the Ehlers–Danlos synd rom e. Vari-
Acu te and chronic liver d iseases are associated w ith able p enetrance of the d efective stru ctu ral p rotein genes
d elays in w ou nd healing. In anim al m od els, acu te jau nd ice m ight cau se su btle clinical p resentations. There are at
cau sed a 25% to 50% red u ction in abd om inal incision least 12 d istinct su btyp es of Ehlers–Danlos, and althou gh
bu rsting strength after 1 w eek (1). Long-stand ing jau nd ice it is infrequ ent, encou ntering su ch a p atient occu rs in
had less of an inhibitory effect on healing incisions. Clini- m ost su rgical careers. Ehlers–Danlos synd rom e is often
cally, increased fascial d ehiscence has been rep orted fol- associated w ith fragile skin, w eakened scar and w ou nd
low ing lap arotom y p erform ed in jau nd iced p atients, d isru p tion, sp ontaneou s aneu rysm s in m ajor blood ves-
esp ecially those w ith m alignant cau ses for jau nd ice. Acu te sels, and bleed ing d isord ers. A carefu l p ersonal and fam -
w ou nd failu re rates of 60% have been observed in sm all ily history as w ell as p hysical exam shou ld alert the
series. observant su rgeon to these d isord ers. Other frequ ently
encou ntered p atients w ith d isord ered w ou nd healing
inclu d e Marfan’s synd rom e p atients. N ew er genetic and
■ Drugs biochem ical evid ence su ggests that sp ontaneou s abd om i-
Cytotoxic and m etabolically active pharm acologic agents nal aortic aneu rysm p atients m ight also exp ress abnorm al
shou ld alw ays be consid ered w hen m anaging a w ou nd . content or collagen p rotease activity contribu ting to both
The active cellu lar com ponents of w ou nd healing, su ch as arterial w all w eakness and d efective w ou nd healing.
macrop hages, fibroblasts, and ep ithelial cells, are targets Abd om inal aortic aneu rysm p atients are com m only
for und esirable inhibitory sid e effects. Althou gh there are encou ntered in su rgical p ractices. Once a clinical d iagno-
not m any class one d ata sets proving the im pairm ent of tis- sis associated w ith d efective tissu e rep air is m ad e, great
sue rep air by m ost pharm acologic agents, clinical exp eri- care m u st be exercised in w ou nd closu re and m anage-
ence and pharm acologic m echanism s should alert all m ent, since there are no know n m ethod s for correcting the
clinicians m anaging w ou nd s to the possibility of d rug- d efective biochem ical p athw ays.
ind uced w ou nd com p lications.
It is n ot clear that corticosteroid u se d elays m ost soft
tissu e rep air follow ing su rgical w ou nd ing. Category II ■ MODIFICATION OF PREOPERATIVE
evid ence su ggests that ep id erm al rep air is d elayed , bu t RISK FACTORS
there is n o solid evid ence that m yofascial or GI healin g is
im p aired (25). Steroid s have been show n to inhibit
■ Minimize contamination
fibroblast fu nction in vitro. Althou gh the recovery of d er- Minim ization of m icrobial w ou nd contam ination low ers
m al ten sile strength is d elayed in rod ents treated w ith the incid ence of w ou nd infection and w ou nd failu re. Anti-
corticosteroid s at the tim e of incision, the effects of corti- sep tic p rep aration of the su rgical site is know n to red u ce
costeroid s on hu m an clinical w ou nd healing have not the incid ence of w ou nd infection follow ing clean cases. In
been w ell stu d ied . Mechanistically, it is likely that corti- the case of GI su rgery, p reop erative lu m inal m echanical
costeroid s im p air tissu e rep air throu gh their inhibitory and antibiotic p rep aration m ay red u ce exp osu re to enteric
effects on inflam m ation and stru ctu ral gene exp ression. bacteria and low er w ou nd infection rates, althou gh som e
The inh ibitory effect of cortisone on skin w ou nd strength stu d ies show no clinically significant benefit (18). Sharp
in rod ents is negated if vitam in A is given concu rrently. d ebrid em ent of necrotic tissue from acu te and chronic
N o d ata are available on the treatm en t of p atients on w ou nd s increases the incid ence of com p lete w ou nd heal-
steroid s w ith vitam in A p rior to su rgical w ou nd ing, ing (4). In the case of gross w ou nd contam ination, the
althou gh em p irical therap y m ight be reasonable. w ou nd shou ld be cop iou sly irrigated at the tim e of the
op eration to clear necrotic tissu e and foreign m aterial.
■ Antibiotics Delayed p rim ary closu re p rovid es an alternative. This

techniqu e involves leaving a contam inated w ou nd op en
Therap eu tic tissu e antibiotic levels at the su rgical site d u r- w ith m oist d ressing changes u ntil bacterial balance is
ing incision red u ce the incid ence of w ound infection fol- achieved . When qu antitative w ou nd cu ltu re levels fall to
low ing clean and clean-contam inated cases. This requ ires 105 colony form ing u nits p er gram of w ou nd tissu e, the
that a bolu s d ose of the appropriate antibiotic be given ju st w ou nd healing su ccess rate follow ing closu re ap p roaches
prior to the time of w ound ing. Antibiotics w ith a sp ectru m that of p rim ary closu re (1). Delayed p rim ary closu re also
of coverage for Gram -p ositive skin organism s are ind icated p rovid es the time necessary for the cellu lar and m olecular
for clean cases (e.g., first-generation cephalosp orin). An elem ents of tissu e rep air to enter the w ou nd p rior to
antibiotic class w ith broad er Gram -negative coverage is w ou nd closu re. Delayed p rim ary closu re is usu ally per-
ind icated for clean-contam inated GI cases (e.g., second - form ed 24 hou rs to several d ays follow ing injury.
generation cep halosp orin). It is not clear that antibiotic Tertiary w ound closu re involves the transfer of viable
ad m inistration follow ing grossly contam inated trau m atic au tologou s tissu e from a d istant site to the w ound . Partial
injuries low ers the incid ence of p ostoperative w ou nd infec- thickness skin grafting is a frequ ently u sed exam ple. The
tions. Becau se of the high incid ence of w ound infection fol- technique can accelerate epithelialization w hen w ound
low ing contam inated cases, antibiotics are typically begu n contraction has stop p ed or there is a large su rface area of
em pirically. granulation tissue.
The choice of su tu re m aterial d oes not significantly
■ Resuscitation affect w ou nd healing. In p rincip le, the su tu re should pro-
vid e app roxim ation of the inju red tissu e and m aintain
Transcu taneou s oxygen tension is the op tim al m ethod for bu rsting strength u ntil w ou nd m echanics recover. A very
m easu ring nu tritive skin p erfu sion and has a d irect corre- rap id ly absorbed su tu re m aterial w ou ld therefore be
lation w ith the su ccess of d erm al healing. Molecu lar oxy- ap p rop riate for a low load w ou nd rep air in w hich w ou nd
gen is necessary for m atu re collagen form ation, and tensile strength rap id ly recovers, su ch as follow ing corneal
op tim ized collagen fibril cross-lin kin g fails as tissu e keratotom y. In contrast, w ou nd closu re follow ing abd om i-
oxygen p ressu re (P O 2) levels fall below 40 m m H g. When nal w all lap arotom y requ ires a stou t su tu re m aterial that
periw ou nd P O 2 falls below 30 m m H g, healing m ay be m aintains its m echanical integrity for the 6 to 12 w eeks nec-
im p aired . Below 10 m m H g, oxygen is d eficient and essary for recovery of m axim al w ou nd bu rsting strength.
grow th factors have little chance of ind u cing healing m ech- Class 2 and 3 d ata su ggest that braid ed su tu re materials are
anism s for these w ou nd s. In most m od els, hyperbaric oxy- associated w ith higher su tu re abscess rates, especially
gen (H BO) therap y has been fou nd to im prove w ound w hen u sed in contam inated w ou nd s. Bacteria lod ge w ithin
oxygen d elivery and to ind u ce angiogenesis in ischem ic the interstices of braid ed su ture and escape w ou nd im m u ne
w ou nd s (21). cell p hagocytosis.
Acu te w ou nd failu re is m ost often d u e to su tu re
p u lling throu gh ad jacent tissu e and not su tu re fractu re or
■ Wound closure technique knot slip p age (25). Tissu e failu re occu rs in the biochem i-
Prim ary w ou nd closu re is d efined as the su rgical closu re of cally active zone ad jacent to the acu te w ou nd ed ge in
a w ou nd w ithin several hou rs after the w ou nd is m ad e. w hich p roteases activated d u ring norm al tissu e rep air
Prim ary w ou nd closu re resu lts in low infection and w ou nd resu lt in a loss of native tissu e integrity. This is esp ecially
failu re rates for clean and clean-contam inated w ound s. tru e for GI anastom oses in w hich a fall in w ou nd tensile
Whenever p ossible, incisions shou ld be placed in lines of strength has been m easu red d u ring the first 3 d ays follow -
minim al tension to prevent hypertrophic scarring. This is ing rep air (26–30). The breakd ow n of the tissu e m atrix
especially tru e in locations of cosm etic im portance such as ad jacent to the w ou nd ap p ears to be p art of the m echa-
the face. For exam p le, on the forehead , the lines of m inim al nism for m obilizing the m any cellu lar elem ents of acu te
tension are transverse, so that a transverse incision w ill tissu e rep air.
heal w ith a thinner and finer scar-line than a perpend icu lar,
vertical incision.
Follow ing gross w ou nd contam ination, second ary clo-
■ Improve nutritional status
su re (healing by second ary intent) w ill red u ce w ou nd Preoperative nu tritional repletion has been show n to
infection rates. Second ary intention occu rs in an op en, fu ll- improve surgical w ound outcomes only in cases of severe
thickness w ou nd that heals by the host biologic m echa- malnu trition (31). In fact, some stu d ies suggest that aggres-
nism s of ep ithelialization, contraction, collagen d ep osition, sive p reop erative nu tritional sup plem entation increases
and granu lation tissue form ation. Although better than w ou nd complications and surgical morbid ity and mortality,
w ou nd infection, the d raw back of this approach is that especially in oncology patients. The ad d itional proced ures
op en w ou nd s requ ire m ore nu rsing care and resu lt in a required for peripheral and enteral access as w ell as d elays
w orse cosm etic resu lt. in surgical therapy contribute to the d isappointing results of
Wound complication?
Infection? Dehiscence? Abnormal tissue?
Necrotic tissue? Foreign bodies? Ischemia? Keloid?
Hypertrophic scar?
Neoplasm?
FIGURE 13.3. Most wound complications might be clinically categorized as infections, mechanical failure (dehiscence), or abnormal
tissue (neoplasia). A systematic approach to wound complications can guide accurate diagnosis and therapy.
aggressive preoperative attempts at nutritional therapy. If be d iscu ssed in later chap ters. Wou nd d ehiscence occurs
possible, op erations should be performed w hen the seru m w hen the d istractive forces exerted p erp end icu lar to a
albumin level is 3 g. w ou nd ed ge exceed s the recovery of w ou nd m echanical
p rop erties (33).
■ DIAGNOSIS OF POSTOPERATIVE
WOUND COMPLICATIONS ■ Hypertrophic scars and keloids
A healing w ou nd shou ld rem ain stru ctu rally and fu nction- H yp ertrop hic scars are raised and often inflam ed bu t con-
ally intact and d isp lay no signs of inflam m ation. There fined to the area of the original w ou nd . Most w ill resolve
should be no intense red ness, w arm th, sw elling, or p ain slow ly over 1 to 2 years w ithou t su rgical intervention.
(ru bor, calor, tu m or, and d olor). Progressive fibrop lasia There is some evid ence that steroid d erivative injections
shou ld resu lt in a p rom inent m id w ou nd “healing rid ge”
(Fig. 13.3).
■ Wound infections
A w ou nd infection exists w hen 105 invasive organism s
per gram of w ou nd tissu e or any level of -hem olytic strep -
tococcu s are p resent. This m anifests clinically as w ou nd
cellulitis, d rainage, od or, and / or pain.
Accurate diagnosis of w ound infections requires precise
anatomical localization (Fig. 13.4). Complicated deep
w ound infections might progress to fasciitis or myonecrosis,
as in Fou rnier ’s gangrene. Surround ing skin bullae shou ld
alw ays raise concern for an invasive w ou nd infection, as
shou ld u nexp lained fevers occu rring near the fifth p ostop -
erative d ay. If the clinical presentation is confusing or if
em piric therap y fails, w ou nd biop sy for histology and
qu antitative w ound cultu res provid e the m ost d efinitive
d iagnosis of w ou nd infection. Surface w ound cu ltu res
m ight su ggest a p athogenic organism and gu id e antim icro-
bial therap y, bu t a w ound infection is not d efined until tis-
su e invasion occu rs w ith associated tissu e inflam m ation
(32).
■ Dehiscence and acute wound failure

Acu te w ou nd failure can p resent as m echanical w ound FIGURE 13.4. The accurate diagnosis and therapy of wound infections
separation or d ehiscence. Derm al w ou nd sep aration w ors- requires precise anatomical localization. Tracking of uncontrolled soft tissue
infections along fascial planes might progress to myonecrosis, as in Fournier’s
ens cosm etic results but is unlikely to cau se significant
gangrene. The development of bullae in the skin surrounding a wound should
harm . Abd om inal w all, GI, and vascular anastom osis always raise concern for an invasive wound infection. Wound tissue biopsies
w ound failu re can have life-threatening outcom es and w ill provide the most definitive diagnosis of wound infection.
(triam cinolone) can inhibit the prolonged inflamm atory ■ Antibiotics

phase of scar form ation and ind u ce rem od eling. Keloid s, in
contrast, extend beyond the bound aries of the original Antibiotic chem otherapy improves outcomes for the treat-
w ou nd and d o not regress sp ontaneou sly. Keloid s tend to ment of w ound infections. Therapeutic w ound and peri-
recu r follow ing excision, and excision alone is rarely ad e- w ou nd tissue levels are requ ired for antimicrobial efficacy.
qu ate therap y to p revent recu rren ce. Intralesion al steroid For antibiotic therapy to be successful, a w ound must first
therap y has show n benefit. Any steroid therap y m u st be ad equ ately prep ared . This most commonly means
be u sed w ith close su rveillance to avoid tissu e atrop hy d ebrid em ent of necrotic tissu e and the excision of foreign
and skin d ep igm entation. Antihistam ine therap y m ight material.
im prove the bu rning and itching often associated w ith Therap eu tic w ou nd tissu e antibiotic levels can be
keloid s and m ight help to avoid cyclical attem pts at su rgi- achieved both top ically and system ically. Often, infected
cal excision. nonhealing w ou nd s are hyp op erfu sed , lim iting the d eliv-
ery of system ically ad m inistered antibiotics. Burn eschars,
venou s stasis u lcers, and p ressu re u lcers are com m on
■ Neoplasms examp les. In these settings, top ically ap p lied antim icro-
Malignancy shou ld be consid ered in a nonhealing w ou nd bials such as silver su lfad iazine and Sulfam ylon prepara-
and a biop sy p erform ed in any op en area that is d ifficu lt to tions m ight be efficaciou s. System ically ap p lied antibiotics
d ebrid e and is failing to heal. w ill im prove w ound healing rates only if m inim um
inhibitory concentrations are reached in the w ou nd ed and
infected tissu e. Regard less of the rou te of w ou nd antibiotic
■ MANAGEMENT OF WOUND COMPLICATIONS therap y, the anti-infectives u sed w ill be m ost effective if
d irected to the organism s infecting the w ou nd . This can be
■ Wound dressings achieved by p erform ing qu antitative w ou nd cu ltu res. In
Most w ou nd com p lications can be m anaged nonop era- general, first-generation penicillins and cephalosporins
tively. Ap p rop riately d ressing and protecting a w ou nd can p rovid e a spectru m of coverage for most Gram-positive
red u ce the incid ence of w ound com p lications. Basic skin su rface organism s, w hile second -generation and third -
w ou nd healing stu d ies and clinical research have con- generation cephalosporins and mod ified , later-generation
firmed that w ou nd healing is optim ized in a m oist environ- p enicillins increase Gram-negative and enteric coverage at
ment (34). The id eal w ou nd d ressing therefore shou ld the exp ense of anti–Gram -positive activity.
protect a w ou nd against d esiccation (hyd rophobic d ress-
ing). In ad d ition, d ressings shou ld keep a w ou nd clean,
■ Wound adjuvants
protect against rep eated w ound trau ma, absorb exu d ates,
and m inim ize w ou nd pain (Fig. 13.5). The high prevalence of nonhealing w ound s has stim ulated
Sp ecific typ es of w ou nd s have u niqu e requ irem ents for the d evelopm ent of novel ad ju vants d esigned to im prove
optim ized tissu e rep air. Pressu re u lcers need off-load ing to w ou nd -healing ou tcomes. Vacu um-assisted w ound closu re
im prove cap illary p erfusion of the w ound and su rround - can improve closure rates. The m ost common d esign allow s
ing skin and to m inim ize trau matic shear forces. Venou s maintenance of a moist w ound environment, d rainage of
stasis u lcers heal best w hen low er extrem ity sequ ential w ou nd exu d ates, and continuous negative p ressure to the
com p ression is u sed , in part, to im prove cap illary p erfu - open w ou nd surface. This arrangement has been show n to
sion and tissu e oxygen d elivery (35). accelerate the appearance of repair fibroblasts in the w ound
Management of wound complications FIGURE 13.5. The management of

wound complications may apply
nonoperative and operative princi-
ples. The optimum dressing protects
Medical Surgical
the wound from repeat trauma and
maintains a moist wound environ-
ment. Topical antibiotic therapy might
Appropriate dressing? Antibiotics? Nutrition? Debridement? be effective when the infection is
confined to the wound, especially
when wound blood supply is compro-
Wound moist? Topical? mised. Surgical therapy is fundamen-
tal to the successful management of
complicated wounds.
Exudates controlled? Systemic?
Protect wound?
and to improve w ound perfu sion (36). H BO therapy has Strictu re p lasties of GI strictu res ap p ly the sam e p rincip les
also been show n to imp rove the healing rates of d ifficult in an effort to red irect scar forces.
w ound s. When transcutaneous tissue oxygen levels of 30
mm H g are achieved , reported w ound closure rates have
been accelerated by 50% (21). ■ REFERENCE
1. Robson MC, Steed DL, Franz MG. Wou nd healing: biologic featu res
and app roaches to m axim ize healing trajectories. Curr Probl Surg 2001;
■ Debridement 38(2):77–89.
2. H enry G, Garner WL. Inflam m atory m ed iators in w ou nd healing. Surg
A skin w ound should be reopened w hen w ound infection is Clin North Am 2003;83:491–497.
suspected or if surround ing cellulitis d oes not respond to 3. Clark RAF. The molecular and cellular biology of wound repair, 2nd ed .
N ew York: Plenu m Pu blishing; 1995.
antibiotics. This allow s a quantitative wound culture to be 4. Robson MC, H ill DP, Wood ske ME, et al. Wou nd healing trajectories as
performed for more accurate diagnosis. In add ition, an open p red ictors of effectiveness of therap eu tic agents. Arch Surg 2000;135:
w ound can be d ebrid ed w ith moist gauze d ressing changes 773–777.
5. Fergu son MW, Whitby DJ, Shah M, et al. Scar form ation: the sp ectral
several times a d ay. Dressing d ebrid em ent low ers w ound nature of fetal and ad ult w ou nd rep air. Plast Reconstr Surg 1996;97:
bacterial counts directly and by removing from the w ound 854–860.
necrotic tissue that acts as a nutrient supply for invasive 6. Tzeng E, Billiar TR. N itric oxid e and the su rgical p atient: id entifying
therap eutic targets. Arch Surg 1997;132:977–982.
organisms. 7. Yam asaki K, Ed ington H D, McClosky C, et al. Reversal of im p aired
N ecrotic w ou nd s m ight need m ore aggressive surgical w ou nd repair in iN OS-d eficient m ice by topical ad enoviral-m ed iated
intervention. N ecrotic w ound tissu e is by d efinition w ith- iN OS gene transfer. J Clin Invest 1998;101: 967–971.
8. Leibovich SJ, Polverini PJ, Fong TW, et al. Prod u ction of angiogenic
out a blood su p p ly and w ill not heal. N ecrotic tissue shou ld activity by hu m an m onocytes requires an L-arginine/ nitric oxid e syn-
therefore alw ays be d ebrid ed from w ou nd s. The m ost reli- thase-d ep end ent effector m echanism . Proc Natl Acad Sci USA 1994;91:
able w ay to d ebrid e any w ou nd is sharply using stand ard 4190–4194.
9. Rap polee DA, Mark D, Band a MJ, et al. Wou nd m acrop hages exp ress
surgical p rincip les. N ecrotic tissue should be excised back and other grow th-factors in vivo: analysis by m RN A p henotyp ing. Sci-
to healthy ap p earing soft tissu e w ith obviou s blood su p p ly. ence 1988;241:708–712.
All foreign m aterial-like asphalt or retained sutures should 10. Paju lo OT, Pu lkki KJ, Lertola KK, et al. H yalu ronic acid in incision
w ou nd fluid : a clinical stu d y w ith the Cellstick d evice in child ren.
also be d ebrid ed from a nonhealing w ou nd . Debrid em ent Wound Repair Regen 2001;9(3):200–204.
might be lim ited by extension to a nonhealing su rface or 11. Gosiew ska A, Yi CF, Brow n LJ, et al. Differential exp ression and regu la-
stru ctu re su ch as tend on sheath or bone. In these cases, a tion of extracellular m atrix-associated genes in fetal and neonatal
fibroblasts. Wound Repair Regen 2001;9(3):213–222.
viable tissu e transfer m ight be ind icated . Chem ical enzy- 12. Morgan CJ, Pled ger WJ. Fibroblast p roliferation. In: Cohen IH , Diegel-
matic w ound d ebrid em ent is efficacious w hen surgical m ann RF, Lind blad WJ, ed s. Wound healing: biochemical and clinical
d ebrid em ent is not available, bu t it rem ains a second -line aspects. Philad elphia, PA: WB Sau nd ers; 1992:63–76.
13. Ballas CB, Davison JM. Delayed w ou nd healing in aged rats is associ-
alternative to com p lete su rgical excision. Protease com - ated w ith increased collagen gel rem od eling and contraction by skin
pou nd s of p ap ain and collagenases are often ap p lied . fibroblasts, not w ith d ifferences in ap op totic or m yofibroblast cell p op -
Chem ical d ebrid em ent is effective only for the rem oval of u lations. Wound Repair Regen 2001;9(3): 223–237.
14. Prockop DJ, Kivirikko KI, Tu d erm an L, et al. The biosynthesis of colla-
necrotic soft tissu e and biofilm s. Enzym atic treatm ent can- gen and its d isord ers. N Engl J Med 1979;301:13–23.
not rep lace surgical d ebrid em ent of com plicating foreign 15. Jorgensen LN , Kellehave F, Karlsm ark T, et al. Red u ced collagen accu -
materials. m ulation after m ajor su rgery. Br J Surg 1996;83:1591–1594.
16. Robson MC, Mustoe TA, H u nt TK. The fu tu re of recom binant grow th
Serom as and hem atom as can im p ed e w ou nd healing. factors in w ou nd healing. Am J Surg 1998;176 (Su p p l 2A): 80–82.
These flu id collections m echanically d istract w ou nd ed ges 17. Fried m an DW, Boyd CD, N orton P, et al. Increases in typ e III collagen
and red u ce cap illary perfu sion. Wound fluid collections gene exp ression and p rotein synthesis in p atients w ith ingu inal her-
nias. Ann Surg 1993;218:754–760.
also increase the risk of w ou nd infection. Whenever p ossi- 18. Culver DH. Surgical wound infection rates by wound class, operative
ble, w ou nd serom as or hem atomas that are not sp onta- proced ure and patient risk index. Am J Med 1991;91(Suppl 3B):152–157S.
neously resolving or that are associated w ith a w ou nd 19. H oran TC, Gaynes RP, Martone WJ, et al. CDC d efinitions of nosoco-
m ial su rgical site infections, 1992: a m od ification of CDC d efinitions of
com plication like infection or d ehiscence shou ld be aspi- su rgical w ou nd infections. Am J Infect Control 1992;20:271–274.
rated or d rained through the open incision. If the w ou nd 20. Best WR, Khu ri SF, Ph elan M, et al. Id en tifyin g p atient p reop erative
fluid collection is associated w ith a nearby im planted risk factors and p ostop erative ad verse even ts in ad m in istrative d ata-
bases: resu lts from the Dep artm ent of Veteran s Affairs N ational
d evice, it m ight be best to attem pt need le aspiration of the Su rgical Qu ality Im provem ent Program . J Am Coll Surg 2002;194(3):
fluid collection u nd er sterile cond itions to m inimize the 257–266.
risk of a foreign bod y infection. 21. H u nt TK. Physiology in w ou nd healing. In: Clow es GH A, ed . Trauma,
sepsis and shock: the physiological basis of therapy. N ew York: Marcel
Dekker Inc; 1988:443–471.
22. Dem ling RH , DeSanti L. The stress resp onse to inju ry and infection: the
■ Scar revision role of nu tritional su p port. Wounds 2000;12:3.
23. Leap er DJ, Gottru p F. Su rgical w ou nd s. In: Leap er DJ, H ard ing KG,
Scars resu lting in p oor cosm etic resu lts can be su rgically ed s. Wounds: biology and management. Oxford : Oxford University Press;
revised . The broad goal of scar revision is to reorient the 1998:23–40.
scar into lines of tension so that the d im ension of the scar 24. Gibbons GW. Low er extrem ity byp ass in p atients w ith d iabetic foot
u lcers. Surg Clin North Am 2003;83:659–669.
is oriented into lines of relaxation. The techniqu es m ost 25. Carlson MA. Acu te w ou nd failu re. Wou nd healing. Surg Clin North Am
often u sed for d erm al scars are Z-p lasties or W-p lasties. 2001;77(3):607–635.
26. Folli S, Morgagni P, Bazzocchi F, et al. An alternative rep air techniqu e 31. William s JG, Barbu l A. N u trition and w ou nd healing. Surg Clin North
for anastom otic leakage after total gastrectom y. J Am Coll Surg Am 2003;83:571–596.
2000;190(6):757–759. 32. Robson MC, Shaw RC, H eggers JP. The reclosu re of p ostop erative inci-
27. Vignali A, Fazio WV, Lavery I, et al. Factors associated w ith the occu r- sional abscesses based on bacterial qu antification of the w ou nd . Ann
rence of leaks in stap led rectal anastom osis: review of 1,014 cases. J Am Surg 1970;171:279.
Coll Surg 1997;185:105–113. 33. Du Bay DA, Franz MG. Acu te w ou nd healing: the biology of acu te
28. Irvin TT, H u nt TK. Pathogenesis and p revention of d isrup tion of w ou nd failu re. Surg Clin North Am 2003;83:463–481.
colonic anastom oses in trau m atized rats. Br J Surg 1974;61: 437–439. 34. Bolton L, Pirone L, Chen J. Dressings’ effects on w ou nd healing.
29. Tad ros T, Wobbes T, H end riks T. Blood transfu sion im p airs the heal- Wounds 1990;2:126–134.
ing of exp erim ental intestinal anastom oses. Ann Surg 1992;215: 35. Macd onald JM, Sim s N , Mayrovitz H N . Lym p hed em a, lip ed em a and
276–281. the op en w ound : the role of com p ression therap y. Surg Clin North Am
30. Tani T, Tsu tam oto Y, Egu chi Y, et al. Protease inhibitor red uces loss of 2003;83:639–658.
tensile strength in rat anastom osis w ith p eritonitis. J Surg Res 2000;88: 36. Lionelli GT, Law rence WT. Wou nd d ressings. Surg Clin North Am 2003;
135–141. 83:631–633.
CHAPTER
14
Surgical Site Infections

Gerard M. Doherty
Surgical site infections (SSIs) are a potential complication of fascia and m u scle of the abd om inal w all. Organ space
all operative interventions. To minimize the risk of SSI for infections involve either the solid or hollow organs them -
any proced u re, the surgeon mu st und erstand the risk of selves or the p otential sp aces su rrou nd ing them . Exam ples
infection, and the available interventions for p reventing this of this inclu d e intrap eritoneal abscess, hep atic abscess, or
complication, as w ell as the management options available retrop eritoneal abscess. The u se of these d escriptors to
if one d oes occu r. The prevention m ethod s includ e optim iz- characterize SSIs is m and ated by the CDC in its N ational
ing the patient’s health and tissu e p erfu sion preoperatively H ealthcare Safety N etw ork (N H SN ) system , w hich has
and p ostop eratively, m inim izing w ou nd contam ination by rep laced the p reviou s N ational N osocom ial Infections Su r-
carefu l sterile techniqu es, avoid ing resid u al d evitalized veillance (N N IS) system by com bining N N IS w ith other
tissues by careful operative technique, and , finally, ad minis- efforts to inclu d e all healthcare associated infections (1).
tering prophylactic antimicrobials appropriate to the infec- This effort, throu gh its legacy p rojects, has been u sed since
tious risk, in the most ad vantageous d oses and timing. 1970 to rep ort trend s in nosocom ial infections in U.S. acute
Treatm en t m eth od s in clu d e d rain age of infected flu id care hosp itals. These d efinitions m u st be carefu lly ad hered
collections, removal of d evitalized tissue, elimination of to in ord er to p rovid e interp retable and com p arable resu lts.
sources of contamination, and ad ministration of appropri-
ately selected antibiotics. Contamination
The risk for SSIs can also be characterized based on the
■ CLASSIFICATION AND RISK OF extent of contamination of the proced ure (4). The d escriptive
surgical w ound classification scheme (Table 14.1) is used to
SURGICAL SITE INFECTION
help characterize the inoculum of infectious agent that
■ Classifications affects the risk of a patient d eveloping infection. Wound s are
classified along a spectrum from clean to dirty or infected
The consistent d iscu ssion of SSIs requ ires stand ard ized
w ounds. The risk of w ound infection increases as the level of
d efinitions for both the p resence of infection and the risk of
bacterial contamination of the w ound increases.
infection. Only w ith the d efinition of these tw o issu es can
the actu al institu tional occu rrence of an infection be ration-
ally interp reted . SSIs are com m only d iscussed and classi- ■ Risk of infection
fied accord ing to their site and the level of contam ination
associated w ith the p roced ure. For a su rgical infection to occu r, there m u st be m icrobial
contam ination of the su rgical site. H ow ever, not all m icro-
Sites bial contam ination resu lts in SSI, and the sam e bacterial
The Centers for Disease Control (CDC) has d evelop ed stan- inocu lu m d oes not alw ays resu lt in SSI. There are a variety
d ard ized su rveillance criteria for d efining SSIs (1–3). Und er of m od ifying featu res in ad d ition to the d ose and virulence
these criteria, SSIs are d efined as being either incisional or of the w ou nd contam inates (Fig. 14.2).
organ sp ace. The incisional infections are fu rther d ivid ed Featu res of the bacteria that can affect the occurrence of
into either superficial incisional or d eep incisional SSIs SSI inclu d e the d ose of the bacterial inocu lu m. If a su rgical
(Fig. 14.1). Su p erficial incisional site infections includ e only site is contam inated w ith greater than 100,000 microorgan-
the skin and su bcu taneou s tissu es. This is the m ost com - ism s p er gram of tissu e, then the risk of SSI is high (5,6).
mon typ e of w ou nd infection. Less com m on, and also often H ow ever, the d ose of m icroorganism s can be m u ch low er if
requ iring m ore invasive m anagem ent, are d eep incisional the bacteria contain or prod u ce toxins that increase their
SSIs. These infections involve the d eep soft tissu e su ch as ability to invad e a host, p rod u ce d am age w ithin the host, or
su rvive in the host tissu e (7,8). Some bacterial su rfaces
inhibit p hagocytosis, p articu larly by exp ressing a polysac-
Gerard M. Doherty: University of Michigan, Ann Arbor, charide capsule, w hich limit an important early host defense
MI 48109-5331 system. Other bacteria may produce potent exotoxins that
140
Chapter 14 • Surgical Site Infections 141
FIGURE 14.1. Surgical site infection depth classification: The classifica-

tion of surgical site infection based on the deepest extent of the infection.
Superficial incisional infections involve only the skin and subcutaneous tis-
sues. Extension into the fascia or muscular layers of the body wall is deep
incisional wound infection. Involvement of the solid or hollow viscous organs
or the surrounding potential spaces inside the body wall is organ/space
infections.
FIGURE 14.2. Factors affecting the development of surgical site infections.

d isru p t cell m em branes or intracellu lar m etabolism , and A variety of hosts, contaminating organisms, and treatment factors affect the
can thu s invad e tissu es and lim it an effective host resp onse. development of surgical site infection (SSI).
Still other bacterial species prod uce a glycocalyx and asso-
ciated extracellu lar com p onent (slim e) w hich p hysically
shield s the bacteria from the host im mu ne system and host im m u ne system ability to resp ond to w ou nd contam i-
inhibits the bind ing and p enetration of antim icrobial nants (4).
d ru gs. Each of these factors specific to the bacteria can The goal of u nd erstand ing the relationship betw een the
m od ify the d ose necessary for a w ou nd contam inant to d ose of w ou nd contam inants, the p resence of d evitalized
p rod uce a SSI. tissu e or foreign bod ies, and the host resistance to infection,
Other featu res of the w ou nd and the host can p rod u ce a is to be able to m od ify each of these factors to lim it the
relative resistance or lack of resistance to SSI. In p articu lar, occu rrence of SSI (6). Efforts to elim inate or d im inish the
the presence of d evitalized tissue or foreign bod y w ithin a w ou nd contam ination inclu d e skin p rep aration, bow el
contam inated w ou nd can increase the risk of infection by p rep aration, and incision care for the p atient. This is also
lim iting the ability of the host resp onses to clear the bacter- the m otivation for op erating room cleanliness and sterile
ial inocu lu m . In ad d ition, the status of the host im m u ne techniqu e. Op erative techniqu e, op erative strategy choices
system can change the host resistance to infection (9,10). If regard ing foreign bod y u se, and the em p loym ent of
the native im m une system is supp ressed by m ed ications, laparoscopy can alter the presence of d evitalized tissu e or
chronic illness, hyperglycem ia, or nutritional d eficiency, foreign bod ies w ithin the w ou nd , and m ay thu s limit the
then a sm aller d ose of bacterial contam ination m ay still risk of SSI. Finally, carefu l attention to the host resistance to
p rod u ce an infection. Alternatively, the ad d ition of antibi- infection and the approp riate u se of antim icrobial prophy-
otic agents to the w ou nd environm ent m ay enhance the lactic d ru gs m ay alter this com ponent of the SSI balance.
Table 1 4 .1 Su r gica l wou n d cla ss

Class Description
Clean Uninfected operative wound without inflammation or entry into the respiratory, alimentary, genital, or urinary tracts.
Clean-contaminated Uninfected operative wound through which the respiratory, alimentary, genital, or urinary tracts are entered in a controlled fashion
without unusual contamination. Specific examples include operations on the biliary tree, appendix, vagina, and oropharynx, if no un-
usual contamination or evidence of gross infection occurs.
Contaminated Operations with major breaks in sterile technique, gross spillage from the alimentary tract, or acute, nonpurulent inflammation. Also
includes open, fresh traumatic wounds
Dirty/infected Operations into fields that are contaminated by existing clinical infection or alimentary contents from perforated viscus. Also in-
cludes traumatic wounds that are older and contain retained devitalized tissue.
Thus, the carefu l consid eration of these issues is im p ortant investigated fu rther, as it m ay ind icate som e sp ecific or
to m inim izing the risk of this com p lication. system ic p roblem w ithin the institu tion that is creating a
d iscrep ancy. Sim ilarly, a rate su bstantially low er than the
national benchm ark d ata m ay ind icate either an excep-
■ National healthcare safety network tional level of p ractice or a failu re to d etect infections by the
The N H SN (http :/ / w w w.cd c.gov/ nhsn/ ) w as d evelop ed su rveillance p rogram that is in p lace. The institution of
in 2005 to com bine the w ork of three legacy efforts: the som e hosp ital infection control p rogram to d efine these
N N IS, the Dialysis Su rveillance N etw ork, and the N ational rates, su ch as the N H SN system , is an im p ortant com po-
Su rveillance System for H ealthcare Workers. The N N IS nent of qu ality system s-based patient care.
w as established in 1970 in selected hospitals w ithin the
United States (11). These hospitals began rou tinely rep ort- ■ Microbiology of surgical site infection
ing their nosocom ial infection su rveillance d ata to a
national d atabase that is now reported as N H SN d ata (1). The m icrobiology of SSIs has not changed significantly
Greater than 1500 acute care ad u lt or child ren’s hosp itals d u ring the last d ecad e (1,4,12). The m ost com m only iso-
particip ate; their id entities are confid ential. The N H SN lated p athogens inclu d e Staphylococcus aureus, coagulase
d ata are collected accord ing to stand ard ized protocols, and negative staphylococci, enterococcus species, and Escherichia
includ e separate com ponents for ad u lt and ped iatric inten- coli. However, there has been an increasing incidence of SSIs
sive care u nit infection rates, high-risk nursery infection caused by antibiotic resistance pathogens, such as methicillin-
rates, and su rgical infection rates. The SSI statistics are resistant S. aureus (MRSA) (6,12). This increased proportion of
mainly contained w ithin this third com p onent. SSIs caused by resistant pathogens may be due to the
The N H SN su rgical p atient su rveillance d ata are cate- increased and widespread use of broad spectrum antibiotics.
gorized accord ing to the proced ures perform ed . Record s Most SSIs are cau sed by p athogens that are id entified
for every patient includ e inform ation on risk factors su ch on the skin of the p atient (Table 14.3). Thu s m ost operations
as w ou nd class, d u ration of op eration, Am erican Society of can be com p licated by infection w ith S. aureus or coagu -
Anesthesiologists (ASA) score, inpatient or ou tpatient sta- lase-negative stap hylococci. H ow ever, a violation of the
tu s, and the u se of lap aroscopy or end oscopy to perform respiratory or gastrointestinal tract or other sites that are
the proced u re. These d ata are then com bined to create risk colonized w ith bacteria, m ay lead to infection w ith specific
ind ex categories. The risk ind ex category is calculated by organism s. Exam p les of this inclu d e gram -negative bacilli
counting the nu mber of risk factors that the p atient has. anaerobic bacteria or enterococci that m ay comp licate oper-
The risk factors are an ASA score greater than or equ al to 3, ations on the gastrointestinal tract. Op erations that traverse
a d u ration of op eration greater than the 75th percentile for the oropharyngeal m u cosa m ay contam inate the w ou nd
that p roced u re, or a w ound class of contam inated or d irty. w ith orop haryngeal anaerobic bacteria, w hich can cause
There are nom inally four risk ind ex categories for SSIs, rep - infections in these w ou nd s.
resenting p atients w ho have 0, 1, 2, or 3 of the risk factors. Know led ge of the sp ecific p athogen that is likely to
H ow ever, if tw o risk ind ex categories are sim ilar, then cau se SSIs is necessary to ap p rop riately select p rop hylactic
those tw o categories are com bined into a single category antim icrobial therap y for those p atients at risk.
(Table 14.2). For exam ple, in Table 14.2, w hile there are fou r
separate risk categories for colon operations, in the chole- ■ Specific risk factors
cystectom y category there are only three reported risk
ind ex categories, as 2 and 3 are com bined into 2,3. For other Effect of Laparoscopy on Risk
d ata sets, there w ere insu fficient patients w ithin som e cate- One of the im portant featu res in the risk of SSI is the u se of
gories to p erform statistical analysis, and so those risk lap aroscop y to p erform the p roced u re (4,11). Lap aroscopy
ind ex categories are not rep orted . m ay be exp ected to d ecrease the risk of SSI becau se of
Table 14.2 show s som e of the N H SN d ata for the d ecreased tissu e trau m a, d ecreased d ead sp ace in the su b-
2006–2008 p eriod regard ing m ean infection rate p er 100 cu taneou s tissu e that m ight p rovid e a site for su rgical
proced u res for all hospitals (1). The d ata are then sep arated infection, and m ore lim ited tissu e trau m a overall. The
by percentile of hospitals to d em onstrate the spread in occu rrence of SSI is significantly d ecreased by the u se of the
infection rate across institutions. More d etailed d ata are lap aroscop e to d o sim ilar p roced u res. This ad vantage m ay
available in the reference. These d ata provid e very reliable be offset if the laparoscopic proced u re takes significantly
and w ell-d efined inform ation regard ing SSI rates for com - longer ( 75th p ercentile for that p roced u re). In general, the
monly p erform ed p roced u res across the United States. This d ecreased tissu e trau m a for lap aroscop y ap p ears to have a
allow s benchm arking and com parison of hospital infection beneficial effect on the SSI risk.
rates. H osp ital infection rates can be com pared to these
only if the d ata is collected com p letely and in accord ance Tobacco use
w ith the CDC d efinitions. If these d efinitions are follow ed , The use of tobacco m ay increase the risk of SSI by d elaying
then the d em onstration of a high rate of infection for som e p rim ary w ou nd healing (13–15). This has been clearly
proced u re m ay help to id entify an area that shou ld be d em onstrated for sternal or m ed iastinal SSIs after card iac
Table 1 4 .2 Percen t ile d ist r ibu t ion s of h osp it a l r isk of su r gica l sit e in fect ion (SSI) by p roced u r e
a n d N H SN r isk in d ex
NNIS Duration
Risk Cutpoint No. of Mean Mean Rate for percentile of Hospitals
Procedure Index (Minutes) Hospitals Rate a 10% 25% 50% 75% 90%
Cardiac 0, 1 306 150 1.10 0 0 0.49 1.64 2.60
Cardiac 2, 3 145 1.84 0 0 1.24 3.25 4.71
CABGb 0 301 135 0.35
CABGb 1 292 2.55 0 0.65 1.90 3.45 5.37
CABGb 2 285 4.26 0 1.33 3.08 5.81 8.70
CABG 3 48 8.49
Thoracic 0, 1 188 15 0.76
Thoracic 2, 3 14 2.04
Appendectomy 0, 1 81 31 1.15 0 0 0.60 1.23 2.76
Appendectomy 2, 3 27 3.47
Cholecystectomy 0 99 96 0.23 0 0 0 0 0.86
Cholecystectomy 1 95 0.61 0 0 0 0.97 2.06
Cholecystectomy 2, 3 92 1.72 0 0 0 3.23 4.73
Cholecystectomy 0 65 71 0.11 0 0 0 0 0.13
(Outpatient)
Cholecystectomy 1, 2, 3 71 0.34 0 0 0 0 0.47
(Outpatient)
Colon 0 187 278 3.99 0 1.58 3.49 5.56 8.73
Colon 1 292 5.59 0 2.06 4.48 7.43 11.16
Colon 2 277 7.06 0 2.38 5.06 9.09 13.78
Colon 3 207 9.47
Gastric 0, 1 160 40 1.72 0 0.70 1.21 2.57 3.58
Gastric 2, 3 37 4.23 0 1.04 2.30 5.00 8.16
Small bowel 0 192 29 3.44
Small bowel 1, 2, 3 32 6.75
Herniorrhaphy 0 124 89 0.74 0 0 0 1.77 2.42
Herniorrhaphy 1 88 2.32 0 0 1.02 3.15 5.63
Herniorrhaphy 2.3 72 5.25
Thyroid/Parathyroid 0, 1, 2, 3 150 11 0.26
Splenectomy 0, 1, 2, 3 217 15 2.33
Exploratory 0, 1 199 29 1.67 0 0 0 1.08 1.91
Laparotomy
Exploratory 2, 3 21 2.82 0 0.78 1.54 2.54 3.79
Laparotomy
a
Per 100 procedures.
b
Coronary artery bypass graft, includes vein harvest site.
Table 1 4 .3 Lik ely su r gica l sit e in fect ion p a t h ogen s a n d p rop hyla ct ic a n t ibiot ic op t ion s
Antibiotic Prophylaxis a,b
Procedure Site Pathogen First Choice Second Choice
Breast Staphylococcus aureus Cefazolin 1 g IV, single dose Clindamycin 600 mg IVor
Abdominal wall hernia Coagulase-negative staphylococcus Vancomycin 1 g IV
Vascular
Placement of grafts, prostheses or
other foreign material
Noncardiac thoracic S. aureus Cefazolin 1 g IV, single dose Clindamycin 600 mg IVor
Coagulase-negative staphylococcus Vancomycin 1 g IV
Streptococcus pneumoniae
Gram-negative bacilli
Biliary tractc S. aureus Cefotetan 1 g IV, single dose Clindamycin 600 mg and
Pancreas Gram-negative bacilli Or Gentamicin 2 mg/kg IV
Small bowel Anaerobes Ampicillin/sulbactam 1.5 g IV
Appendix Enterococci
Colon and rectumd
Liver transplant S. aureus Ampicillin/sulbactam 3 g IV; then Levofloxacin 500 mg IV
Gram-negative bacilli 1.5 g every 3 hours intra-operatively
Anaerobes
Enterococci
Kidney transplant S. aureus Cefazolin 1 g, single dose Levofloxacin 500 mg IV
Coagulase-negative staphylococcus
Gram-negative bacilli
Anaerobes
Enterococci
Esophagus S. aureus Cefazolin 1 g, single dose Clindamycin 600 mg IVor
Stomach Gram-negative bacilli Vancomycin 1 g IV
Duodenum Streptococci
Oropharyngeal anaerobes
(peptostreptococci)
Head and neck (with entry through S. aureus Cefazolin 1 g, single dose Clindamycin 600 mg and
oropharyngeal mucosa) Streptococci Or Gentamicin 2 mg/kg IV
Oropharyngeal anaerobes Ampicillin/sulbactam 1.5 g IV
(peptostreptococci)
a
Prophylactic antibiotics should be administered within 60 minutes before incision. Antibiotic infusions (vancomycin or fluoroquinolones) should be completed within
60 minutes of incision.
b
For most procedures, a single dose of antibiotics is adequate. One additional intra-operative dose should be given after 3 hours, if the operative procedure requires more than
3 hours.
c
Laparoscopic cholecystectomy has a lower incidence of SSI than open procedures, and antibiotic prophylaxis is not necessary.
d
Mechanical and antibiotic bowel preparation prior to operation; the mechanical portion of the preparation is controversial and may be omitted (see text). Oral neomycin
sulfate 1 g and erythromycin base 1 g is given after the mechanical preparation is complete at 19, 18, and 9 hours prior to operation.
Compiled from Mangram AJ, Horan TC, Pearson ML, et al. Guideline for prevention of surgical site infection, 1999. Am J Infect Control 1999;27:97–134. University of
Michigan Pharmacy and Therapeutics Committee, Antimicrobial Subcommittee Guidelines.
surgery. It is not know n w hether short-term sm oking cessa- the presence of d iabetes w ith SSI risk (9). It is not clear that
tion alters this risk. tighter perioperative glucose control w ill alter the risk of
SSI, although d ata regard ing phagocytic properties of the
Diabetes host im m u ne system w ould suggest that hyperglycem ia
The contribution of d iabetes to SSI risk is controversial only im pairs this im portant early host d efense m echanism .
because there are often other confound ing variables in d ia-
betic patients und ergoing op erations. These may inclu d e Steroid use
the presence of vascular d isease and obesity. H ow ever, Patients receiving steroid s or other im m u nosu ppressive
there are d ata that suggest a relationship betw een increas- d ru gs are p red isp osed to d evelop ing SSI (10). Patients w ho
ing levels of hem oglobin A1C, increased glucose levels, and are on long-term steroid s for Crohn’s d isease or chronic
im m u nosu p p ression follow ing solid organ transp lantation recent m eta-analyses of the available rand om ized clinical
have a higher risk of SSI (16). There is limited opp ortu nity trials each fail to su p p ort the hyp othesis that m echanical
to alter this p ost-transp lantation im m u nosu p p ression in bow el p rep aration d ecreases infectiou s com plications
patients w here im m u nosu ppression is necessary. H ow ever, (20–22). In fact, they each show that the risk of anastom otic
recognition of the increased risk m ay allow increased atten- leakage is significantly increased after mechanical bow el
tion to other factors p red isp osing or p rotecting from SSI. p rep aration for elective colon or rectal op erations. The
stand ard bow el p rep aration w ith antibiotics inclu d es
neom ycin and erythrom ycin base d elivered p rior to opera-
■ PREVENTION OF SURGICAL SITE INFECTION
tion (Table 14.3). In contrast to the m echanical preparation,
The p revention, or m inim ization of risk, of SSI requ ires the u se of oral antibiotics p lu s intravenou s antibiotics has
know led ge of all of the risk factors for infection and the been consistently su p erior to intravenou s antibiotics alone,
mod ification of each of these as is p ossible. Althou gh d is- in both ind ivid ual rand om ized trials and m eta-analysis of
cu ssion of the p revention of SSI is often focu sed on antim i- the available d ata (23,24). In ad d ition, p atients shou ld have
crobial p rop hylaxis tim ing and choices, there are other ad equ ate tissu e levels of effective antim icrobial agents
im portant factors that m ust be consid ered . d elivered intravenou sly in the stand ard p rop hylactic regi-
m en, as the tissu e levels correlate w ith the risk of SSI (23).
■ Tissue oxygenation
Prosp ective d ata have d em onstrated that d ecreased tissu e
■ Treat remote infections
oxygenation is associated w ith increased risk of SSI. This Patients w ith infections remote from the site of planned
effect is explainable based on the need for oxygen rad ical operation shou ld have these treated preop eratively. Most
prod u ction in the early p hases of host d efense against bac- infections result in some circulating microbial load and
teria contam inants. There are a variety of periop erative som e im m une im pairm ent of the patient. The creation of a
issues that can affect the level of tissu e oxygenation. new operative w ound w ith its d evitalized tissue and poten-
H yp otherm ia triggers peripheral vasoconstriction w hich tial foreign bod y creates another site w here this infection
d ecreases tissu e oxygenation. In ad d ition, relative d ehy- may be harbored . Thus it is important and generally recom-
d ration, and p ain w ith perip heral vasoconstriction also mend ed that remote sites of infection be ad equately treated
contribu te to d ecreased tissu e oxygenation. Thu s to op ti- or at least treatment begu n p rior to creating new w ou nd s.
mize p eripheral tissue oxygenation and to try to minim ize
the risk of SSI, ad equate pain control, ad equ ate or su p er-
ad equ ate intravascu lar hyd ration, and m aintenance of nor-
■ Skin preparation
mal bod y tem p eratu re are all im portant, as is ad equ ate Skin preparation is perform ed to try and d ecrease the bac-
sup p lem ental oxygen d elivery. Resuscitation w ith colloid terial w ou nd contam inant at the tim e of op eration. The
may be as effective as resuscitation w ith crystalloid solu- p reparation of the skin involves several steps w hich m ay
tions for the m aintenance of intravascu lar volu m e and each contribu te to an op tim al ou tcom e.
perip heral tissu e oxygenation. Delivery of su p p lem ental
oxygen also d ecreases the incid ence of w ound infection. In Preoperative Shower
a p rosp ective rand om ized trial, colorectal su rgery p atients A preoperative antisep tic show er or bath can d ecrease skin
w ho received su p p lem ental oxygen (FIO 2 0.8) had a m icrobial cou nts. H ow ever, in sp ite of the d em onstration of
low er infection rate than those w ho d id not (FIO 2 0.3), the d ecrease in skin m icrobial cou nts and trend s tow ard
w ith actu al rates of 5.2% and 11.2%, respectively (17). This d ecreased SSI rates, p reop erative show ers d o not d efini-
w as correlated w ith an increased su bcu taneou s tissue oxy- tively red u ce SSI rates (25,26). Gross contam ination of the
gen p artial p ressu re. In ad d ition, su pplem ental crystalloid skin shou ld be cleansed prior to bringing the patient into
to m aintain high intravascu lar volum e, and presum ably the operating room environm ent.
perfu sion (16–18 m L/ kg/ h) increased the su bcu taneou s
tissu e oxygen p artial pressu re. Tissue oxygenation w as also Hair Removal
im p roved in patients rand om ly assigned to more aggres- Rem oval of hair from the su rgical site is controversial. It
sive control of p ostoperative pain (18,19). has been habit in the United States to rem ove the hair from
the su rgical site prior to operation because of concern
abou t contam ination. H ow ever, stu d ies have d em on-
■ Bowel preparation strated that removal of the hair by shaving the night before
For operations that w ill open the colon through the op eration is associated w ith a higher risk of infection than
mu cosa, mechanical preparation of the bow el and alter- shaving or clip p ing the hair im m ed iately p rior to the oper-
ation of its flora w ith oral antibiotics have been u sed for ation (27). In ad d ition, d ep ilatories ap p ear to have a low er
many years to try to d ecrease the risk of SSI. The u tility of infection rate than shaving or clip p ing, bu t have som e sig-
mechanical preparation of the bow el in association w ith nificant hyp ersensitivity reaction rate (28). Som e stu d ies
the red u ction of intralum inal bow el flora is not clear. Three d em onstrate that p reop erative hair rem oval by any m eans
has a higher risk of infection than no hair rem oval at all. It Room Surfaces
is clear that if the hair is to be rem oved , it shou ld be clip p ed The surfaces in the operating room (includ ing tables,
in as atrau m atic a fashion as possible im m ed iately prior to floors, w alls, ceilings, and lights) m u st be cleansed rou-
the op eration (28–31). Alternatively, rem oving no hair at all tinely to re-establish a clean environm ent for each opera-
appears accep table (32). tion (4). There are no d ata to su p p ort rou tine d isinfection of
Operating Room Skin Preparation these su rfaces betw een operation in the absence of gross
contam ination or visible soiling. If su ch contam ination
The p rep aration of the skin in the op erating room is d oes occu r, then a d isinfectant agent shou ld be u sed prior
d esigned to rem ove as m uch of the bacterial load as p ossi- to the next op eration (36). Wet vacu u m ing of the floor w ith
ble from the op erative site prior to incision (4). The skin a hosp ital d isinfectant shou ld be p erform ed rou tinely after
shou ld be free of gross contam ination p rior to the initiation the last op eration of the d ay or night. There are no d ata to
of the skin p rep aration. The antiseptic is applied in concen- supp ort the use of special d isinfectant p roced ures or peri-
tric circles beginning at the area of the p rop osed incision od ic closing of an op erating room if a d irty op eration has
and w orking ou t to the p eriphery of the field . The area p re- been p erform ed . Sticky m ats on the floor at the entrance to
pared shou ld be w id e and should inclu d e room to extend op erating room s d o not red u ce the nu m ber of organisms
the incision, p lace d rains, or create new incisions if neces- on shoes, stretcher w heels, or flat su rfaces in the op erating
sary. There are a variety of antiseptic agents that can be room , and d o not red u ce the incid ence of SSI (4).
used to d ecrease the bacterial counts on the skin. These
includ e p ovid one iod ine, chlorhexid ine, and alcohol con- Instrument Sterilization
taining p rod u cts as the m ost frequ ently u tilized agents.
There are som e d ata to su ggest su p eriority of chlorhexi- Surgical instru m ents should be sterilized prior to u se to
d ine-based skin p rep aration (33). lim it the introd u ction of bacteria into the w ou nd s. Su rgical
instru m ents can be sterilized by steam u nd er p ressure, d ry
heat, or ethylene oxid e (37). The qu ality of sterilization
■ Operating room environment m u st be rou tinely m onitored to ensu re ad equ ate elim ina-
The op erating room is d esigned as a sterile environm ent to tion of m icrobial contam ination. A biological ind icator
try to m inim ize the contam ination of the op erative w ou nd m u st be u sed for m icrobial m onitoring of steam au toclave
by environm ental bacteria. For this reason, the operating p erform ance.
su ite has featu res d esigned to lim it the available bacteria. Flash sterilization of surgical instrum ents is the u se of
rap id steam sterilization for im m ed iate instru m ent u se
Ventilation (4,38). This im m ed iate sterilization is often u sed d u ring an
Room air can contain bacteria lad en d u st, lint, exfoliated op eration for instru ments that have not been sterilized , or
skin, or resp iratory d rop lets. To try to lim it this, op erating that have been d rop p ed or otherw ise contam inated d u ring
room s are m aintained at a p ositive pressure relative to cor- the p roced u re. Flash sterilization is not recom m end ed for
rid ors and ad jacent areas (34). This p revents airflow from routine sterilization becau se it d oes not allow for tim ely
less clean areas into the operating room s. The ventilation biological ind icators to m onitor the perform ance of the
system s for the op erating room shou ld have at least tw o fil- sterilizer. These ap p roaches also typ ically u se m inim al ster-
ter bed s in series and be d esigned to p rod u ce a m inim u m ilization cycle p arameters d esigned to sterilize the instru -
of 15 air changes p er hou r (35). This help s to clear any air- m ents in the shortest p eriod of tim e. Flash sterilization
borne contam ination created by p ersonnel in the room . should generally not be u sed as an alternative to p urchas-
The am ou nt of airborne contam ination in the room is ing ad d itional instru m ent sets or m erely to save tim e
affected by the nu m ber of people m oving around in the betw een op erations (4). In ad d ition, flash sterilization is not
room as w ell as the nu m ber of tim es that the d oor to the recom m end ed for im plantable d evices becau se of the
room is op ened . Lim itation of these activities to only those p otential for seriou s infection. Thu s, all su rgical instru-
necessary is im portant. m ents shou ld be conventionally sterilized p rior to rou tine
Ad d itional m echanism s to try to d ecrease the airborne u se, and flash sterilization shou ld be lim ited to the tru ly
contam ination in operating room s can includ e the u se of u rgent or em ergent need for sterilization or resterilization
lam inar airflow d esigns. This m oves particle-free air over of equ ip m ent.
the asep tic op erating field at a u niform velocity sw eep ing
aw ay any p articles in its path (34). These system s have
been stu d ied only in orthoped ic proced u res w here there
■ Operating room personnel
d oes seem to be som e sm all bu t real further d ecrease in SSI Specific rituals in the operating room are established to
risk beyond the u se of other efforts. Another strategy that p rotect the patient from contam ination by bacteria carried
has been u sed is intraoperative ultraviolet rad iation to try by the healthcare w orkers and also to protect the healthcare
to sterilize the air w ithin the op erating room ; this d oes not w orkers from contam inants carried by the p atient. Atten-
app ear to d ecrease overall SSI risk based on prosp ective tion to these activities is im portant to m aintain a safe envi-
d ata (4). ronm ent.
Surgical Scrub There have been SSI ou tbreaks traced to bacteria carried in
Mem bers of the su rgical team w ho are d irectly involved in the hair.
the op eration and the hand ling of the sterile instru m ents Shoe covers d o not d ecrease the risk of SSI or d ecrease
used in the field m u st perform som e su rgical scru b p rior to the bacteria cou nts on the op erating room floor (45). H ow -
covering w ith su rgical gow n and gloves. The p u rp ose of ever, OSH A regu lations recomm end shoe covers w henever
the su rgical scru b is to d ecrease or elim inate bacteria from gross contam ination of the w earer is likely (36).
the hand s and arm s to lim it the p ossibility of transm ission Sterile Gloves and Gown
to the op erative w ound (39). Cu rrently in the United States,
most surgical personnel skin p reparation is d one u sing After the su rgical scru b, the op erating room p ersonnel w ho
either povid one iod ine solu tions or chlorhexid ine glu- w ill be in d irect contact w ith the operating room field d on a
conate solu tion (40). Outsid e of the United States, the u se of su rgical gow n and sterile gloves (39,46). These are w orn to
alcohol-based agents is the stand ard , although this is gain- m inim ize transm ission of m icroorganisms from the hand s
ing u se in the United States (41). Any of these ap p roaches and arm s of team m em bers to the p atient, as w ell as to pre-
app ear to have the capability of d ecreasing the hand bacte- vent contam ination of the team m em bers w ith the patient’s
rial colony cou nts (40,42). It is im portant that, w hatever blood and bod y flu id s (36). If the glove is p unctured or
skin p rep aration is selected , it be used in accord ance w ith torn, it shou ld be changed p romp tly. Wearing tw o pairs of
its instru ctions to obtain optim al effect. gloves d ecreases the incid ence of healthcare w orker contact
Scru bbing technique, the d u ration of the scru b and the w ith p atients’ blood or bod y flu id s, w hen com pared to
techniqu es u sed for d rying and gloving can all affect the only w earing a single p air of gloves (47). Sim ilarly, the ster-
colony cou nts on the hand s (39). Recent d ata show that a ile gow n creates a barrier betw een the su rgical field and the
shorter (e.g., tw o m inu te) hand preparation is as effective healthcare w orkers’ arm s and torso. The role of the gow ns
as the trad itional ten-m inute hand scru b to red uce bacterial is also to p rotect the healthcare w orkers from exp osu re to
colony cou nts (43,44). It is also clear that the initial scru b of the patient’s blood and bod y flu id s.
an op erating d ay shou ld includ e thorou gh cleaning u nd er-
neath the fingernails as this is a site of entrapped bacterial ■ Antibiotic prophylaxis
load .
Antibiotic p rophylaxis is best d elivered as a very short
cou rse of effective antim icrobial agent d elivered ju st p rior
Surgical Garb and Gloves to op erative incision. This cou rse is not attem pted to steril-
Op erating room p ersonnel typ ically w ear a w ork u niform ize tissu es, bu t if tim ed correctly can d ecrease the d ose
inclu d ing scru b p ants, shirts, or d ress (45,46). These are fre- of w ou nd contam inant exp erienced by the patient. It is
qu ently maintained and laund ered by the hosp ital. There im p ortant to p rovid e the antim icrobial shortly before inci-
are no stu d ies that evaluate the w earing or hand ling of the sion so that effective concentrations are obtained at the
scru b su it as it relates to SSI risk. H ow ever, Occu p ational incision site.
Safety and H ealth Ad m inistration (OSH A) regu lations There are fou r im p ortant p rincip les that m ay m axim ize
requ ire that soiled or contam inated scru b su its be changed the effectiveness of an antim icrobial p rop hylaxis plan (4).
for the p rotection of the w earer. Many institutions have First, the chosen agent m u st be u sed for every patient in
policies regard ing the lau nd ering of the scrub su its, and the w hom there are d ata that the u se of antim icrobial p rophy-
w earing of the su its ou tsid e of the op erating room or ou t- laxis is effective, or for those p roced u res after w hich an
sid e of the facility (45). There are not d ata to su p p ort any infection w ou ld be a catastrop hic event. Second , the chosen
particu lar p olicies. antibiotic agent shou ld id eally be safe, inexp ensive, and
Sim ilarly, su rgical m asks have been w orn to try to lim it bactericid al for the likely m icrobiologic w ound contam i-
bacteria from the operative personnel from contam inating nants for the p lanned op eration. Third , the cou rse of antibi-
the air in the op erating room (45). H ow ever, the efficacy of otics should be very brief but timed to provide a bactericid al
this is u np roven. The m ain benefit of the surgical m ask concentration of d ru g in the seru m and tissu es at the
may be in p rotecting the w earer from exposure to blood or m om ent of incision and throu gh the op eration. Fou rth, the
bod y flu id s that m ay splash d u ring the proced u re. In ad d i- therapeutic levels of the antim icrobial agent should be
tion, OSH A regu lations requ ire that not only the m ask be m aintained u ntil ju st a few hou rs follow ing the closu re of
w orn to p rotect the w earer bu t that eye protection be w orn the incision. Continu ation of antibiotics beyond that tim e is
to p rotect the eyes from sp lashes (36). For patients w ith not necessary and d oes not fu rther d ecrease the w ou nd
special infectiou s risks, m ore d ensely filtering m asks m ay infection rate.
be u sefu l, to p rotect the healthcare personnel from exp o- The selection of antim icrobial agents can be gu id ed by
sure to tu bercu losis, for exam p le. the likely infections that can occur w ith the proced ure
Su rgical cap s and hood s are w orn by su rgical p ersonnel (Table 14.3). The op tions listed in the table are com monly
to d ecrease the contam ination of the field by hair or d ead recom m end ed , bu t are not exclu sively effective. Any
skin from the scalp (45). These are inexpensive m ethod s antibiotic choices and regim ens that conform to the p rinci-
that ap p ear to be effective in p reventing this p roblem . p les noted above should be useful.
For p roced u res that have very low rates of SSI, antimi- incision (4). If the incision has been closed w ith a nonocclu-
crobial p rop hylaxis m ay not be u sefu l. Exam p les of these sive techniqu e, su ch as su tu res, skin tap es, or staples, then
proced u res inclu d e clean op erations in areas of high resist- a sterile d ressing shou ld cover the w ou nd for 24 to 48
ance to infection, su ch as thyroid operations, parathyroid hou rs. Beyond 48 hou rs, a p rim arily healing w ou nd is m ost
op erations, and sim p le hernia operations. H ow ever, the likely sealed to the ou tsid e environm ent and so further
alteration of the host imm u ne d efenses, the u tilization of contam ination shou ld not occu r. Other w ou nd closu re
foreign bod y for som e proced u res, or the presence of other strategies m ay avoid the need for the p ostop erative d ress-
risk factors, m ay increase the risk of SSI to the extent that ing by sealing the w ound at the com pletion of the op era-
prophylactic antibiotics cou ld be u sefu l. For m ost of these tion. For instance, u se of occlu sive su rgical glu e d ressings
situations, su fficient prosp ective d ata to make firm recom - avoid s the need for this step .
m end ations based on level 1 evid ence d o not exist.
■ TREATMENT OF SURGICAL SITE INFECTION
■ Operative care Once SSIs occu r, their treatm ent consists of tw o aspects.
The proper operative technique and care of the patient is an These are the d rainage of infected tissues or flu id s from the
often neglected area of potential benefit in protecting the w ound and the provision of ap propriate antim icrobial
patient from SSI. The technique of operation should be therap y (51,52).
designed to minimize the length of operation, limit the oper- Superficial incisional w ound infections m ay occasionally
ative procedure to the task at hand, minimize the amount of be treated by antimicrobial therapy alone (53,54). If the inci-
dead space and d evitalized tissue created during the opera- sion has erythema surround ing it and no evidence of
tion, as w ell as to limit the amount of contamination in the sw elling or fluid collection, then antibiotic therapy may be
w ound (4). All of these issues should d ecrease the risk of SSI. effective. H ow ever, often skin and subcutaneous infections
involve d evitalized tissue and fluid collection. In this case,
Drains/Dead Space Management the best treatment is opening the affected portion of the
A particularly vexing issu e can be the management of d ead w ound and draining out the infected fluid (53,54). A very
space w ithin the abd om en, chest, or su bcu taneou s tissu es short course of antibiotics may be then necessary to decrease
(48,49). These areas w here d evitalized tissu e or fluid m ay the surrounding cellulitis. Once the erythema has resolved,
accu m u late can be fertile sites for bacterial grow th and the antimicrobial therapy is not generally necessary. These infec-
creation of a SSI. If p ossible, the op erative strategy shou ld tions are typically from skin flora, such as S. aureus and coag-
includ e a w ay to obliterate such d ead sp ace. This can, at ulase-negative staphylococci. The same antibiotics that are
tim es, be d one by allow ing other norm al tissues to collap se useful in the prophylaxis against these infections are gener-
into this area. Alternatively, it m ay require the placem ent of ally useful for their treatment (Table 14.3).
closed su ction d rains to evacuate the fluid that w ould oth- For d eep incisional w ou nd infections, w ou nd opening
erw ise collect there. Evacu ation of this fluid tem p orarily and d ebrid em ent of the affected tissu e is nearly alw ays
may allow the norm al healing tissu es to becom e ad herent necessary. Antibiotics alone are inad equ ate at effectively
and elim inate this p otential d ead space. The u se of closed treating these infections. The p recise ap p roach d ep end s on
suction d rains rather than open d rains is preferable (48,49). the site of the infection. For com m on abd om inal w ound
Op en d rains allow bacteria to enter the su rgical site m ore infections, op ening of the skin and su bcu taneous tissue
easily and thu s increase the bacterial load and potential for and d ebrid em ent of the u nd erlying affected m u scle and
infection. fascia is often necessary (53). This d ebrid em ent may be car-
ried ou t acu tely by sharp d ebrid em ent, or m ore chronically
Tissue Handling by serial d ressing changes to the op en w ou nd (55). Antim i-
Prop er op erative techniqu e inclu d es gentle hand ling of the crobial therap y shou ld again be p rovid ed acu tely for the
tissu es and avoid s the creation of d evitalized tissu e in the ap p rop riate bacteria likely to be involved . Long-term
w ound . Clean d issection of the p lanes, w hen p ossible, and antibiotic therap y is not generally necessary once the sur-
d ebrid em ent of d evitalized tissue is imp ortant to d im inish- rou nd ing skin erythem a has resolved . Persistent infection
ing the p otential for postop erative SSI. Although this p he- in the w ou nd is m ore likely d u e to p ersistent d evitalized
nomenon is extraord inarily d ifficu lt to stud y prospectively, tissu e or foreign bod y, rather than inad equ ate antim icro-
in retrosp ective analysis, the presence of d evitalized tissu e bial therapy.
in a w ou nd greatly increases the risk of perioperative Management of organ space infections is typically now
w ound infection (50). ap proached by p ercutaneou s catheter d rainage of the site of
infection, w ith concomitant ap prop riate antimicrobial ther-
ap y (56). Again, the specific approach d ep end s on the site of
■ Incision care infection. For the most intraperitoneal abscesses, localiza-
The care of the p ostop erative incision varies d ep end ing on tion by com p uted tom ography or u ltrasou nd exam ination
the typ e of closu re ap plied . The principle is to m inim ize the can then help guid e percutaneous placement of a d rainage
contam ination that m ay enter the surgical site through the catheter. The catheter d rainage is intend ed to completely
em pty the cavity of fluid and to attem pt to have the poten- 12. Schaberg DR, Cu lver DH , Gaynes RP. Major trend s in the m icrobial eti-
ology of nosocom ial infection. Am J Med 1991;91(3B):16.
tial space obliterated by the surround ing normal tissues 13. H olley DT, Tou rsarkissian B, Vasconez H C, et al. The ram ifications of
(51,53). If the infected fluid or tissue cannot be removed im m ed iate reconstruction in the m anagem ent of breast cancer. Am Surg
through a catheter, then open d rainage and d ebrid em ent 1995;61(1):60–65.
14. Beitsch P, Balch C. Op erative m orbid ity and risk factor assessm ent in
may be necessary. Again, appropriate antim icrobial therapy m elanom a patients u nd ergoing ingu inal lym p h nod e d issection. Am J
should be d elivered until the patient has clear evid ence of Surg 1992;164(5):462–465.
resolving systemic infection, includ ing fever and leukocyto- 15. N agachinta T, Stephens M, Reitz B, et al. Risk factors for su rgical-
w ou nd infection follow ing card iac su rgery. J Infect Dis 1987;156(6):
sis. H ow ever, the persistence of these find ings is more likely 967–973.
d ue to und rained or und etected sites of infection rather 16. Post S, Betzler M, von Ditfu rth B, et al. Risks of intestinal anastom oses
than inad equate antimicrobial therapy. in Crohn’s d isease. Ann Surg 1991;213(1):37–42.
17. Greif R, Akca O, H orn EP, et al. Su p p lem ental p eriop erative oxygen to
The m anagem ent of SSIs, com plicated by tissu e loss, red u ce the incid ence of su rgical-w ou nd infection. Ou tcom es Research
foreign bod ies and infection of chronically d am aged or Grou p .[see com m ent]. N Engl J Med 2000;342(3):161–167.
poorly vascu larized tissu e (sternal infections, infections in 18. Akca O, Melischek M, Scheck T, et al. Postop erative p ain and su bcu ta-
neou s oxygen tension. Lancet 1999;354(9172):41–42.
irrad iated tissu es, or infections in areas after m u ltip le p ro- 19. Arkilic CF, Taguchi A, Sharm a N , et al. Su p p lem ental p eriop erative
ced ures) may requ ire creative ap proaches to supply nor- flu id ad m inistration increases tissu e oxygen p ressu re.[see com m ent].
mal, vascu larized tissue to the area to clear the infection Surgery 2003;133(1):49–55.
20. Slim K, Vicau t E, Panis Y, et al. Meta-analysis of rand om ized clinical tri-
and heal the w ou nd . This m ay require ped icled or free tis- als of colorectal surgery w ith or w ithou t m echanical bow el p repara-
sue transfer from other sites in the patient, to achieve tion. Br J Surg 2004;91(9):1125–1130.
w ou nd coverage and healing. Experience and sou nd su rgi- 21. Bu cher P, Merm illod B, Morel P, et al. Does m echanical bow el p rep ara-
tion have a role in preventing postoperative com p lications in elective
cal jud gm ent are necessary for consistent success in these colorectal surgery? Swiss Med Wkly 2004;134(5–6):69–74.
d ifficu lt situ ations. 22. Gu enaga KF, Matos D, Castro AA, et al. Mechanical bow el p rep aration
for elective colorectal su rgery. Cochrane Database Syst Rev 2003(2):
CD001544.
■ SUMMARY 23. Zelenitsky SA, Ariano RE, H ard ing GK, et al. Antibiotic p harm acod y-
nam ics in su rgical prophylaxis: an association betw een intraoperative
SSIs can com p licate nearly every op erative intervention. antibiotic concentrations and efficacy. Antimicrob Agents Chemother
2002;46(9):3026–3030.
Know led ge of the risk of infection, the m icrobiology of 24. Lew is RT. Oral versu s system ic antibiotic p rop hylaxis in elective colon
likely infections, and the effective preventive m easu res is su rgery: a rand om ized stu d y and m eta-analysis send a m essage from
necessary to m inimize the p otential for this com plication in the 1990s. Can J Surg 2002;45(3):173–180.
25. H ayek LJ, Em erson JM, Gard ner AM. A p lacebo-controlled trial of the
any ind ivid u al p atient. effect of tw o preop erative baths or show ers w ith chlorhexid ine d eter-
gent on p ostoperative w ou nd infection rates. J Hosp Infect 1987;10(2):
165–172.
■ REFERENCES 26. Pau lson DS. Efficacy evalu ation of a 4% chlorhexid ine glu conate as a
fu ll-bod y show er w ash. Am J Infect Control 1993;21(4):205–209.
1. Ed w ard s JR, Peterson KD, Mu Y, et al. N ational H ealthcare Safety N et- 27. Cru se PJ, Foord R. The ep id em iology of w ou nd infection. A 10-year
w ork (N H SN ) rep ort: d ata su m m ary for 2006 throu gh 2008, issu ed prosp ective stud y of 62,939 w ou nd s. Surg Clin North Am 1980;60(1):
Decem ber 2009. Am J Infect Control 2009;37(10):783–805. 27–40.
2. H oran TC, Em ori TG. Definitions of key term s u sed in the N N IS Sys- 28. Serop ian R, Reynold s BM. Wou nd infections after p reop erative d ep ila-
tem . Am J Infect Control 1997;25(2):112–116. tory versu s razor preparation. Am J Surg 1971;121(3):251–254.
3. H oran TC, Gaynes RP, Martone WJ, et al. CDC d efinitions of nosoco- 29. H am ilton H W, H am ilton KR, Lone FJ. Preop erative hair rem oval. Can J
m ial surgical site infections, 1992: a m od ification of CDC d efinitions of Surg 1977;20(3):269–275.
surgical w ound infections. Infect Control Hosp Epidemiol 1992;13(10): 30. Ko W, Lazenby WD, Zelano JA, et al. Effects of shaving m ethod s and
606–608. intraoperative irrigation on suppu rative m ed iastinitis after bypass
4. Mangram AJ, H oran TC, Pearson ML, et al. Gu id eline for p revention of operations. Ann Thorac Surg 1992;53(2):301–305.
surgical site infection, 1999. Centers for Disease Control and Preven- 31. Moro ML, Carrieri MP, Tozzi AE, et al. Risk factors for su rgical w ou nd
tion (CDC) H osp ital Infection Control Practices Ad visory Com m ittee. infections in clean surgery: a m u lticenter stu d y. Italian PRIN OS Stu d y
Am J Infect Control 1999;27(2):97–132. Grou p . Ann Ital Chir 1996;67(1):13–19.
5. Krizek TJ, Robson MC. Biology of su rgical infection. Surg Clin North 32. Winston KR. H air and neu rosu rgery.[see com m ent]. Neurosurgery
Am 1975;55(6):1261–1267. 1992;31(2):320–329.
6. N apolitano LM. Persp ectives in su rgical infections: w hat d oes the 33. Darou iche RO, Wall MJ Jr, Itani KMF, et al. Chlorhexid ine-alcohol ver-
futu re hold ? Surg Infect (Larchmt) 2010;11(2):111–123. su s p ovid one-iod ine for su rgical-site antisep sis. N Engl J Med 2010;
7. H end erson B, Poole S, Wilson M. Bacterial m od u lins: a novel class of 362(1):18–26.
viru lence factors w hich cau se host tissu e p athology by ind u cing 34. Chow TT, Yang XY. Ventilation p erform ance in op erating theatres
cytokine synthesis [Review ]. Microbiol Rev 1996;60(2):316–341. against airborne infection: review of research activities and p ractical
8. H end erson B, Poole S, Wilson M. Microbial/ host interactions in health gu id ance. J Hosp Infect 2004;56(2):85–92.
and disease: who controls the cytokine netw ork? [Review ]. Immunophar- 35. Architects AIO. Guidelines for design and construction of hospital and health
macology 1996;35(1):1–21. care facilities. Washington: Am erican Institu te of Architects Press; 1996.
9. Latham R, Lancaster AD, Covington JF, et al. The association of d ia- 36. Anonym ou s. Occup ational exp osu re to blood borne p athogens–OSH A.
betes and glu cose control w ith su rgical-site infections am ong card io- Final ru le. Fed Regist 1991;56(235):64004–64182.
thoracic su rgery p atients.[see com m ent]. Infect Control Hosp Epidemiol 37. Association of p eriOp erative Registered N u rses. Recom m end ed p rac-
2001;22(10):607–612. tices for cleaning and caring for su rgical instrum ents and pow ered
10. Gil-Egea MJ, Pi-Su nyer MT, Verd agu er A, et al. Su rgical w ou nd infec- equ ip m ent. AORN J 2002;75(3):627–630.
tions: p rosp ective stu d y of 4,468 clean w ou nd s. Infect Control 1987; 38. Bold ing B. Flash sterilization (steam ). Can Oper Room Nurs J 2003;
8(7):277–280. 21(1):31–33.
11. N ational N osocom ial Infections Su rveillance (N N IS). System Rep ort, 39. Association of p eriOperative Registered N u rses Recom m end ed Prac-
d ata su m m ary from Janu ary 1992 throu gh Ju ne 2003, issued Au gust tices C. Recom m end ed p ractices for su rgical hand antisep sis/ hand
2003. Am J Infect Control 2003;31(8):481–498. scru bs. AORN J 2004;79(2):416–418.
40. Pau lson DS. Com parative evalu ation of five su rgical hand scru b prepa- 48. Dougherty SH , Sim m ons RL. The biology and p ractice of su rgical
rations. AORN J 1994;60(2):246. d rains. Part 1. Curr Probl Surg 1992;29(8):559–623.
41. Gru end em ann BJ, Bjerke N B. Is it tim e for bru shless scru bbing w ith an 49. Dougherty SH , Sim m ons RL. The biology and p ractice of su rgical
alcohol-based agent? AORN J 2001;74(6):859–873. d rains. Part II. Curr Probl Surg 1992;29(9):633–730.
42. Larson EL, Aiello AE, H eilm an JM, et al. Com p arison of d ifferent 50. Weigelt JA, H aley RW, Seibert B. Factors w hich influ ence the risk of
regim ens for su rgical hand p rep aration. AORN J 2001;73(2):412– w ou nd infection in trau m a p atients. J Trauma 1987;27(7):774–781.
414. 51. Fry DE. The econom ic costs of su rgical site infection. Surg Infect
43. O’Shau ghnessy M, O’Malley VP, Corbett G, et al. Op tim u m d uration of (Larchmt) 2002;3(Su p pl 1):S37–S43.
su rgical scrub-tim e. Br J Surg 1991;78(6):685–686. 52. Colizza S, Rossi S. Antibiotic p rop hylaxis and treatm ent of su rgical
44. Deshm u kh N , Kram er JW, Kjellberg SI. A com p arison of 5-m inu te p ovi- abd om inal sep sis. J Chemother 2001;13 Sp ec N o 1(1):193–201.
d one-iod ine scru b and 1-m inu te p ovid one-iod ine scru b follow ed by 53. Pollock AV. The treatm ent of infected w ou nd s [Review ]. Acta Chir
alcohol foam . Mil Med 1998;163(3):145–147. Scand 1990;156(8):505–513.
45. Anonym ou s. Recom m end ed p ractices for su rgical attire. Association of 54. Rogers PN , Wright IH . Postop erative intra-abd om inal sep sis. Br J Surg
Op erating Room N urses. AORN J 1998;68(6):1048–1052. 1987;74(11):973–975.
46. Association of p eriOp erative Registered N u rses. Recom m end ed p rac- 55. Thom as S. Alginate d ressings in su rgery and w ou nd m anagem ent: Part
tices for selection and u se of su rgical gow ns and d rap es. AORN J 2003; 3. J Wound Care 2000;9(4):163–166.
77(1):206–210. 56. Fry DE. N oninvasive im aging tests in the d iagnosis and treatm ent of
47. Tw om ey CL. Dou ble gloving: a risk red u ction strategy. Jt Comm J Qual intra-abd om inal abscesses in the p ostop erative p atient. Surg Clin North
Saf 2003;29(7):369–378. Am 1994;74(3):693–709.
CHAPTER
15
Septic Shock
Awori Hayanga and Stewart Wang
Septic shock is defined as sepsis with hypotension despite for m ore than 8% of all ICU ad m issions (6). The observed
adequate fluid resuscitation combined w ith perfusion abnor- m ortality rate for sep tic shock w as 60%.
malities that might includ e, but are not limited to, lactic aci-
dosis, oliguria, or an acute alteration in mental status.
H yp otension is d efined as a systolic blood p ressu re of
■ PATHOPHYSIOLOGY
90 mm H g or a red uction of 40 mm Hg from the baseline Over the p ast 10 years the m olecu lar m echanism s u nd erly-
in the absence of other causes for the fall in blood pressure, ing the host im m u ne resp onse to infection have begu n to be
or a m ean arterial pressure (MAP) of 65 mm Hg. Patients d ecip hered . The negative and d estru ctive featu res of the
w ho require inotropic or vasopressor support d espite ad e- septic resp onse are the system ic m anifestations of w hat is
quate fluid resuscitation are in septic shock (1–3). otherw ise a p ositive and beneficial local inflam m atory
Septic shock is part of the sp ectru m of clinical responses resp onse to tissu e inju ry. Severe sep sis lead ing to shock
to infection that begins w ith sepsis, progresses tow ard d evelop s becau se of a d ysregu lation in host resp onses,
severe sep sis, and then culm inates in organ d ysfu nction such that the m echanism s initially recru ited to fight infec-
and sep tic shock. Sepsis is the system ic response to infection p rod u ce life-threatening tissu e d am age (7). Infection
tion and rep resents the presence of a system ic inflam m a- starts w ith the invasion and p roliferation of m icroorgan-
tory response together w ith d efinitive evid ence of infection. ism s. This p hase is rap id ly follow ed by host m onocyte/
Infection is d efined as a microbial phenom enon character- m acrop hage recognition of sp ecific m icrobial p rod u cts by a
ized by an inflam m atory response to the presence of fam ily of “p attern-recognition recep tors” that inclu d e the
m icroorganism s or the invasion of norm ally sterile host tis- Toll-like recep tors (TLRs). Lip op olysaccharid e (LPS or
su e by those organism s. System ic inflam m atory resp onse end otoxin) is a com p onent of the cell w all of Gram -nega-
synd rom e (SIRS) is a w id espread inflamm atory response to tive bacteria and is recognized by TLR-4. TLR-2 recognizes
a variety of severe clinical insults. SIRS is manifested by the p eptid oglycan and lip oteichoic acid from Gram -positive
occurrence of tw o or more of the follow ing: (a) tem perature bacteria and zymosan from yeast. Other m em bers of the
38 C or 36, (b) heart rate 90 beats per minute, (c) respi- TLR fam ily sp ecifically recognize flagellin, Cp G-rich bacte-
ratory rate 20 breaths per minute or PaCO2 32 mm Hg, rial DN A, and bacterial lip op ep tid es (8). Monocyte
and (d) white blood cells (WBC) 12,000 per mm (3) or less exp ressed class II m ajor histocom p atibility com p lex m ole-
than 4,000 per mm (3) or immature (band) forms accounting cu les and the d om ains of the T-cell recep tor bind bacterial
for more than 10% of the neutrophils present. Septic shock exotoxins (9).
is to be d ifferentiated from severe sepsis. Severe sepsis is In ad d ition to the above-d escribed recep tor system s
sepsis associated w ith organ d ysfunction, hypoperfusion, or fou nd on im m u ne cells, hu m oral p athw ays are also im por-
hypotension. When hypotension persists in a septic patient tant for the recognition of m icrobial p athogens. The com -
despite ad equate fluid resuscitation, septic shock is present. p lem ent system recognizes p athogen-associated m olecular
Each year in the United States, over 650,000 cases of p atterns on bacteria and fu ngi, lead ing to com plem ent acti-
sep sis are d iagnosed , w ith m ore than 100,000 d eaths (4,5). vation and the generation of the C5b-C9 m embrane attack
From an analysis of six m illion hospital d ischarge record s, com p lex, as w ell as C3a and C5a, p ep tid e m ed iators of
the incid ence of severe sepsis is an estim ated 2% of all hos- inflam m ation and p hagocyte recru itm ent. The plasma
pital ad m issions and three cases per 1,000 pop ulation. Data kallikrein–kinin system is activated by negatively charged
gathered from 22 intensive care units (ICUs) arou nd Paris surfaces and prod u ces an array of solu ble m ed iators w ith
betw een 1993 and 2000 show ed that septic shock accou nted neu trop hil-activating and chemotactic p rop erties. Kinino-
gen and brad ykinin, w hich ind u ce vascu lar permeability,
are p art of the cascad e.
Awori Hayanga: University of Michigan H ealth System , In resp onse to d ifferent p athogen p rod u cts, the cells of
Ann Arbor, MI 48109. the im m u ne system p rod u ce m icrobicid al agents and solu-
Stewart Wang: University of Michigan, Ann Arbor, MI ble m ed iators in an effort to elim inate the invad ing
48109. p athogen and to initiate an ad aptive im m une response.
151
The solu ble m ed iators p rod u ced are p roinflam m atory into three categories: (a) hyp ovolemic, (b) card iogenic, and
cytokines, chem okines, prostanoid s, as w ell as reactive (c) d istribu tive.
oxygen and nitrogen species (7). Elevated circu lating levels Hypovolemic shock results from inadequate intravascu-
of these m ed iators lead to p rogressive end othelial d ysfu nc- lar volume and decreased cardiac preload that lead to
tion and m icrovascu lar inju ry. Macrophage-p rod u ced d ecreased cardiac output (CO) and end -organ perfusion.
cytokines ind u ce end othelial cell exp ression of ad hesion Hypovolemic shock is generally due to either loss of blood or
m arkers that in tu rn m ed iate neu trop hil attachm ent, fluid. Blood loss can be secondary to trauma, GI bleeding,
recruitm ent, and p ersistence at inflam m atory sites. Acti- ruptured aortic aneurysm, or other causes. Fluid loss can be
vated leu kocytes, as w ell as bacterial p rod ucts them selves, d ue to intestinal obstruction, pancreatitis, burns, diarrhea, as
also activate the coagulation cascad e. Tissu e factor is w ell as other causes. Cardiogenic shock is due to failure of the
released in response to proinflam m atory cytokines such as heart as a pump. The four major causes of cardiogenic shock
and interleu kin-1 (IL-1) and lead s to the form ation of are arrhythmias, cardiomyopathies, mechanical abnormali-
throm bin and fibrin clots. Concu rrently, m any end ogenou s ties, and obstructive disord ers. Arrhythmias such as atrial
fibrinolytic m echanism s are im paired because of the fibrillation can suppress CO by d isrupting normal coordina-
release of p lasm inogen-activator inhibitor-1, p rod uction of tion of atrial and ventricular filling and pumping. Brad-
throm bin-activatable fibrinolysis inhibitor, and d ecreased yarrhythmias and heart block can marked ly d ecrease CO and
conversion of p rotein C to the serine p rotease-activated end organ perfusion. Cardiomyopathies, w hether due to
protein C. Activated p rotein C exerts im portant antithrom - ischemic, viral infection, or other reasons, can cause severe
botic, anti-inflam m atory, and profibrinlytic properties by d eficits in myocardial contractility and CO. Mechanical
inactivating factors Va and VIIIa, w hich lim its throm bin causes of pump failure are valvular insufficiency or chord ae
generation and red uces its procoagulant and antifibri- tendineae rupture. Obstructive causes such as pericardial
nolytic p rop erties. Activation of protein C norm ally occu rs tamponad e, massive pulmonary embolism, and tension
by throm bin bou nd to end othelial throm bom od u lin, bu t pneumothorax can also disrupt the heart’s ability to function
throm bomod ulin expression becom es m arked ly im paired as a pump. Abnormally low systemic vascular resistance
w ith p rogressive end othelial d ysfu nction. Altered local causes distributive shock and can be due to a variety of
coagu lation and p rogressive m icrovascu lar throm bosis, in causes. Septic shock is generally classified w ithin the distrib-
conju nction w ith hypotension, lead to tissu e hypop erfu - utive shock category, although it can present with compo-
sion and shock. nents of the other two categories. Aside from septic shock,
Sepsis can be thought of as a process com prising tw o other types of distributive shock are neurogenic shock after
m ajor com p onents, infectiou s and inflam m atory. The clini- central nervous system (CNS) or spinal cord injury, Addison-
cal inflam m atory resp onse extend s from infection to sep sis, ian crisis, myxedema coma, anaphylaxis, and drug or toxin
severe sep sis, and septic shock, w ith clinical ou tcom e p ro- reactions.
gressively w orsening w ith ad vancing stages. In a large
stu d y exam ining the natu ral history of p atients w ith SIRS,
48% w ere fou nd to have infections: 26% had sepsis only,
■ HISTORY
18% d evelop ed severe sepsis, and 4% d eveloped sep tic Patients presenting w ith septic shock m ight be in such d ire
shock (10). Bacterem ia w as increased w ith the severity of cond ition as to be u nable to p rovid e a clear history.
the clinical resp onse. Positive blood cultu res w ere fou nd in N onetheless, it is im p ortant to elicit a history of cu rrent and
17% of p atients w ith sepsis and in 69% of patients w ith sep - recent com plaints from the patient or the patient’s fam ily.
tic shock. Pre-existing cond itions su ch as d iabetes, m alignancy, and
Patients w ith sepsis have a low er m ortality rate com - im m u nosu p p ression are im p ortant to consid er. Current
pared w ith p atients w ith severe sepsis or septic shock m ed ication regim ens as w ell as recent alterations in m ed -
(11–13). The m ortality rate from septic shock is betw een ication m ight p rovid e im p ortant clu es w ith regard to the
35% and 40% in the m onth follow ing onset of sep tic shock. p atient’s u nd erlying p athop hysiology. In su rgical patients
The m ortality from hyp ovolem ic shock varies greatly and p resenting w ith shock, a d etailed su rgical history is essen-
d ep end s on the etiology as w ell as the rapid ity w ith w hich tial. This su rgical history m u st inclu d e not only a list of past
it is recognized and treated (14–16). and p lanned su rgical p roced u res bu t also the u nd erlying
p athology requ iring su rgical intervention. The nature,
extent, and ou tcom e of recent su rgical p roced u res and the
■ EVALUATION
p atient’s periop erative course m u st be taken into consid er-
Shock is the physiologic cond ition in w hich there is inad e- ation as they m ight shed consid erable light on w hy the
qu ate oxygen d elivery. This lead s to cellular hypoxia and p atient is p resenting w ith shock. Was the op eration elective
d isru p tion of necessary biochem ical p rocesses w ith resu lt- or em ergent? Which bod y cavities w ere op ened ? Was it a
ant tissu e and organ d ysfu nction. In the early phases, these clean, contam inated , or d irty op eration? Was a hollow vis-
alterations can be reversed , but they rapid ly become irre- cu s op ened ? Is there an anastom osis? Does the p atient
versible, lead ing to cell d eath, end -organ d am age, m u ltip le have an ind w elling catheter? What is the p atient’s u nd erly-
organ failu re (MOF), and d eath. Shock is broad ly d ivid ed ing cond ition? What are the locations of the p atient’s
Chapter 13 • Septic Shock 153
sym p tom s? What is the natu re of the patient’s com p laints? lactate level, com p lete blood cou nt (CBC) w ith d ifferential,
To w hich organ system s are the com plaints m ost attributa- basic chem istries, am ylase and lip ase, liver fu nction tests,
ble? The d ifferential d iagnosis for a patient presenting w ith card iac enzym es, coagu lation p rofile, fibrinogen, and fibrin
sep tic shock follow ing recent em ergency op eration for sp lit p rod u cts. An u rinalysis and toxicology screen m ight
colonic perforation w ould d iffer greatly from that of a also p rovid e help fu l inform ation. Cosyntrop in challenge or
patient p resenting w ith septic shock 1 year after lu ng trans- cortisol levels can be u sed to d etect ad renal insufficiency. It
plantation. is essential to id entify the cau sative m icrobial p athogen
and the sites of infection. Althou gh sep sis and septic shock
can resu lt from infections at m any sites, the m ost com m on
■ CLINICAL ASSESSMENT
sites are the lu ngs, abd om en, u rinary tract, and skin (27).
The p hysical exam ination shou ld focu s on rap id assess- Blood , sp u tu m , and u rine cu ltu res can be help ful in id enti-
ment of the p atient’s current clinical cond itions, d ifferenti- fying the sou rce of sep sis. Rou tine cu ltu res d raw n on
ating the typ es of shock and d eterm ining the etiology of the p atients on Continu ou s Renal Rep lacem ent Therapy
patient’s shock. Clinical signs of d ecreased global p erfu - (CRRT) have not p roven su ch therap y to be efficaciou s
sion are oligu ria, d elayed capillary refill, cool skin, and in the absence of clinical su ggestion of infection (28). N o
d ecreased level of consciousness in ad d ition to hypoten- clinical d ifference in ou tcom e has been show n betw een
sion. Patients p resenting w ith shock m u st be continu ou sly bronchoalveolar lavage w ith qu antitative cu lture of the
monitored in an ICU setting. For patients in shock, arterial bronchoalveolar-lavage flu id and end otracheal aspiration
catheterization provid es a m ore accu rate m easu re of blood w ith nonqu antitative cu ltu re of the asp irate in the d iagno-
pressu re than noninvasive techniqu es. sis of ventilator associated p neu m onia (VAP) (29). Ad d i-
Althou gh elevated lactate levels can be d ue to cau ses tionally, the grow ing clinical menace p osed by Clostrid ium
other than sep tic shock, efforts to norm alize lactate levels d ifficile w arrants consid eration as a cau se of p resu m ed
by m eans of hem od ynam ic optim ization shou ld be consid - sep sis in the critically ill su rgical p atient (30). For patients
ered (17). The p rognostic value of blood lactate concentra- in shock, a chest x-ray and electrocard iogram are essential
tion has been established in septic shock patients (18,19). for basic assessm ent of the card iop u lm onary system . Im ag-
Gastric tonom etry has been show n to be a p red ictor of m u l- ing stud ies should also be p rom ptly perform ed to id entify
tiorgan d ysfu nction synd rom e and m ortality in p atients the p otential sou rce of infection (31). Plain or contrast rad i-
w ith sep tic shock (20,21). H ow ever, resu scitation of criti- ograp hs and rad ionu clid e stu d ies can be u sed to d eterm ine
cally ill patients on the basis of gastric tonom etry failed to the p resence of su rgical com p lications su ch as visceral p er-
significantly im p rove ou tcom e (22). foration or obstru ction and anastom otic d isru ption. Com -
H em od ynam ic m easu rements can be m ad e in sep tic p u ted tom ograp hy or m agnetic resonance im aging scans
shock p atients u sing p u lm onary artery catheterization. m ight help d etect the p resence of infectiou s foci or flu id
Param eters su ch as CO, pu lm onary artery occlu sion p res- collections.
sure, and system ic vascu lar resistance can be u sefu l in d if-
ferentiating septic shock from other form s of shock.
Pu lm onary artery catheterization can also provid e u sefu l
■ MANAGEMENT
inform ation abou t the ad equ acy of flu id resuscitation, the The essential steps in the m anagem ent of septic shock are
effectiveness of vasopressors and inotropes, and the effect the sam e as those u sed to treat patients w ith m ild or m od -
of m echanical ventilatory sup port on hem od ynam ics (23). erate sep sis: (a) tim ely resu scitation, (b) tim ely d iagnosis of
H ow ever, p u lmonary artery catheterization m ay be fre- the infectiou s focu s, (c) p rom p t antibiotic therapy, and (d )
qu ently associated w ith inaccurate m easu rem ents (24) and exp ed itiou s infectiou s sou rce control. Becau se of the sever-
one retrosp ective analysis su ggested a w orsened clinical ity of the d isease p rocess, these step s m u st be und ertaken
outcom e w ith p u lm onary artery catheterization (25). At concu rrently (Fig. 15.1). Id entification of the infectiou s foci
this tim e, there is no conclusive clinical evid ence abou t the and institu tion of the ap p rop riate antibiotic treatm ent and
utility and p otential benefit of pu lm onary artery catheteri- sou rce control are d iscu ssed in greater d etail in Chapter 14;
zation in sep tic shock. There is a grow ing popularity of the hence, the cu rrent focu s w ill be on resu scitative m easures
Esophageal Doppler Monitor (EDM) w ith its d em onstrable for sep tic shock.
clinical u tility and efficacy in estim ating flu id status and
CO in the critically ill population using noninvasive tech-
niqu es (26).
■ SHOCK
Shock is a m ed ical em ergency and m u st be treated im m ed i-
ately. As w ith any critical p atient, treatment must first
■ LABORATORIES AND STUDIES
ad d ress the ABCs—airw ay, breathing, and circulation. First,
Laboratory tests are helpful to assess the patient’s cond i- the airw ay m u st be assessed and su p p orted . Patients in
tion and evid ence of organ d ysfu nction as w ell as resp onse sep tic shock m ay have a d epressed level of consciou sness
to treatm ent. They can help id entify the etiology of the or encephalopathy and requ ire intu bation for airw ay pro-
patient’s shock. Basic tests includ e arterial blood gas, tection. Second , ventilation and oxygenation shou ld be
S e ps is -induce d hypote ns ion
Be gin fluid re s us cita tion

(crys ta lloid pre fe rre d)a
Blood pre s s ure a cce pta ble
NO YES
Cons ide r CVP or PAC monitoring

Es ta blis h re eva lua tion inte rva l
Continue fluid re s us cita tion until
s ubtle evide nce of intrava s cula r
volume ove rloa d b or CVP 8−14 mm
Hg or PAOP 14−18 mm Hg or S BP
≥90 mm Hg or MAP ≥60−65 mm Hg
S BP ≥90 mm Hg
or MAP ≥60−65
mm Hg
YES NO
Es ta blis h Cons ide r drotre cogin

re eva lua tion the ra py CI ≥3.0
inte rva l
Cons ide r s te roid the ra py
YES or NO
Unknown
Va s opre s s or (nore pi- Vasopres sor (norepi-

ne phrine pre fe rre d) nephrine prefe rred)
ta rge ting S BP ≥90 targeting S BP ≥90 mm
mm Hg or MAP ≥60−65 Hg or MAP ≥60−65
mm Hg mm Hg and
dobutamine ta rgeting
Ct ≥3.0
S BP ≥90 mm Hg or MAP
YES ≥60−65 mm Hg NO
Es ta blis h re eva lua tion inte rva l Cons ide r CVP or PAC
a nd re gula rly a tte mpt to we a n monitoring, if not a lre a dy in
va s opre s s ors to ma inta in blood pla ce .
pre s s ure ta rge t Add s e cond va s opre s s or a ge nt
(cons ide r va s opre s s in .01−.04
units /min).
a 250–1,000 mL bolus e s of crys ta lloid, e a ch ove r 5−15 minute s.
b Ba s ila r cra ckle s on lung a us culta tion or incre a s e in puls e oxime try O 2 s a tura tion.
FIGURE 15.1. Flow diagram for management of septic shock. CVP, central venous pressure; PAC, pulmonary artery catheter; SBP, sys-
tolic blood pressure; MAP, mean arterial pressure. (From Dellinger RP. Cardiovascular management of septic shock. Crit Care Med
2003;31:951, with permission.)
assessed and supp orted as necessary w ith sup plemental as d iffering levels of alp ha-ad renergic and beta-ad renergic
oxygen or mechanical ventilation if ind icated . Third , circu- agonistic activity. The vasop ressors that have been u sed
latory fu nction is assessed and su pp orted w ith volu m e for the treatm ent of sep tic shock are d op am ine, norep i-
expansion and vasop ressors as necessary. By d efinition, nep hrine, p henylep hrine, ep inep hrine, and vasopressin.
patients in sep tic shock have circulatory failu re, and prompt Dop am ine and ep inep hrine are m ore likely to cau se tachy-
treatment is necessary to avoid multiple organ d ysfunction. card ia than norep inep hrine and p henylep hrine. Dopam ine
and norep inep hrine both raise blood p ressu re and CO;
how ever, d op am ine has a greater effect on raising CO than
■ FLUIDS
norep inep hrine (35). Althou gh all the p ressors m entioned
The hyp otension observed in sep tic shock is m u ltifactorial have been u sed to treat sep tic shock, recent rep orts suggest
in origin. Sep sis can cau se m yocard ial d epression and a trend tow ard the p referred u se of norep inephrine. Sev-
d ecreased vasom otor tone. In ad d ition, there m ight be sig- eral stu d ies have fou nd norepinephrine to be m ore effec-
nificant loss of plasm a volum e into the interstitial space, tive than d op am ine in refractory sep tic shock (36,37). In a
resu lting in severe intravascu lar hypovolem ia. Intravascu - p rosp ective stu d y of 97 p atients in sep tic shock, m ortality
lar volu m e should be restored rapid ly u sing boluses w ith w as d ecreased in p atients treated w ith norep inep hrine
careful assessment of the patient’s physiologic status before (62% m ortality) com p ared w ith p atients treated w ith either
and after each bolu s. This volu me resu scitation shou ld be ep inep hrine or high-d ose d op am ine (82% m ortality) (38).
repeated in exped itious fashion until blood pressure and Potential ad vantages of norep inep hrine over d opam ine are
tissue perfusion are returned to normal and tissue hypoxia less tachycard ia and no interference w ith the hypothalam ic
is corrected . Volu m e exp ansion in p atients w ith septic shock p itu itary axis (39,40). The typ ical intravenou s d ose range
must be aggressive, w ith careful monitoring of the patient for norep inep hrine is 1–30 g per m inu te.
to d etermine the end point of fluid resuscitation. When Vasopressin has recently been reported to be effective in
invasive m onitoring is available, fluid resuscitation shou ld the treatm ent of hyp otension in sep tic shock. Plasma levels
be given u ntil a central venou s pressure of 8–14 m m H g or of vasop ressin have been fou nd to be inap p ropriately low
pu lm onary artery occlu sive pressu re of 14–18 m m H g is in p atients w ith sep tic shock (41), p erhap s d u e to exhaus-
achieved . The p atient’s respiratory statu s m ust be m onition of neurohypophyseal stores from prolonged stim ula-
tored closely d u ring this resu scitation as p atients w ith sep - tion or im pairm ent of baroreflex-m ed iated stim ulation of
tic shock have increased pulm onary capillary leak, w hich vasop ressin release (42–44). Vasop ressin therapy to restore
in the setting of increased filling pressu res can lead to norm al circu lating levels has been show n to be effective in
im paired oxygenation. reversing hyp otension in sep tic p atients, enabling w ith-
Volu m e exp ansion can be carried ou t u sing either crys- d raw al of other vasop ressors (45–48). The intravenou s
talloid or colloid solutions. A large nu m ber of clinical stu d - d osing of vasop ressin shou ld be lim ited to 0.01–0.04 u nits
ies have com pared colloid w ith crystalloid resu scitation, p er m inu te as higher d oses increase the risk of splanchnic
bu t there is no clear evid ence that one has significant clini- and coronary artery ischem ia and m ay lead to d ecreases
cal benefit over the other (32–34). Of course, a given volum e in CO (42).
of colloid resu lts in greater exp ansion of the intravascu lar Sep sis can also cau se m yocard ial d ep ression w ith
volu m e than d oes an equ al volu m e of crystalloid . The cost d ecreased global contractility. A nu m ber of m ed iators
of volu m e resu scitation u sing colloid is significantly u p regu lated d u ring sep sis, su ch as tu m or necrosis factor
greater than that u sing crystalloid . alp ha, IL-1, and nitric oxid e, are know n to d ep ress myocar-
d ial contractility (17,49). Sep tic p atients have been d em on-
strated to have red uced ejection fraction and biventricu lar
■ VASOPRESSORS d ilatation (50,51). In the p resence of severe m yocard ial
Once intravascular volume has been ad equately expand ed d ep ression and inad equ ate CO in sep tic shock, d obu ta-
w ith fluid resuscitation, the continued presence of hypoten- m ine therap y can be ad d ed . In the p resence of hypoten-
sion (MAP 65 mm H g) ind icates the need for vasopressors sion, vasop ressors m u st be ad m inistered in ad d ition to the
and inotropic agents. Sep sis can cau se d ecreased vasomotor d obu tam ine. The typ ical d ose range for d obu tam ine is
tone and vasopressors can be used to counteract these 5–15 g p er kg p er m inu te. Attention shou ld also be paid to
effects if necessary to restore norm al blood p ressure, p erfu - the sites su rrou nd ing the intravascu lar catheters being
sion, and oxygenation once intravascular volume has been u sed to ad m inister these m ed ications as they can, like
ad equ ately restored . Exp ansion of intravascular volu me is Foley catheters, be a sou rce of infection (52).
preferred as the first line of therap y as it increases CO and
blood pressu re w ithout seriou sly imp airing gas exchange
(11). Vasopressor therapy may also be need ed prior to ad e-
■ COORDINATED SUPPORTIVE CARE
qu ate intravascu lar volume expansion to m aintain perfu- The Surviving Sep sis Cam paign recently convened a large
sion in the presence of life-threatening hypotension. international p anel of exp erts to d eterm ine the cu rrent best
There are a variety of vasop ressors w ith d iffering p ractices in the clinical treatm ent of sep sis (31). For intu-
effects on card iac and p erip heral vascu lar activity, as w ell bated p atients, the p anel su p p orted the u se of low tid al
volu m e and lim itation of insp iratory p lateau p ressu re to APACH E II scores 25. Former sm okers and less acu tely ill
lessen acu te lu ng inju ry and acute respiratory d istress syn- p atients (APACH E II 25) received significantly less bene-
d rom e (ARDS) (31). Ad d itional supp ortive m easu res that fit from d rotrecogin alfa treatm ent (56,57).
have been show n to be help fu l inclu d e protocols to w ean
ventilation and sed ation/ analgesia as w ell as the m inim al-
ization of neu rom u scu lar blockad e. Tight glycem ic control,
■ CORTICOSTEROIDS
prophylaxis for d eep vein throm bosis and up per GI bleed - There have been a large nu mber of clinical trials exam ining
ing, and asp iration control m easu res such as head of bed corticosteroid therap y for sep sis and sep tic shock. Signifi-
elevation are also essential. cant shortcom ings of these trials inclu d e inconsistent
A recent p rosp ective stud y rand om ized 263 p atients p atient inclu sions criteria, d iffering d ru g d osing regim ens,
presenting w ith sep tic shock to either stand ard control and variable d efinitions for sep sis and sep tic shock. The
therap y or to early goal-d irected therapy (53). Stand ard m ajority of early stu d ies u sed high-d ose steroid s for short
therap y consisted of volu m e resu scitation targeting a cen- d u rations, u su ally 1 d ay (58). More recent stu d ies have u ti-
tral venou s p ressu re of 8–12 m m H g, follow ed by vasop res- lized p hysiologic stress-d ose corticosteroid s for longer
sor therap y to m aintain a MAP of 65 m m H g. Early d u rations. In one recent p rosp ective stu d y p atients w ith
goal-d irected therap y ad d ed m easurem ent of central sep tic shock requ iring catecholam ines for m ore than 48
venou s oxyhem oglobin (CVO2) saturation. Follow ing vol- hou rs w ere rand om ly assigned to receive corticosteroid
um e ad m inistration and vasopressor su pport as in the (hyd rocortisone 100 m g IV TID for 5 d ays) or p lacebo; 68%
stand ard treatm ent group , ad d itional therapy w as based of the 22 p atients receiving corticosteroid therapy w ere
on the CVO2 satu ration. If the CVO2 saturation w as 70%, w eaned off vasop ressors w ithin 7 d ays as op p osed to 21%
blood w as transfu sed to achieve a hem atocrit of 30%. If of 19 p atients receiving p lacebo (59). Desp ite the shorter
CVO2 satu ration rem ained 70% follow ing the transfu - d u ration of catecholam ine d ep end ence, no significant
sion, d obu tam ine w as ad d ed to a m axim um of 20 g p er kg im p rovem ent in m ortality w as observed . Su bsequ ently, a
per m inu te in an attem pt to achieve a CVO2 saturation of larger trial of 300 ad u lts w ith sep tic shock w as cond ucted ,
70%. In-hosp ital m ortality in the early goal-d irected ther- com p aring a 7-d ay cou rse of treatm ent w ith hyd rocorti-
apy grou p w as 30.5%, significantly low er than the sone (50 m g IV every 6 hou rs) and flu d rocortisone (50 m g
observed m ortality rate of 46.5% in the stand ard therap y every d ay) or p lacebo (60). The m ajority (76%) of the stu d y
group (53). This ap p roach of m onitoring the oxygen su p - subjects had evid ence of ad renal insu fficiency as d em on-
ply–d em and relationship d uring therapy of septic shock strated by an increase of 9 g per d L in plasm a cortisol
app ears p rom ising; ad d itional trials are forthcom ing. follow ing cosyntrop in challenge (250 g) (61). Am ong
p atients w ith evid ence of ad renal insu fficiency a treatm ent
■ HUMAN-ACTIVATED PROTEIN C benefit w as noted . The benefits w ere significantly d ecreased
28-d ay mortality (53% vs. 63%) and resolu tion of vasopres-
In 2001 the resu lts of a m u lticenter trial u sing recom binant sor d epend ence (57% vs. 40%). There w as no observed
hu m an-activated p rotein C (d rotrecogin alfa) for the treat- increase in the incid ence of ad verse events. In a recently
ment of sep tic shock w ere pu blished . One thousand , six p ublished systematic review w hich evalu ated the various
hu nd red , and ninety p atients w ere rand om ly assigned to d oses com m only u sed over the past 50 years, a clearly
receive a 96-hou r infusion of d rotrecogin alfa or placebo, d em onstrable benefit in m ortality w as not observed (62).
beginning w ithin 24 hours of p resentation w ith know n or
suspected severe infection and evid ence of shock (54). A
significant im p rovem ent in the 28-d ay m ortality rate w as
■ COMPLICATIONS OF SEPTIC SHOCK
noted in the d rotrecogin-treated group (24.7% vs. 30.8%). Septic shock is an extrem ely severe com plication of m any
Treatm ent w as fou nd to be of greatest benefit in the m ost d isease p rocesses and op erations in su rgical patients,
acu tely ill su bset of p atients w ith an APACH E II score 25. carrying w ith it a very high m ortality rate. If treatm ent is
Drotrecogin alfa treatm ent w as fou nd to be associated w ith su ccessfu l and the p atient su rvives, the m ost com m on
more rap id recovery of card iac and pu lm onary function resu ltant com p lications are failu re of ind ivid u al organ sys-
(55), as w ell as low er incid ence of m u ltiple-organ d ysfu nc- tem s or MOF.
tion. H ow ever, treatm ent w as also associated w ith
increased incid ence of bleed ing com plications, such as fatal
intracranial hem orrhage. The U. S. Food and Drug Ad min-
■ PULMONARY
istration (FDA) su bsequ ently approved d rotrecogin alfa for The lu ngs are the organ system most su sceptible to inju ry
treatm ent of ad u lts w ith septic shock. The estimated cost is from sep tic shock. Acu te lu ng failu re in the setting of su r-
more than $6,000 p er treatm ent cou rse at the su ggested gery and sep sis is know n as ARDS. Desp ite ad vances in
d osing regim en of 24 g per kg per hou r for 96 hours. The m echanical ventilatory assistance and su p p ortive care, the
cost–benefit ratio of d rotrecogin alfa treatm ent has been m ortality rate for ARDS rem ains high. The m ortality asso-
exam ined . The cost p er year of life saved w ith treatm ent is ciated w ith ARDS is greater w hen ARDS is associated w ith
$24,000 to $27,000 for the m ost acutely ill patients w ith m u ltip le trau m a, fat em bolism , or gastric asp iration (63). A
higher incid ence of ARDS is present in patients w ith sep tic coagu lation. Sep sis cau ses d ep letion of antithrom botic p ro-
shock as a resu lt of p u lm onary rather than nonp u lm onary teins su ch as activated p rotein C, and treatm ent w ith acti-
infection (64,65). vated p rotein C has im p roved m ortality and ou tcom e in
Mechanical ventilation is an essential comp onent of p atients w ith sep tic shock.
ARDS treatm ent. Over the past d ecad e m uch attention has The severe system ic inflam m atory resp onse incited
focused on lim iting the ad verse effects of m echanical venti- by infection lead s su bsequ ently to a com p ensatory anti-
lation, w hich are ventilator-ind u ced lung inju ry, barotrau - inflam m atory resp onse in the host. Du ring the tim e w hen
mas or volu traum a, atelecto-trau m a, and biotrau m a this latter anti-inflam m atory resp onse p red om inates, the
(66–68). Mechanical ventilation in ARDS might exacerbate host im m u ne system is less responsive and m icrobial
lung injury by alveolar overd istension or repetitive alveo- p athogens might be able to establish new sites of infection.
lar recru itm ent-d erecruitm ent, thereby increasing alveolar
cap illary perm eability and inflam m atory m ed iator release
(69). Recent trials using low er tid al volu m es to minim ize
■ ENDOCRINE
this d am age have show n im provem ent in su rvival (70). Recent stud ies have reported that patients w ith severe sep-
sis m ight d evelop either relative ad renal insu fficiency or
SIRS-ind u ced glu cocorticoid recep tor resistance (79,80).
■ RENAL Ad renal insufficiency can be d iagnosed w ith a short corti-
Renal d ysfunction is com m only observed in patients w ith cotrophin stimulation test, and treatment of nonrespond ers
sep tic shock. H ypop erfusion second ary to intravascu lar has been effective in reversing septic shock. Plasma levels of
volu m e d ep letion or vasopressors, altered intravascu lar vasopressin have been found to be inapp ropriately low in
coagu lation, and nep hrotoxicity from d rugs such as am ino- p atients w ith septic shock (41), and vasop ressin therapy to
glycosid es are just som e of the contributing factors in restore norm al circulating levels has been show n to be effec-
patients w ith septic shock. The d evelopm ent of oligu ric tive in reversing hypotension in sep tic patients (46–48).
acu te renal failu re places ad d itional stress on other failing Septic patients commonly d evelop hyperglycemia and
organ system s and significantly increases the m ortality rate insulin resistance, w hich increases the risk of complications
of critically ill p atients. Renal replacem ent therap y w ith such as severe infections, critical illness polyneu rop athy,
interm ittent hem od ialysis is the stand ard treatm ent. A MOF, and d eath (81,82). A recent prospective, rand omized ,
recent p rosp ective trial com p ared d aily d ialysis w ith alter- controlled trial examined the effect of intensive insulin ther-
nate-d ay analysis and show ed a significant red uction in apy to normalize blood glu cose in critically ill patients (83).
mortality for early d ialysis (28% vs. 46%) in critically ill There w as significant m ortality red u ction in the intensive
patients, m ost of w hom w ere septic. Patients receiving treatm ent group in w hich blood glu cose w as m aintained
d aily hemod ialysis had better control of u rem ia, few er betw een 4.4 and 6.1 mmol p er L comp ared to the conven-
hyp otensive ep isod es, and m ore rapid resolu tion of acu te tional treatm ent group in w hich blood glu cose w as m ain-
renal failu re (71). tained betw een 10.0 and 11.1 m m ol p er L. Both in-hospital
A large nu m ber of solu ble m ed iators w ith overlapping d eaths and ICU length of stay w ere im proved by intensive
and synergistic biologic effects are released d uring sep tic insulin therapy. Of note, the greatest red uction in mortality
shock. Becau se m u ltiple interventions based on blocking a occu rred from d eaths d u e to MOF w ith a septic focu s.
single med iator have failed to show clinical efficacy, d irect
rem oval of inflam m atory m ed iators from the circu lation is
intu itively attractive (66). This strategy m ight interru p t the
■ GASTROINTESTINAL AND HEPATIC
inflam m atory cascad e and attenuate septic shock and MOF Gastrointestinal ileu s and m alabsorp tion are frequently
(72). Althou gh a few prelim inary trails have show n som e observed in p atients w ith sep tic shock, and m alnutrition is
benefit (73), m u ltiple rand omized controlled trials u sing com m only fou nd in these p atients as w ell. Recent stud ies
continu ou s hem ofiltration or plasm a filtration in septic have show n im p roved ou tcom e w ith early initiation of
patients have show n no im provem ent either in hemod y- enteral feed ings as w ell as the su p eriority of enteral feed -
nam ics or ou tcom e (74–76). ings over total p arenteral nu trition (84,85). Early jeju nal
feed ings m ight help m aintain the norm al bacterial
m icroflora and GI tract barrier fu nction, thereby m inim iz-
■ HEMATOLOGIC
ing bacterial and end otoxin translocation (86). The rate of
Bacterial p rod ucts can d irectly activate the coagu lation cas- septic com plications w as low er in patients treated w ith
cad e. Proinflam m atory cytokines such as and IL-6 that are early jeju nal feed ing com p ared w ith conventional p ar-
released d u ring the host resp onse to infection also activate enteral nu trition (87). The ad d ition of glu tam ine to enteral
coagulation and enhance form ation of throm bin and fibrin and p arenteral feed s m ight im p rove im m u ne cell fu nction
clot (77,78). Circu lating med iators also cau se end othelial and also p reserve intestinal morp hology, thereby preserv-
cell d am age and expression of ad hesion m arkers. All these ing intestinal barrier fu nction (88,89).
processes lead to the u nbalancing of norm al intravascu lar Septic patients being treated with antibiotics are at risk for
coagulation and can resu lt in d isseminated intravascular d evelopment of pseudomembranous colitis. Low perfusion
might also lead to intestinal ischem ia or pancreatitis. Sep tic ■ REFERENCES

patients are at increased risk of stress gastritis and u lcera-
1. Am erican College of Chest Physicians/ Society of Critical Care Med i-
tion. Gastric p H shou ld be m onitored and controlled . cine Consensus Conference: d efinitions for sepsis and organ failure
Cholestatic jau nd ice is also frequ ently observed in severely and gu id elines for the u se of innovative therap ies in sep sis. Crit Care
septic p atients. Bilirubin can becom e elevated above Med 1992;20(6):864–874.
2. Balk RA. Severe sepsis and sep tic shock. Definitions, ep id em iology,
20 m g p er d l. Parenteral nutrition can cause fatty infiltra- and clinical m anifestations. Crit Care Clin 2000;16(2):179–192.
tion of the liver and also contribu te to cholestatic jau nd ice. 3. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ ESICM/ ACCP/
Provision of nu tritional su pport via enteral rather than p ar- ATS/ SIS International Sep sis Definitions Conference. Crit Care Med
2003;31(4):1250–1256.
enteral feed ings can d ecrease this com plication. Cholesta- 4. Martin GS, Mannino DM, Eaton S, et al. The ep id em iology of sep sis in
sis and hyp op erfu sion from sep tic shock m ight contribu te the United States from 1979 throu gh 2000. N Engl J Med 2003;348(16):
to the d evelop m ent of acalcu lou s cholecystitis. 1546–1554.
5. Angu s DC, Lind e-Zw irble WT, Lid icker J, et al. Ep id em iology of severe
sep sis in the United States: analysis of incid ence, ou tcom e, and associ-
■ NEUROLOGIC
ated costs of care. Crit Care Med 2001;29(7):1303–1310.
6. Annane D, Aegerter P, Jars-Gu incestre MC, et al. Cu rrent ep id em iology
of sep tic shock: the CUB-Rea N etw ork. Am J Respir Crit Care Med 2003;
The nervou s system is an active p articip ant in the system ic 168(2):165–172.
response to sep sis. Recent exp erim ental stu d ies have 7. Lolis E, Bucala R. Therap eu tic ap p roaches to innate im m u nity: severe
show n that afferent vagal nerve stim u lation d u ring sep sis sep sis and sep tic shock. Nat Rev Drug Discov 2003;2(8):635–645.
8. Ad erem A, Ulevitch RJ. Toll-like recep tors in the ind u ction of the innate
increases the secretion of corticotrophin-releasing hor- im m u ne response. Nature 2000;406(6797):782–787.
mone, ad renocorticotrop ic horm one (ACTH ), and cortisol 9. Pap ageorgiou AC, Acharya KR. Microbial su p erantigens: from stru c-
(90). In a m ou se m od el of end otoxem ia, vagal nerve stim u - ture to fu nction. Trends Microbiol 2000;8(8):369–375.
10. Brun-Buisson C, Doyon F, Carlet J. Bacterem ia and severe sep sis in
lation prevented the onset of shock in anim als follow ing ad u lts: a m ulticenter p rosp ective su rvey in ICUs and w ard s of 24 hos-
vagotomy (91). System ic sepsis com m only prod u ces brain p itals. French Bacterem ia-Sep sis Stu d y Grou p . Am J Respir Crit Care
d ysfunction, sep sis-associated encephalop athy, w hich can Med 1996;154(3 Pt 1):617–624.
11. Bone RC, Fisher CJ Jr, Clem m er TP, et al. A controlled clinical trial of
vary from a transient, reversible encep halopathy to irre- high-d ose m ethylpred nisolone in the treatm ent of severe sep sis and
versible brain d am age. The encephalopathy in the acu te sep tic shock. N Engl J Med 1987;317(11):653–658.
phase clinically resem bles m any m etabolic encep halo- 12. Dhainau t JF, Vincent JL, Richard C, et al. CDP571, a hu m anized anti-
bod y to hum an tu m or necrosis factor-alp ha: safety, p harm acokinetics,
pathies: a d iffu se d isturbance in cerebral function w ith im m une response, and influ ence of the antibod y on cytokine concen-
sparing of the brain stem . The severity of the encephalop a- trations in patients w ith sep tic shock. CPD571 Sep sis Stu d y Grou p . Crit
thy, as reflected in progressive electroencephalogram Care Med 1995;23(9):1461–1469.
13. Bone RC, Balk RA, Fein AM, et al. A second large controlled clinical
(EEG) abnorm alities, often preced es, and then parallels, stu d y of E5, a m onoclonal antibod y to end otoxin: resu lts of a p rosp ec-
d ysfunction in other organs (92). tive, m u lticenter, rand om ized , controlled trial. The E5 Sep sis Stu d y
Group . Crit Care Med 1995;23(6):994–1006.
14. Shoem aker WC. Tem p oral p hysiologic p atterns of shock and circu la-
■ MULTIPLE-ORGAN FAILURE tory d ysfunction based on early d escriptions by invasive and noninva-
sive m onitoring. New Horiz 1996;4(2):300–318.
15. Talm or D, Greenberg D, H ow ell MD, et al. The costs and cost-effective-
The incid ence of MOF or d ysfu nction varies d ep end ing on ness of an integrated sep sis treatm ent p rotocol. Crit Care Med 2008;
the d efinition and classification schem e u sed (93). The m ost 36(4):1168–1174.
com m only u sed MOF score is that of Knau s et al., w hich 16. Shorr AF, Micek ST, Jackson WL Jr, et al. Econom ic im p lications of an
evid ence-based sepsis protocol: can w e im prove outcom es and low er
uses objective d efinitions for five-organ system failu res costs? Crit Care Med 2007;35(5):1257–1262.
(94). They rep orted in 1985 that a single-organ system fail- 17. Ru okonen E, Parviainen I, Uu saro A. Treatm ent of im p aired p erfu sion
ure w as associated w ith 40% m ortality, tw o organ system in sep tic shock. Ann Med 2002;34(7–8):590–597.
18. Fried m an G, Berlot G, Kahn RJ, et al. Com bined m easu rem ents of
failu res w ere associated w ith 60% m ortality, and three or blood lactate concentrations and gastric intram u cosal p H in p atients
more organ system failu res lasting m ore than 3 d ays w ere w ith severe sep sis. Crit Care Med 1995;23(7):1184–1193.
associated w ith 98% m ortality (94). MOF is often the final 19. Vincent JL, Du faye P, Berre J, et al. Serial lactate d eterm inations d u ring
circu latory shock. Crit Care Med 1983;11(6):449–451.
com plication of critical illness and is the lead ing cause of 20. Maynard N , Bihari D, Beale R, et al. Assessm ent of sp lanchnic oxy-
d eath in p atients ad m itted to an ICU (93,95,96). genation by gastric tonom etry in p atients w ith acu te circu latory failu re.
Severe sep sis and sep tic shock are the m ost com m on JAMA 1993; 270(10):1203–1210.
21. Marik PE. Gastric intram u cosal p H . A better p red ictor of m u ltiorgan
cau ses of MOF (95). Although outcom e follow ing the onset d ysfu nction synd rom e and d eath than oxygen-d erived variables in
of MOF has im p roved slightly in the last several d ecad es p atients w ith sep sis. Chest 1993;104(1):225–229.
and new therap ies app ear to hold prom ise, p revention 22. Gom ersall CD, Joynt GM, Freebairn RC, et al. Resu scitation of critically
ill p atients based on the results of gastric tonom etry: a p rosp ective, ran-
rem ains the op tim al w ay to treat MOF. Rap id , ad equ ate d om ized , controlled trial. Crit Care Med 2000;28(3):607–614.
volum e resu scitation, and aggressive sup port of d ysfu nc- 23. Mim oz O, Rauss A, Rekik N , et al. Pu lm onary artery catheterization in
tioning organ system s and critical. These m easu res, critically ill patients: a p rospective analysis of outcom e changes associ-
ated w ith catheter-prom p ted changes in therap y. Crit Care Med 1994;
together w ith ap p ropriate antibiotic coverage, control of 22(4):573–579.
the infectiou s sou rce, ad equate nu trition, and aggressive 24. Squara P, Bennett D, Perret C. Pu lm onary artery catheter: d oes the
pulm onary m anagem ent, are im portant for reversing the p roblem lie in the users? Chest 2002;121(6):2009–2015.
25. Connors AF Jr, Sp eroff T, Daw son N V, et al. The effectiveness of right
d ow nw ard physiologic spiral that lead s from sep tic shock heart catheterization in the initial care of critically ill p atients. SUP-
to MOF and d eath. PORT Investigators. JAMA 1996;276(11):889–897.
26. Dark PM, Singer M. The valid ity of trans-esop hageal Dopp ler u ltra- 54. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recom -
sonography as a m easu re of card iac ou tp u t in critically ill ad ults. Inten- binant hu m an activated p rotein C for severe sep sis. N Engl J Med
sive Care Med 2004;30(11):2060–2066. 2001;344(10):699–709.
27. Vincent J, DeBacker D. Pathop hysiology of sep tic shock. Advanced Sep- 55. Vincent JL, Angu s DC, Artigas A, et al. Effects of d rotrecogin alfa (acti-
sis 2001;1:87–92. vated ) on organ d ysfu nction in the PROWESS trial. Crit Care Med
28. Le Blanc L, Lesur O, Valiqu ette L, et al. Role of rou tine blood cu ltures in 2003;31(3):834–840.
d etecting u nap p arent infections d u ring continu ou s renal rep lacem ent 56. Manns BJ, Lee H , Doig CJ, et al. An econom ic evalu ation of activated
therap y. Intensive Care Med 2006;32(11):1802–1807. p rotein C treatm ent for severe sep sis. N Engl J Med 2002;347(13):
29. H eyland D, Cook D, Dod ek P, et al. A rand om ized trial of d iagnostic 993–1000.
techniqu es for ventilator-associated p neu m onia. N Engl J Med 2006; 57. Angu s DC, Lind e-Zw irble WT, Clerm ont G, et al. Cost-effectiveness of
355(25):2619–2630. d rotrecogin alfa (activated ) in the treatm ent of severe sep sis. Crit Care
30. Ticehurst JR, Aird DZ, Dam LM, et al. Effective d etection of toxigenic Med 2003;31(1):1–11.
Clostrid iu m d ifficile by a tw o-step algorithm inclu d ing tests for anti- 58. Lefering R, N eu gebau er EA. Steroid controversy in sep sis and sep tic
gen and cytotoxin. J Clin Microbiol 2006;44(3):1145–1149. shock: a m eta-analysis. Crit Care Med 1995;23(7):1294–1303.
31. Dellinger RP, Levy MM, Carlet JM, et al. Su rviving Sep sis Cam p aign: 59. Bollaert PE, Charp entier C, Levy B, et al. Reversal of late sep tic shock
international guid elines for m anagem ent of severe sepsis and septic w ith su p rap hysiologic d oses of hyd rocortisone. Crit Care Med 1998;
shock: 2008. Crit Care Med 2008;36(1):296–327. 26(4):645–650.
32. Choi PT, Yip G, Qu inonez LG, et al. Crystalloid s vs. colloid s in flu id 60. Annane D, Sebille V, Charp entier C, et al. Effect of treatm ent w ith low
resu scitation: a system atic review. Crit Care Med 1999;27(1):200–210. d oses of hyd rocortisone and flu d rocortisone on m ortality in p atients
33. Schierhou t G, Roberts I. Flu id resu scitation w ith colloid or crystalloid w ith sep tic shock. JAMA 2002;288(7):862–871.
solu tions in critically ill p atients: a system atic review of rand om ised 61. Annane D, Sebille V, Troche G, et al. A 3-level p rognostic classification
trials. BMJ 1998;316(7136):961–964. in septic shock based on cortisol levels and cortisol resp onse to corti-
34. Cook D, Gu yatt G. Colloid u se for flu id resu scitation: evid ence and cotropin. JAMA 2000;283(8):1038–1045.
sp in. Ann Intern Med 2001;135(3):205–208. 62. Annane D, Bellissant E, Bollaert PE, et al. Corticosteroid s in the treat-
35. Dellinger RP. Card iovascu lar m anagem ent of sep tic shock. Crit Care m ent of severe sepsis and septic shock in ad u lts: a system atic review.
Med 2003;31(3):946–955. JAMA 2009;301(22):2362–2375.
36. Martin C, Papazian L, Perrin G, et al. Norepinephrine or dopamine for the 63. Sloane PJ, Gee MH , Gottlieb JE, et al. A m u lticenter registry of p atients
treatment of hyperdynamic septic shock? Chest 1993;103(6):1826–1831. w ith acu te resp iratory d istress synd rom e. Physiology and ou tcom e.
37. Mead ow s D, Ed w ard s JD, Wilkins RG, et al. Reversal of intractable sep- Am Rev Respir Dis 1992;146(2):419–426.
tic shock w ith norep inep hrine therap y. Crit Care Med 1988;16(7): 64. H yers TM. Pred iction of su rvival and m ortality in p atients w ith ad u lt
663–666. resp iratory d istress synd rom e. New Horiz 1993;1(4):466–470.
38. Martin C, Viviand X, Leone M, et al. Effect of norep inephrine on the 65. Luce JM. Acu te lu ng inju ry and the acu te resp iratory d istress syn-
ou tcom e of septic shock. Crit Care Med 2000;28(8):2758–2765. d rom e. Crit Care Med 1998;26(2):369–376.
39. LeDoux D, Astiz ME, Carp ati CM, et al. Effects of p erfu sion p ressu re on 66. Sharm a S, Ku m ar A. Sep tic shock, m u ltip le organ failu re, and acu te res-
tissue p erfu sion in sep tic shock. Crit Care Med 2000;28(8):2729–2732. piratory d istress synd rom e. Curr Opin Pulm Med 2003;9(3):199–209.
40. Van d en Berghe G, d e Zegher F. Anterior p itu itary fu nction d u ring crit- 67. Dreyfu ss D, Basset G, Soler P, et al. In term ittent p ositive-p ressu re
ical illness and d op am ine treatm ent. Crit Care Med 1996;24(9): hyp erven tilation w ith h igh inflation p ressu res p rod u ces p u lm onary
1580–1590. m icrovascu lar inju ry in rats. Am Rev Respir Dis 1985;132(4):880–
41. Land ry DW, Levin H R, Gallant EM, et al. Vasop ressin d eficiency con- 884.
tribu tes to the vasod ilation of sep tic shock. Circulation 1997;95(5): 68. Trem blay L, Valenza F, Ribeiro SP, et al. Inju riou s ventilatory strategies
1122–1125. increase cytokines and c-fos m -RN A expression in an isolated rat lu ng
42. H olm es CL, Patel BM, Ru ssell JA, et al. Physiology of vasop ressin rele- m od el. J Clin Invest 1997;99(5):944–952.
vant to m anagem ent of sep tic shock. Chest 2001;120(3):989–1002. 69. Ranieri VM, Su ter PM, Tortorella C, et al. Effect of m echanical ventila-
43. Sharshar T, Carlier R, Blanchard A, et al. Dep letion of neu rohyp ophy- tion on inflam m atory m ed iators in patients w ith acute respiratory d is-
seal content of vasop ressin in sep tic shock. Crit Care Med 2002;30(3): tress synd rom e: a rand om ized controlled trial. JAMA 1999;282(1):
497–500. 54–61.
44. Reid IA. Role of vasop ressin d eficiency in the vasod ilation of sep tic 70. N ey L, Ku ebler WM. Ventilation w ith low er tid al volu m es as com p ared
shock. Circulation 1997;95(5):1108–1110. w ith trad itional tid al volu m es for acu te lu ng inju ry. N Engl J Med
45. Morales D, Mad igan J, Cu llinane S, et al. Reversal by vasop ressin of 2000;343(11):812–813; au thor rep ly 813–814.
intractable hyp otension in the late p hase of hem orrhagic shock. Circu- 71. Schiffl H , Lang SM, Fischer R. Daily hem od ialysis and the ou tcom e of
lation 1999;100(3):226–229. acu te renal failu re. N Engl J Med 2002;346(5):305–310.
46. Argenziano M, Chou d hri AF, Oz MC, et al. A p rosp ective rand om ized 72. Pinsky MR, Vincent JL, Deviere J, et al. Seru m cytokine levels in hu m an
trial of arginine vasop ressin in the treatm ent of vasod ilatory shock septic shock. Relation to m u ltip le- system organ failu re and m ortality.
after left ventricu lar assist d evice p lacem ent. Circulation 1997;96(9 Chest 1993;103(2):565–575.
Su pp l):II-286–290. 73. Ronco C, Brend olan A, Lonnem ann G, et al. A p ilot stu d y of cou p led
47. Du nser MW, Mayr AJ, Ulm er H , et al. The effects of vasop ressin on sys- p lasm a filtration w ith ad sorp tion in sep tic shock. Crit Care Med 2002;
tem ic hem od ynam ics in catecholam ine-resistant sep tic and postcar- 30(6):1250–1255.
d iotom y shock: a retrosp ective analysis. Anesth Analg 2001;93(1):7–13. 74. John S, Griesbach D, Bau m gartel M, et al. Effects of continu ou s
48. Malay MB, Ashton RC Jr, Land ry DW, et al. Low -d ose vasop ressin in haem ofiltration vs interm ittent haem od ialysis on system ic haem od y-
the treatm ent of vasod ilatory sep tic shock. J Trauma 1999;47(4):699–703; nam ics and splanchnic regional perfusion in septic shock patients: a
d iscu ssion 703–705. p rospective, rand om ized clinical trial. Nephrol Dial Transplant 2001;
49. Ku m ar A, Thota V, Dee L, et al. Tu m or necrosis factor alpha and inter- 16(2):320–327.
leu kin 1beta are resp onsible for in vitro m yocard ial cell d epression 75. Cole L, Bellom o R, H art G, et al. A p hase II rand om ized , controlled trial
ind u ced by hu m an sep tic shock seru m . J Exp Med 1996;183(3):949–958. of continuou s hem ofiltration in sep sis. Crit Care Med 2002;30(1):
50. Parker M, Ognibene F, Parrillo J. Reversible d ep ression of m yocard ial 100–106.
function in septic shock confirm ed by a load -ind epend ent m easure of 76. Reeves JH , Bu tt WW, Shann F, et al. Continu ou s p lasm afiltration in sep -
ventricular perform ance. Clin Res 1990;38:340A. sis synd rom e. Plasm afiltration in Sep sis Stu d y Grou p . Crit Care Med
51. Parker M, Su ffred ini A, N atanson C. Resp onses of left ventricu lar fu nc- 1999;27(10):2096–2104.
tion in su rvivors and nonsu rvivors of sep tic shock. J Crit Care 1989; 77. Esm on CT, Taylor FB Jr, Snow TR. Inflam m ation and coagu lation:
4:19–25. linked processes potentially regulated through a com m on pathw ay
52. Maki DG, Klu ger DM, Crnich CJ. The risk of blood stream infection in m ed iated by p rotein C. Thromb Haemost 1991;66(1):160–165.
ad ults w ith d ifferent intravascu lar d evices: a system atic review of 200 78. Yan SB, Grinnell BW. Recom binant hu m an p rotein C, p rotein S, and
pu blished p rosp ective stu d ies. Mayo Clin Proc 2006;81(9):1159–1171. throm bom od u lin as antithrom botics. Perspectives in Drug Discover and
53. Rivers E, N guyen B, H avstad S, et al. Early goal-d irected therap y in the Design 1993;1:503–520.
treatm ent of severe sep sis and sep tic shock. N Engl J Med 2001; 79. Lam berts SW, Bru ining H A, d e Jong FH . Corticosteroid therap y in
345(19):1368–1377. severe illness. N Engl J Med 1997;337(18):1285–1292.
80. Annane D, Bellissant E, Sebille V, et al. Im p aired p ressor sensitivity to 89. Griffiths RD, Allen KD, And rew s FJ, et al. Infection, m u ltip le organ fail-
norad renaline in sep tic shock patients w ith and w ithou t im paired u re, and su rvival in the intensive care u nit: influ ence of glu tam ine-su p -
ad renal function reserve. Br J Clin Pharmacol 1998;46(6):589–597. p lem ented parenteral nu trition on acqu ired infection. Nutrition
81. Wolfe RR, H ernd on DN , Jahoor F, et al. Effect of severe bu rn injury on 2002;18(7–8):546–552.
su bstrate cycling by glu cose and fatty acid s. N Engl J Med 1987; 90. Gaykem a RP, Dijkstra I, Tild ers FJ. Su bd iap hragm atic vagotom y su p -
317(7):403–408. p resses end otoxin-ind uced activation of hypothalam ic corticotropin-
82. McCow en KC, Malhotra A, Bistrian BR. Stress-ind u ced hyp erglycem ia. releasing horm one neu rons and ACTH secretion. Endocrinology
Crit Care Clin 2001;17(1):107–124. 1995;136(10):4717–4720.
83. van d en Berghe G, Wou ters P, Weekers F, et al. Intensive insu lin therapy 91. Borovikova LV, Ivanova S, Zhang M, et al. Vagu s nerve stim u lation
in the critically ill p atients. N Engl J Med 2001;345(19):1359–1367. attenu ates the system ic inflam m atory resp onse to end otoxin. Nature
84. H eyland DK, Cook DJ, Gu yatt GH . Enteral nu trition in the critically ill 2000;405(6785):458–462.
p atient: a critical review of the evid ence. Intensive Care Med 1993;19(8): 92. Wilson JX, You ng GB. Progress in clinical neu rosciences: sep sis-associ-
435–442. ated encephalop athy: evolving concep ts. Can J Neurol Sci 2003;30(2):
85. H eyland DK. N utritional su p p ort in the critically ill p atients. A critical 98–105.
review of the evid ence. Crit Care Clin 1998;14(3):423–440. 93. Bau e AE, Du rham R, Faist E. System ic inflam m atory resp onse syn-
86. N akad A, Piessevau x H , Marot JC, et al. Is early enteral nu trition in d rom e (SIRS), m u ltiple organ d ysfu nction synd rom e (MODS), m u ltip le
acu te pancreatitis d angerou s? Abou t 20 p atients fed by an end oscop i- organ failu re (MOF): are w e w inning the battle? Shock 1998;10(2):
cally p laced nasogastrojeju nal tu be. Pancreas 1998;17(2):187–193. 79–89.
87. Olah A, Belagyi T, Isseku tz A, et al. Rand om ized clinical trial of sp ecific 94. Knau s WA, Draper EA, Wagner DP, et al. Prognosis in acu te organ-sys-
lactobacillus and fibre su pplem ent to early enteral nu trition in p atients tem failu re. Ann Surg 1985;202(6):685–693.
w ith acute pancreatitis. Br J Surg 2002;89(9):1103–1107. 95. Beal AL, Cerra FB. Mu ltiple organ failu re synd rom e in the 1990s. Sys-
88. Griffiths RD, Jones C, Palm er TE. Six-m onth ou tcom e of critically ill tem ic inflam m atory resp onse and organ d ysfu nction. JAMA 1994;
p atients given glu tam ine-su p p lem ented p arenteral nu trition. Nutrition 271(3):226–233.
1997;13(4):295–302. 96. Wenzel RP. Treating sep sis. N Engl J Med 2002;347(13):966–967.
CHAPTER
16
Hypovolemic Shock
Wendy L. Wahl
■ INTRODUCTION AND ETIOLOGY d iarrhea is often associated w ith hypokalemia and acid osis,
in part d u e to bicarbonate loss (2,3). Eld erly patients w ho
H ypovolem ic shock is a relatively com m on com plication of have received fu ll bow el p reparation before an operation
severe hemorrhage and / or fluid loss in surgical patients. may have significant hypovolemia. GI bleed ing is a special
Shock results from inad equate oxygen d elivery to tissues case w ith a combination of bleed ing and GI tract fluid loss.
and is d epend ent on card iac output, hemoglobin concentra- H ypovolem ia shou ld be consid ered in patients w ith
tion, and arterial oxygen saturation. Card iac output, in turn, melena, coffee-ground emesis, and guaiac positive stool.
d epend s on preload , afterload , and contractility. In hypov- Hypovolemic shock can also exist in states without total
olemic shock, there is inad equate oxygen d elivery d ue to body fluid d epletion and can be divid ed in tw o groups: those
d ecreased intravascular volume or preload . In ad d ition, if with redistribution of the intravascular fluid into the intersti-
hypovolem ic shock is d u e to hem orrhage, there can be a tial or intracellular space and those w ith low preload d ue to
low hem oglobin concentration, w hich fu rther d ecreases increased intravascular capacity. Redistribution may be a
oxygen d elivery. consequence of tissue injury due to trauma or burns, recent
The etiologies of hyp ovolem ic shock can be classified operation, inflammation such as pancreatitis, or anaphylaxis.
into tw o grou ps based on the presence or absence of total While the patient may have increased total bod y fluid, the
bod y flu id d ep letion (Table 16.1). H em orrhage, gastroin- intravascular volume is low leading to hypovolemia. Hypov-
testinal tract (GI), renal, and skin losses are all associated olemia is a very common cause of low urine output in the
w ith total bod y flu id d epletion. In this classification, bleed - first 24 hours after major surgery but is occasionally difficult
ing into the intra-abd om inal, retroperitoneal, or p elvic to d iagnose. Other causes of hypovolemia should be consid -
sp aces or extrem ity fractu re hem orrhage is consid ered a ered, such as bleeding and cardiac dysfunction, especially in
total bod y flu id loss. In an ad ult, significant amou nts of elderly patients who are beyond post-operative day one.
blood can be lost in these cavities w ithou t any external Dru gs and toxins m ay also ind u ce hyp ovolem ic shock
hem orrhage. For exam p le, closed fractures of the fem u r or w ithou t flu id loss from the intravascu lar sp ace by increas-
hip m ay be associated w ith blood loss in excess of a liter (1). ing intravascu lar cap acity. While this is a form of hypov-
Several liters of blood loss in the retrop eritoneu m m ay be olem ic shock, some consid er this grou p a sep arate category
associated w ith p elvic fractu res. Gastrointestinal tract hem - called “d istribu tive shock.” Sep tic shock is d u e to low
orrhage m ay also be extensive before m anifesting sym p - intravascu lar volu m e becau se of flu id red istribu tion and
tom s of hem atem esis, hem atochezia, or m elena. vasod ilatation and is covered in Chap ter 15.
H ypovolemic shock can also occur from ongoing GI
tract losses. From 3 to 6 liters of fluid are secreted by the GI
tract each d ay, w ith most reabsorbed except a small amou nt ■ DIAGNOSIS OF HYPOVOLEMIC SHOCK
lost in the stool. Intractable vom iting, sm all bow el obstru c-
tion, d iarrhea, stomas such as an ileostomy or colostomy, H yp ovolem ic shock rem ains a clinical d iagnosis. Obtaining
and enterocutaneou s fistulae may imp air normal reabsorp- accu rate history is extrem ely im p ortant. A history of thora-
tion. Different sites of GI tract losses are associated w ith coabd om inal trau m a, external bleed ing, long bone or
specific electrolyte d isturbances and can lead to malnutri- p elvic fractu res, GI hem orrhage, vom iting, d iarrhea, lack of
tion. Vomiting can ind uce hypokalemic, hypochloremic, flu id intake, excessive heat, d iu retic u se, excessive thirst or
metabolic alkalosis w ith hypovolemia. Renal compensation p olyu ria m ay aid w ith the d iagnosis and cau se of hypov-
for the hypovolemia is associated w ith reabsorption of olem ic shock. Other etiologies for shock shou ld be consid -
sod ium in exchange w ith hyd rogen and potassium ions ered , esp ecially in p atients w ith recent invasive proced ures
w hich further aggravates electrolyte d isturbances. Severe or trau m a, w here reversible cau ses of shock su ch as tension
p neum othorax or card iac tam ponad e can be tragically m is-
d iagnosed as hyp ovolem ic shock.
Wendy L. Wahl: University of Michigan H ealth System , Know ledge of the body’s physiologic response to shock is
Ann Arbor, MI 48109. required for understanding the symptoms and treatment of
161
Table 1 6 .1 Et iologies of hyp ovolem ic sh ock compensate for decreasing stroke volume. Tachycardia is a
prominent symptom of hypovolemic shock w hen fluid losses
With Total Body Fluid Depletion approach or exceed 15% of intravascular volume.
Hemorrhage
External (Stroke Volu m e) (H eart rate) Card iac ou tp u t (CO)
Internal Ohm ’s law states that a change in p ressu re is d irectly
GI tract hemorrhage p rop ortional to flow and resistance. Therefore, in hypov-
Thoracic, retroperitoneal, pelvic, intra-abdominal bleeding
olem ic p atients w ho have d ecreased card iac ou tp u t (flow ),
Closed long bone fractures
system ic blood pressure m ay be m aintained if there is an
Gastrointestinal tract losses ap p rop riate rise in system ic vascu lar resistance (SVR).
Diarrhea
(CO) (SVR) ∝ (Mean Arterial Pressu re-Central
Fistulae
Venou s Pressu re)
Malabsorption
The increase in SVR is d u e to selective d ecreases in the
Renal Losses
Osmotic diuresis arteriole su p p ly of “nonvital” organs su ch as skin w ith
Diabetes insipidus the goal of m aintaining flow to the vital organs su ch as the
Resolution of acute tubular necrosis brain and heart. As a resu lt, p atients w ith hyp ovolem ic
shock p resent w ith cool and clam m y skin, esp ecially in the
Skin losses
d istal extrem ities.
Open wounds Large flu id losses can also u pset the acid -base balance.
Burns Excessive vom iting m ay be associated w ith hyp ochlorem ic
Without Total Body Fluid Depletion m etabolic alkalosis. Diarrhea or p ancreatic flu id losses m ay
be associated w ith bicarbonate w asting and m etabolic aci-
Redistribution of intravascular fluid to the interstitial or intracellular
space d osis. In hemorrhagic shock, d ecreased oxygen d elivery
shifts the tissues into anaerobic m etabolism lead ing to
Trauma
increased lactic acid p rod u ction and m etabolic acid osis.
Burns Table 16.2 d emonstrates the classic stages of hypov-
Recent operation olem ia (1,4,5). Blood p ressu re is significantly m aintained
Inflammation (pancreatitis, peritonitis) u ntil the later stages of shock. In p reviou sly healthy
p atients, hyp ovolem ia w ith u p to 15% blood volu m e loss is
Anaphylaxis
associated w ith m inim al blood p ressu re changes (1). The
Decreased preload from increased intravascular capacity first notable change in system ic blood p ressu re is a d rop in
(distributive shock) p u lse p ressu re. Increased SVR in resp onse to d ecreased
Toxins p reload p red om inately increases the d iastolic blood pres-
Drugs
sure resu lting in an overall d ecrease in pu lse p ressu re.
GI, Gastrointestinal
Blood volu m e loss beyond 30% is associated w ith m arked
tachycard ia, tachyp nea, mental statu s changes, and a fall in
systolic blood p ressu re. Im m ed iate intervention is required
at this p oint to p revent ischem ic changes and su bsequent
hypovolemic shock. Physical signs of hypovolemic shock are ischem ia-rep erfu sion inju ry w hich w orsen ou tcom es.
due to decreased organ perfusion. Since stroke volume is Trad itionally, urine output has been consid ered a marker
depend ent on preload, afterload, and contractility, a decrease for circulating volume status. In hypovolemic patients, com-
in preload will lead to a lower cardiac output and circulating plex neuroend ocrine responses d ecrease urine volume w hile
volume. This will initiate a cascade of neuroend ocrine increasing urine concentration and reabsorption of sod ium
responses. By increasing the heart rate, the body attempts to and water (6). Hourly urine outputs of 0.5 ml/ kg for adults
Table 1 6 .2 Cla ssifi ca t ion of hyp ovolem ic sh ock

Class I Class II Class III Class IV
Circulating Volume loss% 15 15–30 30–40 40
Heart Rate (beat/min) 100 Tachycardia Tachycardia Marked tachycardia
Pulse Pressure Normal Narrowed Narrowed Unobtainable or very narrow
Systolic Blood Pressure Normal Minimal decrease Decrease Significant decrease
Hourly Urine Output 0.5 cc/Kg 0.5 cc/kg 0.5 cc/kg Minimal
Mental Status Normal Anxious Confused and anxious Markedly depressed or lethargic
Chapter 16 • Hypovolemic Shock 163
and 1 ml/ kg for children are thought to be adequate (7). changes can be late signs of hyp ovolem ia. In ped iatric
While low urine output is seen in hypovolemic shock, it is p atients, hyp otension is a late and om inou s sign (8). There-
not necessarily a specific or sensitive measure. Oliguria is fore, w aiting for hyp otension to occu r is not an option,
also associated w ith septic, cardiogenic, and hepatic shock. since d elayed treatm ent is associated w ith w orse ou tcom es
Oliguria may also be d ue to renal or post renal causes. Low and m u ltisystem organ failu re.
urine output due to urinary tract or catheter obstruction
should be ruled out, as w ell.
The fractional excretion of sod iu m (FEN a ) can be u sefu l
■ TREATMENT
in d istingu ishing renal from p re-renal causes of oligu ria. In shock, the treatm ent goal is to retu rn ad equate tissu e
This calcu lation is based on the concentration of sod iu m p erfu sion rap id ly and safely. In cases of hypovolem ic
(N a) and creatinine (Cr) in both plasm a and urine (8). shock, one of the m ain p roblems is low intravascular vol-
u m e. For su rgical p atients, and p articu larly those w ith
FEN a% [Urine N a][Plasm a Cr]/ [Urine Cr]
trau m atic inju ries, ad equ ate assessm ent of shock requ ires
[Plasm a N a] 100
rap id evalu ation of both airw ay and breathing w ith app ro-
Pre-renal states are associated w ith significant reab- p riate m aneuvers to obtain a secu re airw ay and m aintain
sorp tion of sod iu m lead ing to FEN a less than 1% (9). In con- ad equ ate breathing. After ensu ring the airw ay and breath-
trast, FEN a m ore than 1% is seen in acute tu bu lar necrosis ing are controlled , flu id resu scitation and restoration of
(ATN ), since d am aged tu bu les are not able to absorb volum e status are param ount.
sod iu m . A u rinalysis m ay help d istinguish betw een ATN Sources of hemorrhage need to be controlled . In gastroin-
and hyp ovolem ia. While ATN is associated w ith abnorm al testinal bleeding, this may require upper or low er GI tract
levels of p rotein and cells, the urinalysis is generally nor- end oscopic evaluation w ith maneuvers to stop bleed ing. In
m al in hypovolem ia. H ow ever, presence of ATN d oes not trauma patients w ith active hemorrhage, operative interven-
exclu d e hyp ovolem ia, and they m ay coexist. In ad d ition, tion should not be delayed or postponed for intravenous
FEN a in patients treated w ith d iu retics m ay be inaccurate. (IV) resuscitation (13). Resuscitation should be started on
Conversely, high urine outpu t d oes not exclud e hyp ov- presentation and carried over into the operating room since
olem ia. H yp ovolem ia in the presence of osm otic d iu retics, bleed ing is the most frequent preventable cause of d eath
as seen in hyp erglycem ia, d iabetes insipid us, or acu te alco- after severe injury (14). Operative intervention and control
hol intoxication, m ay be associated w ith norm al or high of hemorrhage are the major interventions for trauma
u rine ou tp u t. Urine ou tp ut d ata shou ld be ju d ged together patients. The timing of fluid resuscitation in penetrating
w ith other clinical find ings. trauma remains controversial. Some authors have suggested
Any d ecrease in glom eru lar filtration rate w ill cau se d elay of IV resuscitation until the bleeding source is und er
blood u rea nitrogen (BUN ) and creatinine to rise. Since cre- control (15,16). Advocates of delayed resuscitation propose
atinine is p rod u ced by skeletal m u scle and is not reab- that aggressive fluid resuscitation in patients w ith uncon-
sorbed by the renal tu bu les, it is m ore representative of trolled bleeding source may increase the blood pressure w ith
renal fu nction than BUN (10). The norm al ratio of BUN to d isruption of natural homeostatic mechanisms such as
plasma creatinine is 10–15 (8). Since there is increased u rea thrombus formation w ith subsequent increased bleeding,
absorp tion w ith hypovolem ia, BUN / creatinine ratios necessitating more resuscitation (17,18). Resuscitation may
above 20 su ggest hypovolem ia (11). evoke a vicious cycle of coagulopathy through d ilution and
consumption of clotting factors w hich worsens hypothermia
from heat loss and administration of cold blood products.
■ Pitfalls in diagnosis A rand om ized clinical trial in H ou ston d em onstrated
Tachycard ia, low pu lse pressure, low blood pressu re, low im p roved su rvival in p enetrating torso p atients w hen flu id
urine ou tp u t, m ental statu s changes, and cold extrem ities resu scitation w as d elayed u ntil op erative intervention (16).
may be som e of the physical signs of hypovolem ic shock. This stu d y involved patients that w ere rap id ly transp orted
H ow ever, there are m any d iagnostic pitfalls in the clinical w ith a fairly short scene-to-op erating room tim e. The find -
assessm ent of hypovolem ic shock (12). Intensive care u nit ings of this stu d y shou ld not be generalized to trau m a
patients m ay have hypovolem ic shock w ith increased p atients in ru ral areas w ith long transp ort tim es, blu nt
interstitial flu id . Distinguishing hypovolem ic shock from m echanism s of inju ry, or p atients w ith head traum a since
card iogenic and septic shock m ay be d ifficu lt, esp ecially in any increase in the length and severity hyp otension m ay
the eld erly. Tachycard ia is a com m on sym ptom of other have significant m orbid ity. While m ost su rgeons agree that
cau ses su ch as p ain, sepsis, and card iogenic shock. The eld - rap id transp ort to trau m a centers shou ld not be d elayed , a
erly and patients w ho u se beta-ad renergic and calcium strategy to w ithhold fluid resuscitation has not been
channel blockers may have norm al heart rates in the pres- ad op ted by m ost centers, and fu rther research is required
ence of hyp ovolem ia (5). Low u rine outpu t m ay be d u e to in this area.
renal or p ost renal cau ses. Conversely, high urine ou tp u t Resuscitation should be initiated w ith large-bore IV
may be d u e to osm otic d iu retics or inability of the kid ney to lines (16-gau ge or larger). While there are no set ru les on
concentrate u rine. As alread y d iscu ssed , blood p ressu re the am ou nt of flu id resu scitation, there are gu id elines. In
the bu rn p op u lation, 2–4 m l of Lactated Ringers is recom - N orm al PCWP is 6–12 m m H g. H ow ever, these valu es
mend ed for each percent of total bod y su rface area (TBSA) are of lim ited u se in the intensive care u nit p atient w ho
bu rn p er kilogram of id eal bod y w eight (7). Therefore, a m ay have increased intrathoracic p ressu re, p ositive p res-
70 kg m an w ho has 30% TBSA burn shou ld receive su re ventilation, abnorm al LV com p liance, and m itral
4200–8400 m l of flu id in the first 24 hou rs after burn inju ry. valve d isease (5). Most intensivists agree that valu es below
H alf of this shou ld be given in the first 8 hours and the rest 10 m m H g are associated w ith low p reload and hyp ov-
in the next 16 hours. These are only guidelines and should olem ia. In fact, in the com p rom ised p atient, increasing
not replace clinical judgment and continuous reassessment PCWP u p to 18 m m H g m ay im p rove card iac ou tp u t
of patients. Burn patients w ith inhalation injury m ay require related to the Frank-Starling cu rve. PCWP and CVP in
significantly more fluid resuscitation. Conversely, a patient p atients w ho have high intrathoracic p ressu re m ay be
w ith clinical signs of ad equate resuscitation may not require p oor p red ictors of LV p reload . Intu bated p atients w ith
all of the fluid recommended in the guideline. Trauma high positive end -expiratory pressure (PEEP 10 cm H 20)
patients are usually given 2-liter fluid challenges. For class p resent a com m on p roblem . Since lu ng stiffness is d ifferent
III and IV hemorrhagic shock, blood transfusion is necessary in each p atient, there is d ifferential transm ission of alveolar
(1). In most patients, sym ptoms of hypovolem ia are seen p ressu re to p u lm onary vessels. There are mu ltip le m ethod s
after at least 10%–15% of intravascular volume has been lost. that have been proposed to calcu late and ad ju st for PEEP in
Therefore, resuscitation with less than 500 ml of isotonic PCWP and CVP m easu rem ents; (24) how ever, none have
fluid in surgical patients is not ad vised . If there is concern been u niform ly accepted .
regarding the potential for congestive heart failure in a sur- Another preload m easu rem ent is right ventricu lar end -
gical patient w ith oliguria, clinical assessment is ind icated . d iastolic volu m e (RVEDV), w hich is m easu red by a m od i-
Recently d ata from com bat casu alties has brou ght atten- fied p u lm onary artery catheter. Mu ltip le stu d ies have
tion to how patients are resuscitated w hen massive d em onstrated RVEDV ind ex to be su p erior to PCWP in car-
amou nts of blood (packed red blood cells or PRBCs) are d iac p reload m easu rem ent, esp ecially in p atients w ith
required . In patients w ith ongoing bleed ing and at high risk increased thoracic p ressu re (25,26). At higher PEEP valu es,
for d eveloping the lethal triad of hypothermia, acid osis, and card iac ind ex correlates significantly better w ith RVEDV
coagulopathy, military d ata supports the use of fresh frozen ind ex than PCWP or CVP (27,28). The op tim u m RVEDV
plasma (FFP) w ith PRBCs transfused at a ratio of 1:1 or 1:2 ind ex range is betw een 80 and 160 m L/ m 2 w ith m eans in
PRBC:FFP (19–21). For patients w ho received over 6 u nits of the 120 to 140 m L/ m 2 range (28).
PRBC, low er ratios (higher use of FFP) w ere associated w ith While p u lm onary artery catheter u se is an established
im proved m ortality rates. These results are not p rosp ective techniqu e in su rgical intensive care u nits, there are no ran-
or rand omized , and not all civilian centers have supported d om ized , p rosp ective stu d ies w hich d em onstrate benefit.
this view point (22,23). The most important point of the Pulm onary artery catheters should be only used as an
resuscitation may be for the clinician to institute early use of ad ju nct to a thorou gh clinical assessm ent. Ind iscrim inate or
FFP, in ad d ition to platelets, in patients requiring mu ltiple inappropriate u se of pulm onary artery catheters m ay be
PRBC transfusions in a short period of time. The goal is to associated w ith comp lications w ithou t significant benefit
minimize the risk of w orsening coagulopathy caused by to the p atient (29–31). Intensive care u nit sp ecialists are
further d ilution and consumption of clotting factors. continu ou sly looking for m ore accu rate or less invasive
m ethod s of m easu ring intravascu lar volu m e statu s su ch as
■ MONITORING AND ENDPOINTS OF esop hageal Dop p ler monitoring. In this techniqu e a sm all-
caliber Dop p ler u ltrasou nd is p laced in the esop hagu s via
RESUSCITATION
an oral or nasal rou te, m easu ring Dop p ler w aveform s to
Occasionally there is a need for a d irect measurement of car- estim ate p reload and card iac fu nction (32). While som e of
d iac preload or left ventricular (LV) filling pressure. The these new er m ethod s have show n p rom ise, m ore stud ies
goal is to estimate the LV end -d iastolic pressure (LVEDP). are need ed to d efine their efficacy and lim itations.
The most commonly used measures of preload are central The u ltim ate end point for flu id resu scitation is ad equate
venous pressure (CVP), d etermined by a central venous tissu e p erfu sion. Many clinical ind icators have been used ,
catheter, and pulmonary capillary w ed ge pressure (PCWP), su ch as resolution of tachycard ia, acid osis, and improved
measured by pulmonary artery catheter. PCWP is measured mental status, extremity perfusion, and urine output. The
by inflating a balloon in the p ulmonary artery and creating primary end point in critically ill patients w ho have p ul-
a continuous column of blood to the left atrium. PCWP monary artery catheters remains elusive. Some stud ies
reflects left atrial pressure, w hich is an approximation of regard ing optimal values of card iac ind ex, mixed oxygen
LVEDP. CVP is a m easu re of right atrial p ressure w hich esti- venou s satu ration, and oxygen d elivery ind ex (33,34) have
mates right ventricle end d iastolic pressure. CVP is, there- d emonstrated that critically injured patients w ho achieved
fore, a poor pred ictor of LVEDP, especially in patients w ith a su pranormal oxygen d elivery ind ex of 600 ml/ min/ m 2
increased pu lm onary artery resistance, chronic obstructive had higher survival rates (35). H ow ever, further stud ies d id
pulmonary d isease, right heart failu re and valvu lar d ys- not support a supranormal oxygen d elivery ind ex as an
function. end p oint for resu scitation (33). The end p oint for flu id
resu scitation rem ains a clinical ju d gm ent that m ay be after inju ry d id not show any m easu rable benefit for those
guid ed by physiological parameters, laboratory valu es such w ho received leu kored u ced PRBCs (48).
as p H , pu lmonary artery catheter values such as oxygen Prosp ective, rand om ized stu d ies have d em onstrated
d elivery ind ex and mixed venous oxygen saturation, and that restrictive strategies for red -cell transfu sion (hem oglo-
resolution of acid osis. bin concentration maintained at 7.0 to 9.0 g per d eciliter)
N ew er, less invasive d evices to aid in d eterm ining m ay be su p erior to a liberal transfu sion strategy (hem oglo-
w hether patients have been ad equately resuscitated inclu d e bin concentration m aintained at 10.0 to 12.0 g per d eciliter)
monitors w hich m easure m uscle (Pm O 2) and soft tissu e in critically ill p atients, w ith the p ossible exception of
oxygenation (StO 2) and perfu sion (36–38). Low valu es p atients w ith acu te m yocard ial infarction and u nstable
early in the resuscitation phase of traum a app ear to be angina (49). Use of other blood p rod u cts su ch as FFP is
associated w ith increased risk for infectiou s comp lications ind icated for coagu lation factor d eficiencies. Using FFP for
or organ failu re (39). Som e authors feel that these d evices resu scitation w ithou t evid ence of coagu lation factor d efi-
m ay id entify u nrecognized malp erfu sion in p atients w ho ciency is controversial (50).
otherw ise ap p ear resu scitated . It d oes app ear that sim p ler Theoretically, u se of colloid s in resu scitation of hypov-
param eters su ch as base d eficit on arterial blood gas m eas- olem ic p atients is associated w ith p reservation of p lasm a
u rem ents are strongly correlated w ith Pm O 2, and the over- osm otic p ressu re, m ore efficient p lasm a volu m e expansion,
all benefit for these d evices is still und er investigation (39). and d ecreased tissu e and p u lm onary ed em a. H ow ever,
clinical stu d ies have not d em onstrated a significant
im provem ent in patient outcom es w ith colloid resu scita-
■ Choice of resuscitation fluid tion (51,52). The three com m only u sed colloid s are albu -
The choice of flu id resu scitation has becom e one of the m in, H etastarch, and Dextran-70. The u se of Dextran-70
most controversial topics in critical care. There are three has been lim ited d ue to its association w ith anaphylactic
basic choices: blood and blood prod ucts, colloid s, and crys- reaction and antithrom botic effect (53). Album in is the
talloid s. Blood su bstitutes are not currently available and m ajor colloid flu id u sed in the United States. In ad d ition to
are not d iscu ssed . its colloid al effect, albu m in has been p rom oted as a free
Red cell transfu sion to norm alize blood cou nts offers rad ical and toxin scavenger. Resu scitation w ith 25% albu-
several theoretical ad vantages. Increased hem oglobin con- m in attenu ates lu ng inju ry in rat m od els, in p art d u e to its
centration m ay increase oxygen cap acity and increase oxy- antioxid ant p rop erty (54). N evertheless, there have been
gen d elivery to the tissu e. Red blood cell transfu sions are several clinical stu d ies that have not d em onstrated any
an efficient m ethod of resu scitation, since red cells w ill beneficial effect in u sing albu m in (54,55,56). A Cochrane
m ostly rem ain in the intravascu lar sp ace. In p atients w ith Grou p m eta analysis com p aring albu m in to crystalloid
active bleed ing, blood cell transfu sion is ap p rop riate. resu scitation fou nd increased m ortality associated w ith
There is a d ebate regard ing blood cell transfu sion in the albu m in u se (57). The heterogeneou s p opu lation of
critically ill p atient w ithou t an active sou rce of hem or- p atients u sed in this m eta analysis is a significant lim itation
rhage. In stable critically ill p atients, PRBC transfu sion has (52). H ow ever, a p rosp ective stu d y by the SAFE investiga-
been associated w ith increased infections and m ortality tors w ith alm ost 7,000 ICU p atients, failed to d em onstrate a
and is not recom m end ed (40,41). Other p roblem s w ith benefit of resu scitation w ith the u se of 4% albu m in solution
blood resu scitation stem from the age and storage tim e of com p ared to norm al saline (58).
the blood p rod u ct. Stored , refrigerated blood d oes not Crystalloid s have been the m ainstay for treatm ent of
have the sam e p otential to im p rove oxygen carrying hyp ovolem ia. A nu m ber of solu tions are available w ith
cap acity as fresh, w hole blood . If available, there is no norm al saline and lactated Ringers solution being the m ost
qu estion that au tologou s fresh blood is the best resu scita- com m only u sed . N orm al saline (0.9% N aCl) has 154 m Eq
tion flu id . H ow ever, in m ost civilian settings, the available of both sod iu m and chlorid e and slightly higher osm olarity
red blood cell su p p ly is neither au tologou s nor fresh. Stor- than p lasm a. Ad m inistration of large volu m es of norm al
age of blood im p airs red blood cell d eform ability and flow saline m ay ind u ce hyp erchlorem ic nonanion gap acid osis,
in the m icrocircu lation (42). This p artially exp lains the w hich has lim ited the u se of this solu tion (59).
find ings from m u ltip le stu d ies that red blood cell transfu - H yp ertonic saline resu scitation (7.5% N aCl) has been
sion d oes not im p rove tissu e hyp oxia (42–46). In ad d ition, p rom oted for its efficient intravascu lar volu m e resuscita-
it is w ell know n that allogeneic blood transfu sion is tion, rap id restoration of blood p ressu re and card iac outpu t
im m u nosu p p ressive. Blood transfu sions w ere u sed in the w ith improved cerebral perfusion, and potential for exp and -
p ast to increase su ccess rates for renal transp lantation. ing circu lating volu m e by re-absorption of fluid from inter-
Blood transfu sions are associated w ith increased rates of stitial sp ace (60,61). H yp ertonic saline m ay d ecrease the
cancer recu rrence and nosocom ial infection (40,41,47). required volum e resu scitation w ith d ecreased tissu e ed em a.
Som e believe that the resid u al leu kocytes p resent in the This w as thou ght to be beneficial in trau m a p atients, espe-
allogeneic blood p rod u cts are p artly resp onsible for this cially those w ith head inju ries (62). Original stu d ies
im m u nom od u latory effect. H ow ever, a recent stu d y in d em onstrated the safety of hyp ertonic saline resu scitation
trau m a p atients receiving PRBCs w ithin the first 24 hou rs w ith a trend of im p roved ou tcom es of head inju ry p atients
or p atients requ iring su rgery (63,64). More recently, hyp er- 3. Sack DA, Sack RB, N air GB, et al. Cholera. Lancet 2004;363(9404):
223–233.
tonic saline has been show n to be a flu id w ith significant 4. Bu chm an TG, Jacobsohn E. Shock. In: Greenfield LJ, Mu lholland MW,
mod ulation of system ic inflam m atory response to rep erfu- Old ham KT, Zelenock GB, Lillem oe KD, ed s. Surgery: Scientific principle
sion inju ry, w hich m ay be beneficial in patients w ith shock and practice. Philad elphia, PA: Lip p incott William s & Wilkins; 2001:
202–217.
(65). Early hyp ertonic saline ad m inistration m ay attenu ate 5. Groeneveld ABJ. H ypovolem ic shock. In: Parrillo JE, Dellinger RP, ed s.
innate imm u ne resp onse to injury, such as m acrop hage, Critical care medicine, 2nd ed . St. Lou is, MO: Mosby; 2002:465–500.
neu trop hil, and end othelial cell activation, and d ecrease 6. Rose B, Post TW. Clinical physiology of acid-base and electrolyte disorders.
N ew York, N Y: McGraw -H ill; 2001.
the risk of fu tu re organ d ysfunction synd rom e (66–68). 7. Am erican Bu rn Association. Advance Burn Life Support Course: Provider
Clinical trials to evalu ate the ou tcom e for patients in manual. Chicago: Am erican Bu rn Association; 2001.
shock follow ing blu nt traum atic inju ry, rand om ized to 8. Magnu son DK. N eonatal and p ed iatric p hysiology. In: Greenfield LJ,
Mu lholland MW, Old ham KT, Zelenock GB, Lillem oe KD, ed s. Surgery:
receive 250 m l of 7.5% hypertonic saline/ 6% d extran fol- Scientific principle and practice, 3rd ed . Philad elp hia, PA: Lip p incott
low ed by lactated Ringers versu s lactated Ringers alone, William s & Wilkins; 2001:1901–1931.
w ere recently su sp end ed d u e to lack of d em onstrable 9. Miller TR, And erson RJ, Linas SL, et al. Urinary d iagnostic ind ices in
acute renal failu re: a prosp ective stu d y. Ann Intern Med 1978;89(1):
im proved outcom es d espite positive resu lts in anim al 47–50.
mod els (69). Cu rrently, hypertonic saline is not rou tinely 10. Clinical manifestations and diagnosis of volume depletion. Post TW, Rose
used and fu rther research is ongoing in isolated head BD. Available at: http:/ / w w w.u td ol.com / ap p lication/ top ic.asp ?file
c_neph/ 6291&typ e A&selected Title 2 19. Up toDate Online 18.2
injury p atients to d efine the tim ing, am ou nt, and if this accessed N ovem ber 22, 2010.
trau m a su bp op u lation m ay benefit from hyp ertonic saline 11. Dossetor JB. Creatininem ia versu s u rem ia. The relative significance of
resuscitation (70). blood urea nitrogen and seru m creatinine concentrations in azotem ia.
Ann Intern Med 1966;65(6):1287–1299.
Lactated Ringers is the solution used by most surgeons 12. Cohn JN. Blood pressure measurement in shock. Mechanism of inaccu-
for resuscitation of hypovolemic patients. Lactated Ringers racy in ausculatory and palpatory methods. JAMA 1967;199(13):118–122.
is physiologically balanced with similar electrolyte concen- 13. Baskett PJ. ABC of m ajor traum a. Managem ent of hyp ovolaem ic shock.
BMJ 1990;300(6737):1453–1457.
trations as plasma w ith 130 mEq N a , 4 mEq K , 3 mEq 14. Sau aia A, Moore FA, Moore EE, et al. Ep id em iology of trau m a d eaths: a
Ca , 109 mEq Cl , and 28 mEq of HCO 3 per liter. Due to reassessm ent. J Trauma 1995;38:185–193.
the presence of potassium , lactated Ringers should not be 15. Cap one AC, Safar P, Stezoski W, et al. Im p roved ou tcom e w ith flu id
restriction in treatm ent of u ncontrolled hem orrhagic shock. J Am Coll
given to patients w ith hyperkalemia or renal failure. Lac- Surg 1995;180:49–56.
tated Ringers has been routinely used for massive resuscita- 16. Bickell WH , Wall MJ Jr, Pep e PE, et al. Im m ed iate versu s d elayed flu id
tion for trauma and burn patients. H ow ever, recent stud ies resuscitation for hyp otensive patients w ith p enetrating torso injuries.
N Engl J Med 1994;331(17):1105–1109.
have d emonstrated a potential association betw een lactated 17. Silbergleit R, Satz W, McN am ara RM, et al. Effect of p erm issive
Ringers resuscitation and modulation of leukocyte function hyp otension in continu ou s u ncontrolled intra-abd om inal hem orrhage.
(71,72). Most commercially available lactated Ringers is a Acad Emerg Med 1996;3(10):922–926.
18. Solom onov E, H irsh M, Yahiya A, et al. The effect of vigorou s flu id
racemic mixture of D and L stereoisomers. While the L iso- resuscitation in uncontrolled hem orrhagic shock after m assive splenic
mer is associated w ith low toxicity, the D isomer, w hich is inju ry. Crit Care Med 2000;28(3):749–754.
normally only produced by gastrointestinal flora, has been 19. H olcom b JB, Jenkins D, Rhee P, et al. Dam age control resu scitation:
d irectly ad d ressing the early coagu lop athy of trau m a. J Trauma 2007;
associated with clinical toxicity and potentially harmful 62:307–310.
changes in leukocyte function (71,73). Further studies of the 20. Gonzalez EA, Moore FA, H olcom b JB, et al. Fresh frozen p lasm a shou ld
effect of lactated Ringers resuscitation in surgical patients are be given earlier to p atients requ iring m assive transfu sion. J Trauma
2007;62:112–119.
in progress. Meanw hile, lactated Ringers remains a clinically 21. Borgm an MA, Spinella PC, Perkins JG, et al. The ratio of blood p rod -
acceptable solution for resuscitation of surgical patients. u cts transfu sed in p atients receiving m assive transfu sions at com bat
sup p ort hospitals. J Trauma 2007;63:805–813.
22. Gajic O, Rana R, Winters JL, et al. Transfu sion-related acu te lu ng inju ry
■ SUMMARY in the critically ill. Am J Respir Crit Care Med 2007;176:88–91.
23. Kashuk JL, Morre EE, Johnson JL, et al. Post-inju ry life threatening
H yp ovolem ic shock remains a com mon entity in surgical coagulop athy: is 1:1 fresh frozen p lasm a p acked red blood cells the
answ er? J Trauma 2008;65(2):261–270.
patients. Early recognition and prom p t resu scitation are 24. Tebou l JL, Pinsky MR, Mercat A, et al. Estim ating card iac filling p res-
the m ajor cornerstones for positive outcom es. Restoration sure in m echanically ventilated p atients w ith hyp erinflation. Crit Care
of circu lating volu m e, d epend ent on the etiology of flu id Med 2000;28(11):3631–3636.
25. Diebel LN , Myers T, Dulchavsky S. Effects of increasing airw ay p res-
loss, is cru cial. Stabilization of the patient m ay requ ire air- su re and PEEP on the assessm ent of card iac p reload . J Trauma 1997;
w ay control to allow for ad equate fluid replacem ent. Atten- 42(4):585–590; d iscu ssion 590–581.
tion to acid -base, electrolyte, and coagulation abnorm alities 26. Lu ecke T, Roth H , H errm ann P, et al. Assessm ent of card iac p reload
and left ventricu lar fu nction und er increasing levels of positive end -
is also central to su ccessfu l resu scitation from hypovolem ic exp iratory pressu re. Intensive Care Med 2004;30(1):119–126.
shock. 27. Cheatham ML, N elson LD, Chang MC, et al. Right ventricu lar end -
d iastolic volu m e ind ex as a p red ictor of p reload statu s in p atients on
positive end -expiratory pressu re. Crit Care Med 1998;26(11):1801–1806.
■ REFERENCES 28. Du rham R, N eu naber K, Vogler G, et al. Right ventricu lar end -d iastolic
volu m e as a m easure of preload . J Trauma 1995;39(2):218–223; d iscu s-
1. Am erican College of Su rgeons. Advanced Trauma Life Support: instructor sion 223–214.
manual. 6th ed . Chicago: Am erican College of Su rgeons; 1997. 29. Sand ham JD, H ull RD, Brant RF, et al. A rand om ized , controlled trial of
2. Assad i F, Cop elovitch L. Sim p lified treatm ent strategies to flu id ther- the u se of p u lm onary-artery catheters in high-risk su rgical p atients.
ap y in d iarrhea. Pediatr Nephrol 2003;18(11):1152–1156. N Engl J Med 2003;348(1):5–14.
30. Bernard GR, Sopko G, Cerra F, et al. Pu lm onary artery catheterization 52. Bold t J. The good , the bad , and the u gly: shou ld w e com p letely banish
and clinical outcom es: N ational H eart, Lu ng, and Blood Institu te and hum an albu m in from our intensive care units? Anesth Analg 2000;
Food and Dru g Ad m inistration Workshop Rep ort. Consensu s State- 91(4):887–895.
m ent. JAMA 2000;283(19):2568–2572. 53. Waters LM, Christensen MA, Sato RM. H etastarch: an alternative col-
31. Robin ED. The cu lt of the Sw an-Ganz catheter. Overu se and abu se of loid in bu rn shock m anagem ent. J Emerg Nurs 1990;16(4):279–287.
pu lm onary flow catheters. Ann Intern Med 1985;103(3):445–449. 54. Pow ers KA, Kap u s A, Khad aroo RG, et al. Tw enty-five p ercent albu m in
32. Seou d i H M, Perkal MF, H anrahan A, et al. The esop hageal Dop p ler p revents lu ng inju ry follow ing shock/ resu scitation. Crit Care Med
m onitor in m echanically ventilated surgical patients: d oes it w ork? 2003;31(9):2355–2363.
J Trauma 2003;55(4):720–725; d iscu ssion 725–726. 55. Fergu son N D, Stew art TE, Etchells EE. H u m an albu m in ad m inistration
33. Velm ahos GC, Dem etriad es D, Shoem aker WC, et al. End p oints of in critically ill patients. Intensive Care Med 1999;25(3):323–325.
resu scitation of critically inju red patients: norm al or supranorm al? A 56. Schierhou t G, Roberts I. Flu id resu scitation w ith colloid or crystalloid
prospective rand om ized trial. Ann Surg 2000;232(3):409–418. solu tions in critically ill p atients: a system atic review of rand om ised
34. McKinley BA, Kozar RA, Cocanou r CS, et al. N orm al versu s su p ranor- trials. BMJ 1998;316(7136):961–964.
m al oxygen d elivery goals in shock resuscitation: the response is the 57. Cochrane Inju ries Grou p Albu m in Review ers. H u m an albu m in ad m in-
sam e. J Trauma 2002;53(5):825–832. istration in critically ill p atients: system atic review of rand om ised con-
35. Shoem aker WC. Monitoring and therap y for you ng trau m a p atients. trolled trials. BMJ 1998;317(7153):235–240.
Crit Care Med 1994;22(4):548–549. 58. The SAFE Stu d y Investigators. A com p arison of albu m in and saline for
36. Waxm an K, Annas C, Dau ghters K, et al. A m ethod to d eterm ine the flu id resuscitation in the intensive care u nit. N Engl J Med 2004;350:
ad equ acy of resuscitation u sing tissu e oxygen m onitoring. J Trauma 2247–2256.
1994;36:852–858. 59. Waters JH , Gottlieb A, Schoenw ald P, et al. N orm al saline versu s lac-
37. Drucker W, Pearce F, Glass-H eid enreich L, et al. Su bcu taneou s tissu e tated Ringer ’s solu tion for intraop erative flu id m anagem ent in p atients
oxygen pressu re: a reliable ind ex of perip heral perfusion in hum ans u nd ergoing abd om inal aortic aneurysm repair: an outcom e stu d y.
after injury. J Trauma 1996;40(Su p p l):S116–S122. Anesth Analg 2001;93(4):817–822.
38. Knud son MM, Berm u d ez KM, Doyle CA, et al. Use of tissu e oxygen 60. Rocha-e-Silva M, N egraes GA, Soares AM, et al. H yp ertonic resu scita-
tension m easurem ents d u ring resu scitation from hem orrhagic shock. tion from severe hem orrhagic shock: p atterns of regional circu lation.
J Trauma 1997;42:608–614. Circ Shock 1986;19(2):165–175.
39. Ikossi DG, Knu d son MM, Morabito DJ, et al. Continu ou s m uscle tissu e 61. Gem m a M, Cozzi S, Piccoli S, et al. H yp ertonic saline flu id therap y fol-
oxygenation in critically inju red patients: a p rospective observational low ing brain stem trau m a. J Neurosurg Anesthesiol 1996;8(2):137–141.
stu d y. J Trauma 2006;61:780–790. 62. You ng WF, Rosenw asser RH , Vasthare US, et al. Preservation of p ost-
40. Taylor RW, Manganaro L, O’Brien J, et al. Im p act of allogenic packed com p ression spinal cord fu nction by infu sion of hyp ertonic saline.
red blood cell transfu sion on nosocom ial infection rates in the critically J Neurosurg Anesthesiol 1994;6(2):122–127.
ill p atient. Crit Care Med 2002;30(10):2249–2254. 63. Vassar MJ, Perry CA, Gannaw ay WL, et al. 7.5% sod iu m chlorid e/
41. Gazm u ri RJ, Shakeri SA. Blood transfu sion and the risk of nosocom ial d extran for resu scitation of trau m a p atients u nd ergoing helicop ter
infection: an und erreported com plication? Crit Care Med 2002;30(10): transp ort. Arch Surg 1991;126(9):1065–1072.
2389–2391. 64. Mattox KL, Maningas PA, Moore EE, et al. Prehosp ital hyp ertonic
42. McCrossan L, Masterson G. Blood transfu sion in critical illness. Br J saline/ d extran infu sion for p ost-trau m atic hyp otension. The U. S. A.
Anaesth 2002;88(1):6–9. Mu lticenter Trial. Ann Surg 1991;213(5):482–491.
43. Steffes CP, Bend er JS, Levison MA. Blood transfu sion and oxygen con- 65. Ju nger WG, Coim bra R, Liu FC, et al. H yp ertonic saline resu scitation: a
su m p tion in su rgical sep sis. Crit Care Med 1991;19(4):512–517. tool to m od u late im m u ne fu nction in trau m a p atients? Shock 1997;8(4):
44. Marik PE, Sibbald WJ. Effect of stored -blood transfu sion on oxygen 235–241.
d elivery in patients w ith sep sis. JAMA 1993;269(23):3024–3029. 66. Coim bra R, H oyt DB, Ju nger WG, et al. H yp ertonic saline resu scitation
45. Lorente JA, Land in L, De Pablo R, et al. Effects of blood transfu sion on d ecreases su scep tibility to sep sis after hem orrhagic shock. J Trauma
oxygen transport variables in severe sep sis. Crit Care Med 1993;21(9): 1997;42(4):602–606; d iscu ssion 606–607.
1312–1318. 67. Arbabi S, Rosengart MR, Garcia I, et al. H yp ertonic saline solu tion
46. Conrad SA, Dietrich KA, H ebert CA, et al. Effect of red cell transfu sion ind uces prostacyclin p rod u ction by increasing cyclooxygenase-2
on oxygen consum ption follow ing fluid resuscitation in septic shock. expression. Surgery 2000;128(2):198–205.
Circ Shock 1990;31(4):419–429. 68. Cuschieri J, Gou rlay D, Garcia I, et al. H yp ertonic p recond itioning
47. Blu m berg N, Heal JM. Im m unom od u lation by blood transfu sion: an inhibits m acrophage resp onsiveness to end otoxin. J Immunol 2002;
evolving scientific and clinical challenge. Am J Med 1996;101(3):299–308. 168(3):1389–1396.
48. Watkins TR, Rubenfeld GD, Martin TR, et al. Effects of leu kored u ced 69. New analysis of halted trial of hypertonic saline for patients in traumatic
blood on acu te lung inju ry after trau m a: a rand om ized controlled trial. shock. Barclay L; 2009. Available at: http :/ / w w w.m ed scap e.com /
Crit Care Med 2008;36:1493–1499. view article/ 590647. Accessed May 07, 2009.
49. H ebert PC, Wells G, Blajchm an MA, et al. A m u lticenter, rand om ized , 70. Pru itt BA Jr. Does hyp ertonic bu rn resu scitation m ake a d ifference? Crit
controlled clinical trial of transfusion requ irem ents in critical care. Care Med 2000;28(1):277–278.
Transfusion Requ irem ents in Critical Care Investigators, Canad ian 71. Kou stova E, Stanton K, Gu shchin V, et al. Effects of lactated Ringer ’s
Critical Care Trials Grou p . N Engl J Med 1999;340(6):409–417. solu tions on hu m an leu kocytes. J Trauma 2002;52(5):872–878.
50. Contreras M, Ala FA, Greaves M, et al. Gu id elines for the u se of fresh 72. Kou stova E, Rhee P, H ancock T, et al. Ketone and p yru vate Ringer ’s
frozen plasm a. British Com m ittee for Stand ard s in H aem atology, solutions d ecrease pulm onary apoptosis in a rat m od el of severe hem -
Working Party of the Blood Transfu sion Task Force. Transfus Med 1992; orrhagic shock and resu scitation. Surgery 2003;134(2):267–274.
2(1):57–63. 73. Veech RL, Fow ler RC. Cerebral d ysfu nction and resp iratory alkalosis
51. Tranbau gh RF, Lew is FR. Crystalloid versu s colloid for fluid resu scita- d uring p eritoneal d ialysis w ith D-lactate-containing d ialysis flu id s. Am
tion of hyp ovolem ic p atients. Adv Shock Res 1983;9:203–216. J Med 1987;82(3):572–574.
CHAPTER
17
Fluid and Electrolyte Abnormalities

Bradley D. Freeman
■ INTRODUCTION rou ghly 10% of total bod y w ater or 25% of the extracellular
flu id space) and an extravascular or interstitial com p art-
Intravenous flu id therapy is integral to the practice of su r- ment (rou ghly 30% of the total bod y w ater or 75% of the
gery. For m any p atients, su ch as those u nd ergoing m inor extracellu lar flu id sp ace). Su rgeons sp eak frequ ently of
p roced ures or requiring parenteral hyd ration for only brief “third sp ace” flu id losses or “flu id third sp acing.” The third
p eriod s, intravenou s flu id prescription is u ncom plicated . flu id space is extracellu lar flu id that is neither intravascu lar
In contrast, for p atients w ho have und ergone com p lex nor interstitial and is not im m ed iately p hysiologically con-
operations, su stained m ajor traum a, or possess significant nected to these com p artm ents. This third flu id sp ace repre-
com orbid ities, m eticu lous attention to fluid therap y is sents a p atient’s nonsp ecific resp onse to acu te insu lt, from
essential to avoid seriou s electrolyte d isturbance and other su rgery, infection, or trau m a. The m agnitu d e and d u ration
ad verse sequ elae. Fu rther, because of the su bstantial range of third sp ace flu id accu m u lation is d irectly p rop ortional to
of acqu isition costs of cu rrently available intravenou s flu id the d egree of the inciting insu lt and the tim e requ ired for its
p reparations, cou p led w ith an environm ent increasingly resolu tion. Third sp ace flu id accu m u lation m u st be taken
focused on cost containm ent, econom ic consid erations are into account w hen prescribing intravenous fluid s either for
becom ing a greater part of su rgical d ecision-m aking in this maintenance therapy or for resu scitation.
area. A com p rehensive d iscussion of fluid and electrolyte
m anagem ent is beyond the scop e of this text. Rather, the
p urpose of this chapter is to focus on basic asp ects of flu id ■ Crystalloids
m anagem ent, d iscu ss potential com plications and elec-
Types of Crystalloid Solutions
trolyte d erangem ents associated w ith comm only u sed
intravenou s flu id s, and review recent literatu re exam ining Commonly used intravenous fluid s are d erived from tw o
the relative risks and benefits of selected therapies. The categories, crystalloid s and colloid s. Crystalloid s contain
u ltim ate goal of this analysis is to prom ote an ap proach to sod ium as their osm otically active p article and d istribute
intravenou s flu id m anagem ent that is evid ence-based and throu ghou t the extracellu lar space, such that 25% to 30% of
cost-effective. the infu sed volu m e rem ains in the intravascu lar com part-
ment (1). The pred ominant effect of crystalloid ad ministra-
tion is to expand the interstitial, not the intravascular, sp ace
■ Fluid compartments (2). While a variety of crystalloid solutions are available, the
Know led ge of bod y flu id com partm ent d istribu tion is p rototypes are 0.9% N aCl (normal saline) and lactated
essential both for u nd erstand ing the p hysiological changes Ringer ’s solution. N orm al saline contains N a and Cl at
that occu r follow ing su rgery or injury, and to gu id e intra- concentrations slightly greater than those found in plasma;
venou s flu id u se. Total bod y w ater equ als rou ghly 60% of lactated Ringer ’s solution contains these constituents as
lean bod y w eight, is slightly higher in m en, is m ost concen- w ell as K , Ca 2 , and a H CO 3 source at near physiologic
trated in skeletal m u scle, and d eclines w ith age. Total bod y levels. With m inor excep tions, 0.9% N aCl and lactated
w ater can be d ivid ed into tw o m ajor com partm ents: an Ringer ’s solu tion can be used interchangeably, and few
intracellu lar flu id com partm ent, comp rising 60% of the complications are specifically associated w ith these formu-
total bod y w ater com partm ent (or 40% of lean bod y lations. Lactated Ringer ’s solu tion shou ld not be used in
w eight), and an extracellular flu id com partm ent, com p ris- patients w ith hyperkalemia. Further, the Ca 2 p resent in
ing 40% of the total bod y w ater com partm ent (or 20% of lactated Ringer ’s can bind certain d ru gs, d im inishing
lean bod y w eight). The extracellu lar flu id space is fu rther bioavailability, as w ell as chelate citrate present in packed
subd ivid ed into an intravascular com partm ent (equaling red blood cells, prom oting coagu lation (2). For this reason,
lactated Ringer ’s solution is contraind icated as a d ilu ent for
blood (2). The lactate present in lactated Ringer ’s solution
Bradley D. Freeman: Dep artm ent of Su rgery, Washington d oes not interfere w ith seru m lactate measurements (1).
University School of Med icine St. Lou is, MO. Most commonly used crystalloid solutions are derivatives
168
Chapter 17 • Fluid and Electrolyte Abnormalities 169
of either lactated Ringers solution or 0.9% N aCl (e.g., em p tying, stu d ied on the fou rth p ostop erative d ay, w as
D 5/ 0.45% N aCl, D 5/ lactated Ringer ’s, etc.). significantly d elayed in patients receiving stand ard flu id
Dextrose is a comm on ad d itive to crystalloid s. The orig- therap y, com p ared w ith that in p atients m anaged w ith
inal intent of incorporating d extrose into intravenous flu - flu id restriction. Likew ise, p atients receiving stand ard fluid
id s w as to p rovid e a source of nonprotein calories, thu s therapy had slow er resolu tion of ileu s and longer hospital
potentially d im inishing protein catabolism . A 5% d extrose stays. The m echanism u nd erlying these find ings is u nclear
solu tion p rovid es app roxim ately 170 kcal/ L. While the but attributed to the possible d evelopm ent of bow el w all
clinical benefit of this p rotein sp aring effect is u np roven, ed em a second ary to hyp oalbu m inem ia or sod iu m excess.
the u se of d extrose-containing fluid s is essential in the peri- Sim ilarly, in a p rosp ective m u lticenter stu d y, patients
op erative m anagement of fasting d iabetics to d ecrease the u nd ergoing elective colon resection and rand om ized to a
likelihood of ketosis (3). These solutions are likew ise u sefu l restricted intravenous flu id regim en d esigned to m aintain
as a sou rce free w ater replacem ent in patients unable to tol- p reoperative bod y w eight experienced significantly few er
erate oral hyd ration. Solu tions containing only 5% d extrose card iop u lm onary and tissu e-healing com p lications than
are not effective volu m e expand ers (e.g., only 10% of the p atients assigned to the u su al flu id management (9). In
infu sed volu me rem ains w ithin the intravascular space) contrast, MacKay et al. d em onstrated no d ifference in the
(1). There are som e potentially ad verse effects of d extrose length of hosp ital stay com p aring p atients receiving
solu tions. Dextrose ad d s an ad d itional osm otic load to restricted and liberal flu id regim ens (10). These conflicting
crystalloid solu tions. In situ ations in w hich glu cose u tiliza- results m ay reflect variability in the patients stu d ied as w ell
tion is im p aired , such as critical illness, the infu sed glu cose as d ifferences in trial d esign and treatm ent regim ens. Based
m ay accu mu late and create an osm otic effect that can p ro- on available evid ence, it is not p ossible to m ake recom m en-
m ote d ehyd ration (2). Fu rther, d extrose infusions m ay the- d ations n w hat constitu tes op tim al intravenou s flu id u se in
oretically resu lt in increased CO 2 and lactate p rod u ction this context.
(4,5). This is of u ncertain clinical importance in m ost su rgi- A second ind ication for crystalloid u se is as replace-
cal p atients. ment therapy in ind ivid uals w ith either pre-existing or
ongoing flu id losses or electrolyte d istu rbances. The nature
Indications for Crystalloid Solution Use or sou rce of flu id loss m ay lead to p red ictable electrolyte
Crystalloid s are used in several situ ations, perhap s m ost abnorm alities and d ictate the com p osition of the intra-
com m only as a m aintenance fluid . Maintenance flu id s venou s flu id to be u sed . While a d etailed d iscu ssion of all
mu st rep lace the app roxim ately 75 m Eq of N a lost d aily the conceivable electrolyte abnorm alities occu rring in gen-
and p rovid e ap p roxim ately 40 to 50 m Eq/ d of K (6). eral su rgical p atients is beyond the scop e of this chap ter,
Becau se of the large bod y stores and lim ited d aily losses of tw o com m only encou ntered scenarios m erit m ention. The
Ca 2 and Mg 2 , m aintenance replacem ent of these ele- m ost com m on electrolyte abnorm ality observed in general
m ents is u nnecessary in p atients that requ ire a short cou rse su rgical p atients is hyp okalem ic, hyp ochlorem ic m etabolic
of intravenou s therapy (6). For a patient w ith intact renal alkalosis resu lting from loss of gastric secretions via naso-
and card iop u lmonary function, a com m on m aintenance gastric tu bes. This electrolyte abnorm ality is a chlorid e
flu id p rescrip tion is Dextrose 5%/ 0.45% N aCl w ith su p p le- resp onsive alkalosis; accord ingly, its correction requires
m ental KCl (20 m Eq/ L) or D5LR infused at 1 to 2 m L/ ad m inistration of a Cl sou rce in ad d ition to supp lem ental
kg/ hr. The p resence of acute or chronic organ d ysfu nction K (e.g., normal saline w ith su pplemental KCl). For patients
frequ ently requ ires m od ification of the volu m e or com p osi- w ho have su bstantial nasogastric losses ( 1 L/ d ), serial
tion of flu id infu sed . For m ost general su rgical p atients electrolytes shou ld be d eterm ined d aily and this abnorm al-
requ iring short cou rses of intravenou s therapy, su ch as ity shou ld be anticip ated and corrected accord ingly. A sec-
those aw aiting resolu tion of postop erative ileu s, it is not ond electrolyte d istu rbance frequ ently encou ntered in
necessary to d eterm ine seru m electrolyte concentrations on su rgical p ractice is m etabolic acid osis second ary to high
a frequ ent (e.g., d aily) basis. H CO 3 loss, su ch as occu rs in the p resence of p roxim al
H istorically, liberal approaches to flu id volu me infu sion sm all bow el enterocu taneou s fistu la. Lactated Ringer ’s
have been u tilized em p irically in the p eriop erative p eriod solu tion, becau se it contains a H CO 3 sou rce, is the ap pro-
to cou nteract the effects of fasting, third space flu id shifts, p riate rep lacem ent flu id in this setting.
and other factors that m ight result in intravascular volu m e A third ind ication for crystalloid u se is resuscitation.
d ep letion (7). Su ch an approach has been challenged Crystalloid s are approp riate as a first line treatment of
recently by stu d ies su ggesting a relationship betw een the shock, regard less of etiology, and have the ad vantages of
volum e of flu id infu sed in this context and clinically being inexp ensive, read ily available, and reaction free.
im p ortant ou tcomes. In a small p rospective trial, Lobo et al. Excessive crystalloid ad m inistration m ay resu lt in p erip h-
rand om ized p atients to receive either stand ard flu id ther- eral and p u lm onary ed em a, w hich m ay occu r before
ap y (d efined as volu m e exceed ing 3 L/ d and sod iu m load intravascu lar volu m e is com p letely restored . Ind icators of
of 154 m Eq/ d or greater) or flu id restriction (fluid volu m e ad equ ate resu scitation, su ch as central venou s pressu re,
not exceed ing 2 L/ d and sod iu m load not exceed ing p u lm onary cap illary w ed ge p ressu re, or end organ fu nc-
77 m Eq/ d ) follow ing elective colon surgery (8). Gastric tion, shou ld gu id e the volu m e of crystalloid ad m inistered ,
as w ell as the need for other m eans of hem od ynam ic volu m es of infu sion not to exceed 1,500 mL/ d , though infu-
sup port (e.g., p acked red blood cell transfu sion or cate- sions of larger volumes in a 24-hou r period appear w ell tol-
cholam ine vasop ressors) (11). As d iscu ssed below, d ebate erated (1). H yd roxyethyl starch should be ad m inistered
continu es regard ing the relative ad vantages and d isad van- w ith caution in ind ivid uals w ith significant coagulopathy
tages of crystalloid s for this ind ication. or bleed ing d iathesis (1). In a recent prospective trial con-
d ucted in patients w ith sepsis, resuscitation w ith hyd rox-
yethyl starch w as associated w ith higher rates of renal
■ Colloids failure and mortality compared w ith resuscitation using lac-
Colloids contain a m olecu le w ith a large m olecular w eight tated Ringer ’s solution (14).
that d oes not m igrate read ily across the cap illary m em - Dextrans are glu cose p olym ers that are available in tw o
brane as the p rincip al osm otically active substance (1). Col- p rep arations: 10%, Dextran 40, and 6%, Dextran 70, w ith
loid infu sions have the effect of prim arily expand ing the m olecu lar w eights of 40 kDal and 70 kDal resp ectively (1).
intravascu lar sp ace (2). In contrast w ith crystalloid s, w hich Sm all d extran p articles are rap id ly excreted renally, w hile
have a nu m ber of p otential u ses, the prim ary ind ication for d extran m olecu les larger than 55 kDal have half-lives of
colloid ad m inistration is acu te volum e expansion. several d ays. Becau se of its significantly longer half-life,
The p rototyp ical colloid solu tions are albumin p rep a- Dextran 70 is m ore com m only u sed for volu m e expansion.
rations. Albu m in is the p rotein fou nd m ost abu nd antly in A 6% d extran solu tion in an isotonic d ilu ent is rou ghly
p lasm a, accou nting for as m u ch as 85% of the colloid com p arable to a 6% hetastarch solu tion in cap acity for vol-
osm otic p ressu re p resent. H u m an seru m albu m in is com - u m e exp ansion. The p rincip le d isad vantage of d extran
m ercially available in an isotonic d ilu ent as both a 5% solu tions is coagu lop athy. Dextran p rod u ces a d ose related
solu tion (50 g/ L) and a 25% solu tion (250 g/ L). These red uction in platelet fu nction and fibrin clot tensile
p rod u cts are heat-treated and p ose no risk of viral trans- strength, as w ell as an increase in fibrinolytic activity (1).
m ission (1). Ad m inistration of 5% albu m in p rep arations It is recom m end ed that d extran infu sions be lim ited to
exp and s the intravascu lar sp ace by rou ghly 50% of the 20 m L/ kg/ d or 1.5 g/ kg/ d (1). Dextrans are not w id ely
volu m e infu sed . In contrast, ad m inistration of 25% albu - u sed in the U.S. as resu scitation flu id s bu t are frequ ently
m in p rep arations exp and s the intravascu lar volu m e by an u sed as anticoagu lants.
am ou nt equ aling fou r- to fivefold the volu m e infu sed , d u e The m ajor d raw back to colloid u se is cost. Colloid s
to a shift of interstitial flu id into the intravascu lar sp ace. require an expense several tim es greater than crystalloid s
Tw enty-five p ercent albu m in solu tions are ad m inistered in to achieve the sam e d egree of volu m e exp ansion. Further,
sm all volu m es (50 to 100 m L); becau se the accom p anying in ad d ition to the ad verse effects noted , colloid s are associ-
sod iu m load is sm all, these p rep arations are also know n as ated w ith a very sm all risk of hyp ersensitivity (an inci-
“salt p oor albu m in.” Tw enty-five p ercent albu m in solu - d ence of 0.085% of infu sions or less, d ep end ing on the
tions shou ld not be ad m inistered to p atients w ho are p rep aration) (13).
hyp ovolem ic. While the focu s of this chap ter is the u se of
colloid s for resu scitation, albu m in has a nu m ber of other ■ Is colloid administration beneficial for
p otential ind ications (e.g., card iop u lm onary byp ass,
resuscitation?
hem od ialysis, acu te nep hrosis, hyp erbiliru binem ia, acu te
liver failu re, ascites, etc.) (12). Debates regarding the potential advantages and disadvan-
A nu m ber of other colloid solutions are available for tages of crystalloid or colloid administration have largely
clinical use. Hydroxyethyl starch (Hetastarch) is a synthetic centered on the relative efficiencies of these two classes of
colloid that has an average molecular w eight of 69 kDal, agents in achieving volume expansion, and by extension, the
making it p hysically com p arable to albu m in (13). H yd rox- effects of these relative volum es on clinically significant end -
yethyl starch is available as a 6% solu tion in isotonic points, such as d evelopment of acute lung injury and mor-
saline, w hich has an oncotic effect equ ivalent to a 5% albu - tality. The volume of crystalloids required for resuscitation
m in solu tion. H yd roxyethyl starch is a slightly m ore can be as much as 12-fold greater than the volume of colloid
p otent volu m e exp and er than albu m in (achieving an effec- solution required to reach the same hemodynamic endpoint
tive volu m e exp ansion of 30% m ore than the volu m e (1). Given the unique biological profile of albumin, (e.g.,
infu sed ). H ow ever, becau se the oncotic effect d issip ates antioxid ant, free rad ical scavenger, and d rug transporter),
w ithin 24 hou rs, this volu m e exp ansion is relatively short- coupled with the observation that hypoalbuminemia is asso-
lived . H yd roxyethyl starch m olecu les are cleaved by am y- ciated with adverse outcome in a number of disease states,
lases p resent in blood , p arenchym al tissu e, and the there may be an additional rationale for the use of albumin
reticu lar end othelial system (13). This gives rise to m ild preparations as resuscitation fluid s (12,15). Despite over five
hyp eram ylasem ia bu t d oes not ind icate p ancreatitis. Sim i- d ecad es of experience w ith albumin use, and reports from
larly, hyd roxyethyl starch infu sion p rod u ces p rolongation d ozens of clinical trials (enrolling thousand s of patients)
of the activated p artial throm bop lastin tim e that d oes examining the effects of albumin ad ministration as w ell as
not ap p ear associated w ith clinically significant bleed ing. the use of other colloids, little or no consensus exists cur-
Recom m end ations for hyd roxyethyl starch u se are for rently on the relative merits of these agents.
Benefit Harm
Hypovolemia 1.46 [ 0.97-2.22 ]

Cochrane Group (16)
Burns 2.40 [ 1.11-5.19 ]
Hypoalbuminemia 1.69 [ 1.07-2.67 ]
Overall 1.11 [ 0.95-1.28 ]
Wilkes et al. (12) Surgery or Trauma 1.12 [ 0.85-1.46 ]
Burns 1.76 [ 0.97-3.17 ]
Hypoalbuminemia 1.59 [ 0.91-2.78 ]
Hydroxyethyl starch 1.16 [ 0.68-1.96 ]

Alderson et al. (20) Dextran 1.24 [ 0.94-1.65 ]
Hypertonic saline with Dextran 70 0.88 [ 0.74-1.05 ]
0 1 2 3 4 5 6
Mortality Relative Risk
FIGURE 17.1. Meta-analyses of clinical studies comparing crystalloid and colloid resuscitation. Plots of point
estimates of relative risk of mortality (triangle) with 95% confidence intervals (horizontal lines) for all patients and
selective subgroups from meta-analyses of trials comparing crystalloids and colloids as a resuscitative strategy.
Data from Cochrane Injuries Group Albumin Reviewers (16), Wilkes et al. (12), and Alderson et al. (20). Relative risk of
1 is consistent with no effect on mortality (vertical line), relative risk less than 1 is consistent with beneficial effect of
colloid use relative to crystalloid use, relative risk greater than 1 is consistent with a harmful effect of colloid use rel-
ative to crystalloid use. While many of the 95% confidence intervals include 1, the relative risk point estimates
exceed 1 for many trials consistent with an adverse effect on survival with colloid use. It is estimated that a trial
enrolling approximately 6,000 patients would be necessary to convincingly demonstrate an effect of colloids as a
resuscitation fluid (19).
The m ost recent inform ation regard ing the benefits or Wilkes et al. rep orted a m eta-analysis of 55 trials (enrolling
risks of colloid therapy in resu scitation is provid ed by sev- rou ghly 3,500 p atients) comp aring crystalloid to albu m in
eral system atic literatu re analyses. (Fig. 17.1) In 1998, the therap y, again d em onstrating no statistically significant
Cochrane Grou p pu blished a m eta-analysis of 30 con- d ifference in overall m ortality (RR [95%CI] 1.11
trolled trials, enrolling over 1,400 patients, in w hich albu - [0.95 1.28]) (12). H ow ever, in an accom p anying ed itorial,
m in (or p lasm a p rotein fraction) infusion w as com p ared to Cook et al. noted that in both, all p atients stu d ied , as w ell
either crystalloid infusion or no specific treatm ent (16). as the variou s su bgrou p s analyzed (inclu d ing patients fol-
While there w as no overall effect of these colloid s on low ing su rgery or trau m a, bu rns, or hyp oalbum inemia),
su rvival in the case of hyp ovolem ia (relative risk of the use of album in is consistent w ith a harm fu l effect on
m ortality w ith 95% confid ence intervals; (RR [95%CI]) su rvival (19). Sim ilar analyses have exam ined trials that
1.46 [0.97 2.22]), in tw o subgroup s, those of patients w ith com p ared crystalloid resu scitation to either d extran or
bu rns and w ith hypoalbu m inem ia, album in ad m inistra- hetastarch, w ith no d iscernible benefit from any colloid
tion w as associated w ith an increased m ortality risk (RR class (20,21).
[95%CI] 2.40 [1.11 5.19] and 1.69 [1.07 2.67], resp ec- Meta-analyses are exp loratory and hyp othesis-generat-
tively) (16). Follow ing publication of this report, albu m in ing, and shou ld not be consid ered a su bstitu te for app ro-
u se in the United Kingd om d eclined d ram atically (17). p riately d esigned and controlled clinical trials (22).
Subsequ ently, Choi et al. reported on a m eta-analysis of 17 N onetheless, these and other techniqu es of second ary d ata
stu d ies enrolling ap proxim ately 800 patients that com- analysis are u sefu l for su m m arizing large nu m bers of clini-
pared infu sion of isotonic crystalloid s to albu m in (and cal trials and reconciling the resu lts of conflicting rep orts.
other colloid s) (18). While there w as no d ifference in treat- The stu d ies cited raise interesting and p otentially im p or-
m ent grou p s w ith resp ect to the p rimary end p oints of m ortant questions w ith regard to the safety and efficacy of col-
tality, p u lm onary ed em a, or length of hosp ital stay, colloid loid p rep arations as resu scitation flu id s (12,16,18). Based
infu sion ap p eared to ad versely affect su rvival in the su b- on existing literatu re, if colloid p rep arations have a
grou p of p atients follow ing trau m a (18). In ad d ition, clinically im p ortant effect on su rvival, either positively or
negatively, that effect is sm all (e.g., less than a 10% d iffer- su ggest that the u se of colloid solu tions p rovid es benefit
ence in m ortality), and w ould requ ire a stud y enrolling over that of crystalloid s as a resu scitation strategy. H ow -
nearly 6,000 p atients to d em onstrate (19). In the absence of ever, given the heterogeneity of the stu d ies p u blished to
unequ ivocal clinical evid ence and given the costs of m ost d ate, w ith resp ect to both p op u lations of p atients enrolled
colloid p rep arations relative to crystalloid s, it is d ifficu lt to and qu ality, colloid resu scitation m ay be of benefit in
recom m end their rou tine use as resuscitation fluid s. These selected circu m stances and cannot be exclu d ed as other-
agents are licensed and ap proved for a variety of ind ica- w ise. Finally, as evid enced by recent in vitro investigations
tions; w hether they are beneficial in these settings is not of hyp ertonic saline su ggesting m od u latory effects on
convincingly d em onstrated . inflam m ation and m icrocircu lation (29–31), fu tu re u ses of
intravenou s flu id s m ay possess therap eutic valu e beyond
volu m e and electrolyte rep lenishm ent.
■ Hypertonic saline
H yp ertonic saline is a very efficient volu m e exp and er. For
each m illiliter of hyp ertonic saline infu sed , ap p roxim ately
■ REFERENCES
7 m L of free w ater is d raw n into the extracellu lar sp ace 1. Rainey TG, Read CA. Pharm acology of colloid s and crystalloid s. In:
Chernow B, ed . The pharmacological approach to the critically ill patient.
(1). The intravascu lar hyp ertonic benefit d issip ates w ithin Baltim ore: William s & Wilkins; 1994:272–290.
15 m inu tes as a resu lt of equ ilibration betw een the 2. Marino PL. Colloid and crystalloid resu scitation. In: Marino PL, ed . The
intravascu lar and interstitial com p artm ents. To achieve a ICU book. Baltim ore: William s & Wilkins; 1998:228–241.
3. Jonasson O. Surgical asp ects of d iabetes m ellitu s. In: Sabiston DC,
m ore su stained effect, hyp ertonic saline is typ ically co- Lyerly H K, ed s. Textbook of surgery. Philad elp hia: W.B. Sau nd ers Co.;
infu sed w ith a colloid (m ost clinical trials have u sed Dex- 1997:176–185.
tran 70). H yp ertonic saline infu sion m ay theoretically be 4. Degou te CS, Ray MJ, Manchon M, et al. Intraop erative glu cose infu sion
and blood lactate: end ocrine and m etabolic relationship s d u ring
of benefit in p atients follow ing head trau m a. By increas- abd om inal aortic su rgery. Anesthesiology 1989;71:355–361.
ing system ic blood p ressu re, hyp ertonic saline im p roves 5. Talp ers SS, Rom berger DJ, Bu nce SB, et al. N u tritionally associated
cerebral blood flow. Unlike other crystalloid s, hyp ertonic- increased carbon d ioxid e p rod u ction. Chest 1992;102(2):551–555.
6. O’ Flaherty D, Giesecke AH . Crystalloid flu id therap y. In: N im m o WS,
ity antagonizes the d evelop m ent of cerebral ed em a and Rom botham DJ, Sm ith G, ed s. Anaesthesia. Lond on: Blackw ell Scientific
intracranial hyp ertension, and m ay resu lt in im p rove- Publications; 1994:554–567.
m ent of cerebral p erfu sion p ressu re (23). There have been 7. Jacob M, Chap pell D, Rehm M. Clinical u p d ate: p eriop erative flu id
m anagem ent. Lancet 2007;369:1984–1986.
several p rosp ective, rand om ized evalu ations to d eter- 8. Lobo DN , Bostock KA, N eal KR, et al. Effect of salt and w ater balance
m ine the feasibility of hyp ertonic saline as a p rehosp ital on recovery of gastrointestinal fu nction after elective colonic resection:
resu scitation strategy. N one of these stu d ies show ed a a rand om ized controlled trial. Lancet 2002;359:1812–1818.
9. Brand stru p B, Tonnesen H , Beier-H ogersen R, et al. Effects of intra-
convincing benefit of hyp ertonic saline u se (24–26). Sim i- venou s flu id restriction on p ostop erative com p lications: com p arison of
lar find ings w ere rep orted in a second ary d ata analysis tw o p eriop erative flu id regim ens. Ann Surg 2003;238:641–648.
that involved 17 trials enrolling 869 p atients (23). (Fig. 10. MacKay G, Fearon K, McConnachie A, et al. Rand om ized clinical trial
of the effect of p ostop erative intravenous flu id restriction on recovery
17.1) Given that the trials analyzed w ere sm all, inclu d ed after elective colorectal su rgery. Br J Surg 2006;93:1469–1474.
heterogeneou s p atient p op u lations, and w ere of variable 11. Freem an BD, N atanson C. H yp otension, shock, and m u ltip le organ
qu ality, the p ossibility that hyp ertonic saline m ight be of failu re. In: Wachter RM, Gold m an L, H olland er H , ed s. Hospital medi-
cine. Baltim ore: Lip p incott William s & Wilkins; 2000:123–132.
benefit cou ld not be exclu d ed (23). A large m u lticenter 12. Wilkes MM, N avickis RJ. Patient su rvival after hu m an albu m in ad m in-
trial com p aring p rehosp ital resu scitation u sing hyp er- istration. Ann Intern Med 2001;135:149–164.
tonic saline w ith isotonic solu tion in severely inju red 13. Ratner LE, Sm ith GW. Intraop erative flu id m anagem ent. Surg Clin
North Am 1993;73(2):229–241.
p atients is ongoing (27). In the absence of resu lts from 14. Bru nkhorst FM, Engel C, Bloos F, et al. Intensive insu lin therap y and
d efinitive stu d ies, hyp ertonic saline cannot be recom - pentastarch resu scitation in severe sep sis. N Engl J Med 2008;358(2):
m end ed for rou tine u se. 125–139.
15. Gold w asser P, Feld m an J. Association of seru m albu m in and m ortality
risk. J Clin Epidemiol 1997;50:693–703.
■ CONCLUSION
16. Cochrane Inju ries Grou p Albu m in Review ers. H u m an albu m in ad m in-
istration in critically ill patients: system atic review of rand om ized con-
trolled trials. Br Med J 1998;317:235–240.
Desp ite a history d ating back over 150 years, intravenou s 17. Roberts I, Ed w ard s P, McLelland B. More on albu m in. Use of hu m an
fluid therapy continues to be an area of d ebate and investi- albu m in in UK fell substantially w hen system atic review w as p u b-
gation (28). This chapter has attem p ted an evid ence-based lished . Br Med J 1999;318:1214–1215.
18. Choi PTL, Yip G, Qu inonez LG, et al. Crystalloid s vs. colloid s in flu id
app roach to gu id e p rescription of representative com mer- resu scitation: a system atic review. Crit Care Med 1999;27(1):200–210.
cially available intravenou s fluid s. With the excep tions 19. Cook DJ, Guyatt G. Colloid u se for flu id resu scitation: evid ence and
noted , the p red om inantly u sed crystalloid solu tions (e.g., spin. Ann Intern Med 2001;135(3):205–208.
20. The Albu m in Review ers (Ald erson P, Bu nn F, Li Wan Po A, et al.).
lactated Ringer ’s solu tion or 0.9% N aCl) and their resp ec- H um an albu m in solution for resu scitation and volum e expansion in
tive d erivatives m ay be u sed interchangeably for m ainte- critically ill p atients. Cochrane Database Syst Rev 2004; (4): CD001208.
nance therap y and as resu scitation flu id s. Use of these DOI: 10.1002/ 14651858.CD001208.p u b2.
21. Perel P, Roberts IG. Colloid s versu s crystalloid s for flu id resu scitation
agents as rep lacem ent flu id s shou ld be ind ivid ualized to in critically ill p atients. Cochrane Database Syst Rev 2007; (4): CD000567.
the clinical situ ation. The bu lk of clinical evid ence d oes not DOI: 10.1002/ 14651858.CD000567.p u b3.
22. Freem an BD, Gerstenberger EP, Banks S, et al. Using second ary d ata in 27. Brasel KJ, Bulger E, Cook AJ, et al. H yp ertonic resu scitation: d esign
statistical analysis. In: Gallin JI, ed . Principles and practice of clinical and im p lem entation of a p re-hosp ital intervention trial. J Am Coll Surg
research. San Diego, CA: Acad em ic Press; 2002:251–257. 2008;206(2):220–232.
23. Bunn F, Roberts I, Tasker R, et al. H yp ertonic versu s isotonic crystal- 28. Cosnett JE. The origins of intravenou s flu id therap y. Lancet 1989;
loid for flu id resu scitation in critically ill p atients. Cochrane Database 333(8641):768–771.
Syst Rev 2004; (3): CD002045. DOI: 10.1002/ 14651858.CD002045. p u b2. 29. Gu shchin V, Alam H B, Rhee P, et al. cDN A p rofiling in leu kocytes
24. Mattox KL, Maningas PA, Moore EE, et al. Prehospital hypertonic exp osed to hypertonic resu scitation flu id s. J Am Coll Surg 2003;197(3):
saline/ d extran infu sion for post-trau m atic hyp otension. Ann Surg 1991; 426–432.
213(5):482–491. 30. Shield s CJ, O’Su llivan AW, Wang JH , et al. H yp ertonic saline enhances
25. Vassar MJ, Fischer RP, O’Brien PE, et al. A m u lticenter trial of resu scita- host response to bacterial challenge by augm enting receptor-ind epend -
tion of inju red patients w ith 7.5% sod iu m chlorid e. Arch Surg 1993;128: ent neu trop hil intracellu lar su p eroxid e form ation. Ann Surg 2003;
1003–1013. 238(2):249–257.
26. Wad e CE, Kram er GC, Grad y JJ, et al. Efficacy of hyp ertonic 7.5% saline 31. Pascu al JL, Khw aja KA, Chau d hu ry P, et al. H yp ertonic saline and the
and 6% d extran-70 in treating trau m a: a m eta-analysis of controlled m icrocircu lation. J Trauma 2003;54(5, Su p p l):S133–S140.
clinical trials. Surgery 1997;122:609–616.
CHAPTER
18
Acute Renal Failure

Robert E. Southard and Craig M. Coopersmith
■ DEFINITION AND EPIDEMIOLOGY RIFLE criteria are a significant im provem ent over past d ef-
initions of ARF. Since their initial d escrip tion, the RIFLE
Acu te renal failu re (ARF) d evelops in 2% to 7% of hosp ital- criteria have been valid ated in num erous stud ies and allow
ized p atients, an incid ence that has rem ained stable for the clinicians and researchers to u se a uniform classification
last 25 years. Su rgery is a com m on cau se of ARF and system to d efine their p atients.
accounts for 20% to 50% of all hospital-acquired cases,
m aking it the second m ost com m on cau se of hosp ital-
acqu ired ARF. ARF is associated w ith m arked ly w orse ou t-
■ RISK FACTORS
com es after su rgery, w ith patients requiring d ialysis in the Mu ltip le risk factors contribu te to the d evelop m ent of ARF
p ostop erative p eriod having m ortalities greater than 50% in the p ostop erative setting, of w hich the m ost im p ortant is
(1). Ad d itionally, p ostoperative ARF increases both the p re-existing renal d ysfu nction (Table 18.2). Diabetics have
length and cost of hospitalization (2). H ow ever, if p atients been rep orted to have a 7% incid ence of ARF follow ing
w ith ARF su rvive, they are likely to recover renal fu nction general su rgical p roced u res, w hich increases to 20% to 30%
p rior to d ischarge. This has been d em onstrated by a recent in d iabetic p atients w ith concom itant infection, p eripheral
m u lticenter stu d y show ing that only 14% of intensive care vascu lar d isease, and / or p erip heral neu rop athy (1). Dia-
u nit (ICU) p atients w ith ARF requ ired renal replacem ent betics also have a ten-fold greater risk of d eteriorating renal
therap y (RRT) at d ischarge (3). fu nction in the p resence of hyp ovolemia. Patients w ith pre-
Although ARF is a commonly encountered complication, existing renal insu fficiency and d iabetes m ellitu s are p artic-
there has historically been no w ell-accepted definition of it. u larly susceptible to toxic reactions to rad iocontrast d ye.
Various stud ies have used absolute or relative increases in The eld erly are also esp ecially su scep tible to ARF d u e to
serum creatinine or blood u rea nitrogen, d ecreases in crea- the aging kid ney’s loss of fu nctional reserve and inability
tinine clearance, and need for RRT as d efinitions of ARF. to w ithstand acu te insu lts, as w ell as the fact that old er
This variability in d efinition m ad e clinical stu d ies d ifficu lt p atients typ ically have m ore com orbid ities. Since glom eru-
to interp ret. For instance, it has previously been estim ated lar filtration rate (GFR) d ecreases w ith age, eld erly patients
that ARF d evelop s in 1% to 25% of ICU patients w ith m or- are m ore su scep tible to volu m e d ep letion second ary to the
tality rates ranging from 15% to 60% (4). Based on this, the inability of an aged kid ney to conserve salt and m axim ally
Acu te Dialysis Quality Initiative Grou p d eveloped the concentrate u rine. Sep sis also increases the risk of ARF in
RIFLE criteria as a consensu s d efinition and classification the p eriop erative setting. The incid ence of ARF is 16% in
schem e for acu te kid ney inju ry (AKI) (5). The RIFLE crite- sep tic su rgical intensive care u nit (SICU) p atients, com -
ria (risk, inju ry, failu re, loss, end -stage kid ney d isease) p ared to 1% to 7% in nonsep tic ICU p atients (6). ARF u su -
d efine AKI u sing five com ponents. The first three grad e the ally occu rs 3 d ays after the onset of sep sis and is associated
severity of AKI based on changes in either seru m creatinine w ith an increase in both morbid ity and m ortality.
criteria or u rine ou tpu t criteria (Table 18.1). The final tw o One u nd er-recognized risk factor for p eriop erative
com p onents of the RIFLE criteria involve clinical ou t- ARF is elevated intra-abd om inal p ressu re. Elevated intra-
com es. “Loss” is d efined as persistent AKI w ith com p lete abd om inal pressure can lead to abd ominal compartment
loss of renal fu nction for a p eriod greater than 4 w eeks, syndrome, w hich may cause ARF in addition to a number of
w hile end -stage kid ney d isease ind icates p erm anent renal other life-threatening abnormalities. Either acute or chronic
failu re. Althou gh they are likely to be u pd ated in the fu tu re factors can contribute to elevated intra-abd ominal pressure,
as biom arkers rep lace creatinine and u rine outpu t, the but the d evastating effects of abd ominal compartment
syndrome are more commonly seen w hen elevations in
intra-abd ominal pressure are acute (7). This can occur in a
Robert E. Southard: Washington University in St. Lou is w id e range of perioperative settings, and abdominal pres-
School of Med icine, Dep artm ent of Su rgery. sures should be measured w hen this is suspected . When a
Craig M. Coopersmith: Em ory University School of patient’s intra-abd ominal pressure is greater than 20 mm H g
Med icine, Departm ent of Su rgery. and new onset organ failure is d ocumented , abd ominal
174
Chapter 18 • Acute Renal Failure 175
Table 1 8 .1 Acu t e k id n ey in ju r y n et wor k st a gin g of a cu t e k id n ey in ju r y

Serum Creatinine (Cr) Criteria Urine Output Criteria
Risk Cr increase of 0.3 mg/dLor 0.5 mL/kg/h for 6 hours
150%–200% above baseline
Injury Cr increase 200%–300% above baseline 0.5 mL/kg/h for 12 hours
Failure Cr increase 300% or Cr 4.0 mg/dL 0.3 mL/kg/h for 24 hours or anuria
for 12 hours
decompression should be performed emergently as a life- treat reversible cau ses. A thorou gh history (inclu d ing
saving measure (7). recent m ed ications and exp osu re to rad iocontrast d ye),
Althou gh intraoperative inju ry to the renal collecting p h ysical exam in ation, an d p rop er d iagn ostic testing w ill
system cannot alw ays be avoid ed , its incid ence can be min- lead to the best clinical m anagem ent of p atients. Initial
im ized w ith carefu l p reoperative planning and intraopera- laboratory m easu rem ents shou ld inclu d e a basic m eta-
tive technique. Any patient w hose ureters are expected to be bolic p rofile, m easu rem ent of u rine electrolytes inclu d ing
d ifficult to id entify d uring laparotomy should have ureteral calcu lation of a fractional excretion of sod iu m (FEN a),
stents placed preoperatively. Intraoperative id entification of u rinalysis, and m easu rem ent of u rine osm olality. It shou ld
the ureters must also be perform ed d uring any case w here be noted that the resu lts of m ost of these tests are altered in
d issection and / or electrocautery could result in their inad - critical illness and m ay therefore be of less u tility in the
vertent d ivision. Finally, the type of operation p erformed ICU setting. In ad d ition, electrolyte con centrations in
correlates to risk of postoperative ARF. Proced ures that are u rine are affected by d iu retics and sp illage of glu cose
associated w ith higher rates of perioperative ARF are car- into the u rine; therefore, u rine electrolyte stu d ies are
d iac, thoracoabd ominal aortic, emergent abd ominal aortic, u nreliable in p atients w ho have recently received d iu ret-
liver transplant, and biliary proced ures (1). ics or th ose w ith h yp erglycem ia.
ARF m ay be classified by etiology or the am ount of
■ DIAGNOSIS AND CLASSIFICATION u rine p rod u ced p er d ay. For d iagnostic and therapeutic
p u rp oses, ARF is d ivid ed into p rerenal (12% to 60% of
An accu rate assessm ent of the etiology of ARF is cru cial cases), intrarenal (20% to 80% of cases), and p ostrenal (1%
to p revent fu rther w orsening of renal fu nction and to to 10% of cases) cau ses. Patients w ho have p rerenal ARF
typ ically have a FEN a of less than 1%, u rine osm olality
Table 1 8 .2 Risk fa ct or s for d evelop m en t of greater than 500 m Osm / kg, or u rine sod iu m concentration
p ost op era t ive a cu t e r en a l fa ilu r e less than 20 m Eq/ L. Prerenal ARF is m ost com m only
encou ntered in the setting of hyp ovolem ia. Ensuring ad e-
Pre-existing renal dysfunction qu ate volum e status w ith a fluid challenge and invasive
Age m onitoring, if necessary, is an im p ortant p art of the therapy
Left ventricular dysfunction (ejection fraction 35%, cardiac index of p ostop erative p atients w ith oligu ria or increasing seru m
1.7 L/min/m2) creatinine levels. When recognized early, p rerenal ARF is
read ily correctable w ith flu id resu scitation.
Hypertension
Patients w ith acu te tu bu lar necrosis (ATN ), the p re-
Peripheral vascular disease d om inant intrarenal cau se of ARF, typ ically have a FEN a of
Diabetes mellitus greater than 2%, u rine osm olality less than 400 m Osm / kg
Jaundice and u rine sod iu m concentration greater than 20 m Eq/ L. As
op p osed to p atients w ith p rerenal ARF (w ho m ay have no
Increased intra-abdominal pressure
find ings or have occasional hyaline casts on u rinalysis),
Chronic obstructive pulmonary disease p atients w ith ATN w ill generally exhibit renal tu bu lar
Cirrhosis epithelial cells and granu lar casts on m icroscopic analysis.
Sepsis ATN is p recip itated by ischem ia of the nephron, w hich
can be d u e to either d ecreased renal blood flow and oxygen
Use of nephrotoxic drugs or agents
d elivery or to increased oxygen u tilization cau sed by
Procedure type nep hrotoxins. Rap id id entification and reversal of renal
Cardiac
ischem ia is the m ost im portant m ethod of prevention of
Thoracoabdominal aortic
ATN . Intraop erative renal ischem ia m ay be u navoid able,
Emergency abdominal aortic
Liver transplant bu t shou ld be m inim ized as m u ch as p ossible. It m u st be
Surgery for biliary obstruction noted that p rolonged p rerenal ARF, if u ncorrected , ulti-
m ately lead s to intrarenal ATN .
Patients w ith p ostrenal ARF typ ically also have a It is essential to d eterm ine w hether the cau se of renal
FEN a of greater than 2% and u rine osm olality less than insu fficiency is prerenal hypoperfu sion or an intrinsic
400 m Osm / kg. Postrenal ARF occu rs w hen the u reters, event, becau se p rerenal ARF is com p letely reversible if
blad d er or u rethra are inju red or occlu d ed . It is im p ortant renal p erfu sion and glom eru lar filtration p ressu re are
to recognize ARF arisin g from obstru ction of the collect- restored rap id ly. Assessm ent of intravascu lar volu m e
ing system becau se this cond ition is often com p letely statu s is based u p on p hysical exam ination, u rine output,
reversible. laboratory valu es, and , p otentially, invasive m onitoring.
The m ost com m on cau se of u reteral d am age is iatro- Dep end ing u p on the severity of hyp ovolemia, the p atient
genic inju ry. Obstru ction or inju ry of the ureter shou ld be m ay p resent along a sp ectru m from su btle signs to card io-
su sp ected in any p atients w ith ARF after any p roced u re vascu lar collap se. The sim p lest method to exam ine volum e
d u ring w hich the u reter is at risk. Ureteral injury m ost statu s is m easu rem ent of u rine ou tp u t. A hyd rated patient
comm only occu rs d u ring p roced u res involving the d istal w ithou t a Foley catheter in p lace shou ld void at least once
colon and rectu m or gynecologic proced u res, bu t any p ro- every eight hou rs and m ake 0.5 m L/ kg/ h (280 m L per shift
ced u re involving retrop eritoneal or p elvic d issection can in a 70 kg p erson). If u rine ou tp u t ap p ears inad equ ate,
result in u reteral inju ry. A renal u ltrasound m ay be a u sefu l p lacem ent of a Foley catheter w ill aid in monitoring
d iagnostic stu d y w hen u reteral obstru ction is su sp ected as u rine volu m e. Tw o com m on clinical scenarios that resu lt
a cau se of ARF. Preoperative ureteral stent placem ent is in seem ingly ad equate urine ou tput d espite intravascular
comm only recom m end ed in situ ations w here inju ry to the hyp ovolem ia are hyp erglycem ia (an obligate osm otic
u reter is p ossible, although there is no prosp ective d ata to d iu resis can begin w ith glu cose levels greater than 180
su pp ort this p ractice. m g/ d L) and recent d iu retic ad m inistration. Patients w ith
Urethral obstruction is another cau se of postrenal ARF. elevated blood glu cose or those w ho receive d iuretics intra-
Gross hem atu ria, benign p rostatic hyp ertrophy, and u ri- op eratively therefore requ ire sp ecial attention to their
nary catheter obstru ction can lead to ou tflow obstru ction volu m e statu s since they can becom e m arked ly intravascu -
from the blad d er, resulting in ARF if not treated in a tim ely larly d ep leted and yet still appear to have ad equ ate u rine
fashion. The d evelop m ent of oliguria shou ld prom p t p lace- ou tp u t.
m ent of a Foley catheter. If there is alread y a catheter in Oligu ria in the p ostop erative p eriod u su ally reflects
place, the catheter shou ld be flushed to ensure it is d raining hyp ovolem ia. In ad d ition to m aintenance fluid s and
properly. rep lacem ent of blood loss, intraop erative insensible losses
Patients w ith ARF can also be subd ivid ed into those m ay be estim ated to be 1 to 3 m L/ kg/ h for a sm all incision,
w ith nonoliguric (urine output 400 mL/ d ), oligu ric (u rine 3 to 7 m L/ kg/ h for a m ed iu m incision and 9 to 11 m L/
outpu t 400 mL/ d ), and anuric renal failure (urine ou tp ut kg/ h for a large incision. While ad equ ate flu id resu scita-
50 mL/ d ). Patients w ith nonoligu ric renal failure have a tion shou ld be p erform ed intraop eratively by the anesthe-
better p rognosis, although there is no evid ence that “con- siologist, the su rgeon m u st verify each p atient’s fluid
verting” oligu ric ARF to nonoligu ric ARF w ith d iu retics balance in the im m ed iate p ostop erative p eriod and ad m in-
improves outcomes. ister ad d itional flu id if necessary. N early all p atients w ith
oligu ria in the p eriop erative p eriod are able to tolerate tw o
bolu ses of 500 m L of isotonic crystalloid solu tion or a single
■ PREVENTION
bolu s of 500 m L of a colloid . Sp ecial care shou ld be given to
Since ARF significantly w orsens prognosis, prevention of p atients w ith a severely d ecreased left ventricu lar ejection
ARF and / or m inim izing progression of the d isease is of fraction, those w ho are d ep end ent on high d ose d iu retic
utm ost im p ortance. H ow ever, d espite d ecad es of research p reop eratively, and those w hose op erations w ou ld not be
in how to p revent ARF, very few interventions have been expected to result in postop erative hyp ovolem ia.
rep rod u cibly su ccessfu l. For patients w ho d o not respond to initial flu id bolu ses,
the p hysician m u st d ecid e w hether to ad m inister ad d i-
tional flu id bolu ses or obtain ad d itional m onitoring. N o
■ Optimizing fluid status u niversal gu id elines can d ictate w hat constitu tes a “reason-
The single m ost im p ortant m easu re to p revent p eriop era- able” am ou nt of flu id ad m inistration before p u rsu ing ad d i-
tive ARF is m aintenance of ad equ ate intravascu lar volu m e. tional m onitoring. H ow ever, p atients w ith larger incisions
Depend ing on the clinical situation, this m ay range from and longer op erations m ay requ ire m ore flu id than average
aggressive flu id ad m inistration w ith isotonic crystalloid s su rgical p atients, and you nger p atients generally tolerate
or colloid s, to keep ing the patient on m aintenance flu id s to flu id overload better than old er ones. For p atients in w hom
balance their insensible losses. When the patient has an ad d itional inform ation is need ed to estim ate intravascu lar
ad equ ate card iac fu nction, eu volem ia ensu res sufficient volu m e, central venou s p ressu re (CVP) p rovid es a u sefu l
renal blood flow, red uces vasoconstrictive stim uli, and reflection of right heart filling p ressu res. This is relevant
im proves u rine flow. In contrast, prolonged renal hyp op er- becau se w hile hyp ovolem ia shou ld be avoid ed , the injud i-
fu sion and p rerenal ARF can lead to ATN and ultim ately ciou s u se of flu id s shou ld likew ise be avoid ed . For exam -
com plete renal failure. p le, a recent stu d y of flu id m anagem ent in p atients w ith
acu te resp iratory d istress synd rom e d em onstrated a strong serum creatinine are common, the need for RRT after con-
trend tow ard d ecreased risk of ARF requ iring d ialysis in trast ad ministration is low. The incid ence of CI-AKI is high-
patients treated w ith a conservative fluid m anagem ent est for noncoronary angiography and low est for CT scans
strategy (less flu id at a given CVP) than those w ith a liberal using intra venou s (IV) contrast (12).
fluid management strategy (8). The m ost effective therap y to p revent CI-AKI is ad m in-
In cases w here the CVP is a p oor estim ate of left heart istration of IV fluid arou nd the tim e of contrast ad m inistra-
filling volu m es (as occu rs w ith significant valvular d isease tion. Another com m only u sed therap y em p loys sod ium
or p u lm onary hypertension), a p ulmonary artery catheter bicarbonate. There have been arou nd 20 stu d ies pu blished
or esop hageal Doppler may be u sefu l. H ow ever, there is a on the u se of sod iu m bicarbonate to p revent CI-AKI (half of
pau city of convincing evid ence that these d evices p revent these have been only in abstract form ) w ith w id ely varying
renal failu re or im prove outcom es. In the unusu al event resu lts. Tw o recent m eta-analyses on the u se of sod iu m
that renal blood flow is lim ited by a p oor card iac ou tp u t, bicarbonate d em onstrate that the therap y has statistical
inotropic agents m ay be necessary as ad juvants to proper significance in p reventing CI-AKI bu t has no effect on need
fluid ad m inistration. for RRT or m ortality (13,14). Based on these resu lts as w ell
as the low qu ality and heterogeneity of m any of the stud -
ies, one m eta-analysis conclu d ed that “only a lim ited rec-
■ Blood pressure om m end ation can be m ad e in favou r” of u sing sod iu m
Another imp ortant factor in the m aintenance of renal per- bicarbonate for CI-AKI p rop hylaxis. If this strategy is u sed ,
fu sion is m ean arterial pressu re. While autoregu lation of the sod iu m bicarbonate solu tion is p rep ared by injecting
renal blood flow m ay be im p aired at m ean arterial p res- 154 m mol of sod iu m bicarbonate into 1 liter of 5% d extrose
sures less than 75 m m H g, tw o stud ies have show n no fu r- in w ater and ad m inistering it at a rate of 3 m L/ kg/ h for
ther im p rovem ent in u rine ou tp u t w ith m ean arterial 1 hou r p rior to contrast ad m inistration, and then at 1 m L/
pressu res greater than 65 m m H g (9,10). While this m eans kg/ h for 6 hou rs after the p roced u re.
that m ost p atients w ith p ossible renal hyp op erfu sion N -acetylcysteine (N AC) is another w id ely stud ied ther-
shou ld have their m ean arterial p ressu re kept above 65 m m apy to prevent CI-AKI. N AC is thought to act as a free rad i-
H g, in eld erly p atients and patients w ith pre-existing cal scavenger and ameliorate ischemia-reperfusion injury.
hyp ertension, au toregu lation of renal blood flow is fre- NAC is usually ad ministered as 600 mg dosed orally tw ice
qu ently im p aired , and these patients m ay benefit from d aily w ith at least one d ose prior to the proced ure and con-
higher arterial p ressures (11). tinued for at least 1 d ay afterw ard . Over 25 stud ies on the
utility of NAC have yielded conflicting results. The tw o
most recent meta-analyses (published in 2008 and 2009)
■ Avoidance of nephrotoxins d emonstrate a benefit of N AC in preventing CI-AKI (15,16);
The u se of nep hrotoxins shou ld be m inim ized or altogether how ever, no benefit w as seen in a 2007 meta-analysis (17).
avoid ed if p ossible. Once a patient d evelops ARF, a p rom p t Like sod ium bicarbonate, N AC has not been shown to pre-
review of the p atient’s recent m ed ications shou ld be u nd er- vent the need for RRT or d ecrease mortality. NAC is also
taken to d iscontinue agents if safe alternatives exist. The similar to sod ium bicarbonate in that both therapies are
nep hrotoxins m ost com m only encou ntered in the su rgical inexpensive and carry little risk. It is of note that preopera-
patient inclu d e rad iocontrast d ye (d iscussed below ), nons- tive use of N AC has also been stud ied in over 1,000 patients
teroid al anti-inflam m atory d ru gs (N SAIDs), cyclosp orine, to d etermine w hether it can prevent ARF in patients und er-
aminoglycosid es, and am photericin B. Once a p atient going major surgery w ho d o not receive rad iocontrast. N AC
d evelop s ARF, the renal clearance of m any d ru gs w ill also has no effect on either CI-AKI or mortality in this setting and
be d ecreased , occasionally resu lting in nephrotoxic levels is therefore not recommend ed for this usage (18). Multiple
of a d ru g in p lasm a. Vancom ycin is the m ost com m only other agents includ ing fenold opam, d opamine, furosemid e,
encountered d ru g in this category and should be avoid ed mannitol, and theophylline have been stud ied to d eterm ine
in evolving renal failure if possible; otherw ise trough levels w hether they prevent CI-AKI (15). None of these have been
shou ld be follow ed closely. proven to be beneficial. Additionally, furosemide has been
show n to increase serum creatinine after IV contrast admin-
istration so should not be used in this setting.
■ Contrast induced acute kidney injury
Contrast ind u ced acute kid ney injury (CI-AKI) accou nts for
10% of ARF in hospitalized patients. Although nephrop athy
■ Diuretics
ind u ced by rad iocontrast d ye is u ncom m on in p atients w ith The rationale for u sing d iu retics to prevent ARF is based on
norm al renal fu nction, its incid ence increases to 5% in the observation that nonoliguric renal failure has a better
patients w ith mild renal insufficiency and 50% in those w ith p rognosis than oligu ric renal failu re. H ow ever, m u ltiple
severe renal d ysfunction and d iabetes. CI-AKI is frequently rand om ized trials have failed to show im p rovem ent w ith
d efined as an increase in serum creatinine of at least 0.5 mg/ d iu retic u se. In a trial rand om izing 126 p atients u nd ergo-
d L or 25% above the baseline. While transient increases in ing card iac su rgery to fu rosem id e, d op amine, or p lacebo,
patients w ho received furosem id e had higher rates of ARF Table 1 8 .3 In d ica t ion s for r en a l r ep la cem en t
and higher seru m creatinine than those w ho received either t h era py
d opam ine or p lacebo (19). Sim ilarly, a large retrosp ective
stud y of 552 p atients d emonstrated that patients w ho Volume overload
received d iu retics early in the evolu tion of ARF w ere less Electrolyte abnormalities (e.g., hyperkalemia)
likely to recover renal function than those w ho d id not
Acidosis
receive d iu retics (20). Thu s, w hile d iu retics m ay p lay a role
in helping the physician m anage flu id statu s (to treat pu l- Symptomatic uremia (e.g., encephalopathy, pericarditis)
monary ed em a, for exam ple), they shou ld not be u sed as a Acute poisoning
method of preventing ARF.
collecting system . H ow ever, once a p atient has d eveloped

■ Dopaminergic agonists ATN , there are no therap ies p roven to hasten the return of
Low -dose (“renal dose,” 1 to 3 g/ kg/ min) dopamine has renal fu nction, and care is generally su p p ortive. Mainte-
been studied for over 30 years and is still widely used by nance of renal perfu sion is im p ortant as inju ry to the renal
many practitioners. Although numerous theoretical benefits tu bu les extend s in the first 24 hou rs after the onset of ATN
of low dose dopamine exist, it is an ineffective agent in pre- d u e to inflam m ation and vascu lar congestion. Avoid ance
venting ARF. While low-dose dopamine is frequently suc- of nep hrotoxins in this p eriod is im p erative.
cessful in improving urinary output, it does not alter Ultim ately, ARF either respond s to conservative therap y
mortality, the need for dialysis, or the onset of ARF. Both a or progresses to the point that patients require RRT. Ind ica-
prospective randomized trial on this agent in patients with tions for d ialysis are listed in Table 18.3. Although these
the systemic inflammatory response syndrome and oliguria ind ications are generally accepted , there is no absolute
(21) as well as a recent meta-analysis of 24 studies involving threshold for any of these ind ications that requires initiation
over 1,000 patients demonstrate this (22). Because low-dose of RRT; thus, the timing of initiation of RRT is clinician
dopamine may w orsen splanchnic oxygenation, impair GI d epend ent. H ow ever, a recent observational stud y in
function, impair endocrine and immunologic systems, and 54 ICUs d emonstrated that initiation of RRT “late” (d efined
blunt ventilatory drive w hile not preventing ARF, dialysis, or as 5 d ays after ad mission) w as associated w ith a longer
mortality, this strategy should not be used in clinical practice. d uration of RRT, hospital stay, and d ialysis d epend ence
Fenold opam is a d opam ine analogue that is specific (24). This is consistent w ith a stud y of 69 patients w ho
for the d op am ine-1 recep tors. Fenold op am theoretically d eveloped ARF after card iac surgery, in w hich patients ran-
increases renal blood flow w ithout the vasoconstrictive d omized to receive RRT for oliguria received d ialysis earlier
effect that m ay lim it the u sefu lness of d op am ine. Althou gh than those w ho received it based upon serum creatinine or
no large rand om ized trials have d em onstrated a m ortality potassiu m had significantly low er mortality (25)
benefit w ith fenold opam , a recent m eta-analysis of m ore There are several modalities of RRT, including intermit-
than 1,000 p atients in 13 trials conclu d es that fenold op am tent hemodialysis, sustained low-efficiency daily dialysis,
d ecreases the need for RRT and m ortality in patients and continuous venovenous hemodialysis. While hemod y-
und ergoing card iovascular surgery (23). Although its rou - namically unstable patients may not tolerate intermittent
tine u se cannot be recom m end ed for the p revention of ARF hemodialysis, there are no differences in clinical outcomes
at this tim e, a large clinical trial to d efinitively stud y the with intermittent hemodialysis or continuous venovenous
effects of fenold opam follow ing su rgery is w arranted . hemodialysis in the hemodynamically stable patient. Addi-
tionally, a recent prospective randomized trial of 1,124 ICU
patients demonstrated that as long as dialysis is ad equate,
■ Other pharmacologic therapies intensive dialysis does not improve outcome (mortality, renal
Multiple other therapies have been tried for the prevention recovery) when compared to less-intensive dialysis (26).
of postoperative ARF w ith limited evid ence of their benefit. Tem p orary d ialysis in p eriop erative p atients w ith ARF
Calcium channel blockers may provid e some benefit in renal is typ ically initiated throu gh a large bore, d ou ble lu m en
transplant patients but their use for other ind ications has not central venou s catheter. The p referred site is the right inter-
been proven to be beneficial. Other therapies w ith potential nal ju gu lar vein, w hich yield s consistent flow rates and is
benefit but limited clinical evidence for efficacy include pen- technically sim p le. The fem oral veins m ay also be used for
toxifylline, theophylline, anaritid e, and nesiritid e (synthetic access, bu t long term p resence of fem oral venous access
atrial- and brain-type natriuretic peptid es, respectively.) p red isp oses the p atient to infection. The left su bclavian
vein often gives accep table flow rates, bu t large bore
catheters at this site m ay lead to throm bosis and stenosis of
■ Treatment the vein, com p licating long term access in the upper
The treatm ent of ARF d epend s on the etiology. Prerenal extrem ity if p ermanent RRT is requ ired . This is one of the
ARF typ ically resp ond s to increased renal p erfusion, and few instances in w hich the internal ju gu lar vein is p referred
postrenal ARF is treated by relieving the obstru ction of the over the su bclavian vein for vascu lar access, second ary to
the increased risk of infection in catheters p laced in the toxicity of m yoglobin to renal tu bu les. There is no clear evi-
internal jugu lar vein. d ence in p atients to d eterm ine the efficacy of alkalinizing
Com plications of d ialysis catheters are similar to those the u rine.
seen w ith the p lacem ent of any central venou s catheter. A retrosp ective review of 2,083 trau m a p atients d em on-
Im m ed iate com p lications inclu d e pneum othorax, arterial strated no d ifference in m ortality or need for RRT in
cannulation, bleeding, and air embolism. A common delayed p atients treated w ith m annitol and bicarbonate; how ever, a
com plication is catheter-related blood stream infection. trend tow ard better ou tcom es w as noted in p atients w ith
Catheter-related blood stream infection is m anifested by the highest creatine kinase levels ( 30,000 IU/ L.) (27)
fever, leu kocytosis, and hypotension in severe cases, and
althou gh this com plication can occur at any tim e, the risk
of infection increases the longer the vascu lar access d evice
■ SUMMARY
is in p lace. If no other sou rce of infection is ap p arent, the ARF is a p otentially life-threatening com plication of su r-
catheter shou ld be rem oved , and tw o sets of blood cu ltu res gery that p ortend s a negative ou tcom e. Patients w ith pre-
shou ld be d raw n. The patient should also be started on existing renal insu fficiency are at the highest risk of ARF.
broad -sp ectru m antibiotics until cu lture resu lts are know n. Patients d isp laying evid ence of ARF, su ch as oligu ria or
The d ecision to rem ove or keep a d ialysis catheter in a sep - increasing seru m creatinine, shou ld be rap id ly evaluated .
tic p atient w ith another p ossible sou rce of infection m u st Untreated prerenal and postrenal ARF m ay lead to ATN
be m ad e on an ind ivid u al basis. Another frequent com p li- and p rolonged renal failu re. These cond itions m ust be
cation of d ialysis access is throm bosis of the vessel into id entified and treated as soon as p ossible. Op tim izing flu id
w hich the catheter has been placed . Throm bosis is fre- statu s and avoid ing nephrotoxins are the only clearly bene-
qu ently clinically silent but can have significant im p lica- ficial methods of preventing ATN . Once a patient develops
tions for long-term d ialysis access if a p atient’s renal failu re ATN , there are no proven therapeutic interventions to has-
d oes not resolve. ten its reversal. Specific situations such as rhabd omyolysis,
Patients w ith chronic renal failure should be d ialyzed contrast administration, and abdominal compartment syn-
throu gh their p reviou sly p laced arteriovenou s fistu la (or, d rome are potentially treatable or preventable causes of ARF
mu ch less com m only, their peritoneal d ialysis catheter). and should be id entified rapid ly. Once a patient d evelops
While su rgery at another site should not im pact continu a- ind ications, RRT should be started . Except in the hemod y-
tion of d ialysis per se, perioperative hypotension increases namically unstable patient, there is no evid ence supporting
the risk of throm bosis of a p reviou sly p atent fistu la and preference of one mod e of RRT over another.
shou ld be avoid ed if p ossible.
One cau se of renal failu re that occu rs d isp rop ortion-
ately in the trau m a su rgery population is rhabd om yolysis. ■ REFERENCES
Rhabd om yolysis results from the d estru ction of skeletal 1. Carm ichael P, Carm ichael AR. Acu te renal failu re in the su rgical set-
mu scle, m ost com m only from crush inju ries. Other situ a- ting. ANZ J Surg 2003;73(3):144–153.
2. Dasta JF, Kane-Gill SL, Du rtschi AJ, et al. Costs and ou tcom es of acu te
tions in w hich su rgical p atients d evelop rhabd om yolysis kid ney inju ry (AKI) follow ing card iac su rgery. Nephrol Dial Transplant
inclu d e com p artm ent synd rom e, ischem ia-reperfu sion of 2008;23(6):1970–1974.
skeletal m u scle, and m u scle d estruction from p ositioning 3. Uchin o S, Kellu m JA, Bellom o R, et al. Acu te renal failu re in critically
ill p atients: a m u ltination al, m u lticenter stu d y. JAMA 2005;294(7):
d u ring long su rgical proced ures or in the ICU. Rhabd om y- 813–818.
olysis is associated w ith m yoglobinu ria. The excretion of 4. Kellum JA, Bellom o R, Ronco C. Definition and classification of acu te
myoglobin by the kid neys m ay lead to tu bu lar obstru ction kid ney inju ry. Nephron Clin Pract 2008;109(4):c182–c187.
5. Bellom o R, Ronco C, Kellu m JA, et al. Acu te renal failu re – d efinition,
and d irect inju ry to the nephron by m yoglobin. ou tcom e m easures, anim al m od els, flu id therap y and inform ation tech-
The treatm ent of ARF d ue to rhabd om yolysis, as w ith nology need s: the Second International Consensu s Conference of the
that for other form s of ARF, is su pportive, w ith sp ecial Acu te Dialysis Quality Initiative (ADQI) Grou p . Crit Care 2004;8(4):
R204–R212.
em phasis placed on m aintenance of intravascular volu m e. 6. H oste EA, Lam eire N H , Vanhold er RC, et al. Acu te renal failu re in
Because renal d am age resu lts from the m echanical obstru c- patients w ith sepsis in a su rgical ICU: p red ictive factors, incid ence,
tion of tu bu les by m yoglobin, there are theoretical ad vancom orbid ity, and ou tcom e. J Am Soc Nephrol 2003;14(4):1022–1030.
7. Cheatham ML. Abd om inal com p artm ent synd rom e. Curr Opin Crit
tages to enforcing d iu resis (w ith ad equ ate intravascu lar Care 2009;15(2):154–162.
volu m e). Mannitol, an osm otic d iu retic that d oes not enter 8. Wied em ann H P, Wheeler AP, Bernard GR, et al. Com p arison of tw o
cells and is freely filtered and not reabsorbed by the fluid -m anagem ent strategies in acu te lu ng inju ry. N Engl J Med 2006;
354(24):2564–2575.
tu bu les, not only flu shes necrotic tubular d ebris from 9. Bou rgoin A, Leone M, Delm as A, et al. Increasing m ean arterial p res-
nep hrons bu t also has free rad ical scavenging properties. sure in patients w ith septic shock: effects on oxygen variables and renal
The evid ence su p p orting m annitol is based u p on exp eri- fu nction. Crit Care Med 2005;33(4):780–786.
10. LeDou x D, Astiz ME, Carp ati CM, et al. Effects of p erfu sion p ressu re on
mental anim al stu d ies and retrospective clinical stud ies, tissu e p erfu sion in sep tic shock. Crit Care Med 2000;28(8):2729–2732.
and there is no clear evid ence d em onstrating its efficacy in 11. Inscho EW. Lew is K. Dahl m em orial lectu re. Mysteries of renal
preventing and / or treating ARF in rhabd om yolysis. Main- au toregu lation. Hypertension 2009;53(2):299–306.
12. Weisbord SD, Mor MK, Resnick AL, et al. Prevention, incid ence, and
taining an alkaline (p H 6.5) urine has also been ad vo- outcom es of contrast-ind u ced acu te kid ney inju ry. Arch Intern Med
cated in the treatm ent of rhabd om yolysis to d ecrease the 2008;168(12):1325–1332.
13. H oste EA, De Waele JJ, Gevaert SA, et al. Sod iu m bicarbonate for pre- 21. Bellom o R, Chap m an M, Finfer S, et al. Low -d ose d op am ine in p atients
vention of contrast-ind u ced acu te kid ney inju ry: a system atic review w ith early renal d ysfu nction: a placebo-controlled rand om ised trial.
and m eta-analysis. Nephrol Dial Transplant 2009;25(3):747–758. Australian and N ew Zealand Intensive Care Society (AN ZICS) Clinical
14. N avaneethan SD, Singh S, Ap p asam y S, et al. Sod iu m bicarbonate ther- Trials Grou p . Lancet 2000;356(9248):2139–2143.
ap y for prevention of contrast-ind u ced nephrop athy: a system atic 22. Kellum JA, Decker M. Use of d op am ine in acu te renal failu re: a m eta-
review and m eta-analysis. Am J Kidney Dis 2009;53(4):617–627. analysis. Crit Care Med 2001;29(8):1526–1531.
15. Kelly AM, Dw am ena B, Cronin P, et al. Meta-analysis: effectiveness of 23. Land oni G, Biond i-Zoccai GG, Marino G, et al. Fenold op am red u ces
d rugs for p reventing contrast-ind u ced nep hrop athy. Ann Intern Med the need for renal rep lacem ent therap y and in-hosp ital d eath in card io-
2008;148(4):284–294. vascu lar su rgery: a m eta-analysis. J Cardiothorac Vasc Anesth 2008;
16. Trivedi H, Daram S, Szabo A, et al. High-dose N-acetylcysteine for the pre- 22(1):27–33.
vention of contrast-induced nephropathy. Am J Med 2009;122(9):874–815. 24. Bagshaw SM, Uchino S, Bellom o R, et al. Tim ing of renal rep lacem ent
17. Gonzales DA, N orsw orthy KJ, Kern SJ, et al. A m eta-analysis of therap y and clinical ou tcom es in critically ill p atients w ith severe acu te
N -acetylcysteine in contrast-ind u ced nephrotoxicity: unsu pervised kid ney inju ry. J Crit Care 2009;24(1):129–140.
clu stering to resolve heterogeneity. BMC Med 2007;5:32. 25. Dem irkilic U, Kuralay E, Yenicesu M, et al. Tim ing of rep lacem ent ther-
18. H o KM, Morgan DJ. Meta-analysis of N -acetylcysteine to p revent acu te apy for acu te renal failu re after card iac su rgery. J Card Surg 2004;
renal failu re after m ajor su rgery. Am J Kidney Dis 2009;53(1):33–40. 19(1):17–20.
19. Lassnigg A, Donner E, Gru bhofer G, et al. Lack of renop rotective effects 26. Palevsky PM, Zhang JH , O’Connor TZ, et al. Intensity of renal su p p ort
of d op am ine and fu rosem id e d u ring card iac su rgery. J Am Soc Nephrol in critically ill patients w ith acu te kid ney inju ry. N Engl J Med 2008;
2000;11(1):97–104. 359(1):7–20.
20. Mehta RL, Pascu al MT, Soroko S, et al. Diu retics, m ortality, and nonre- 27. Brow n CV, Rhee P, Chan L, et al. Preventing renal failu re in p atients
covery of renal function in acu te renal failure. JAMA 2002;288(20): w ith rhabd om yolysis: d o bicarbonate and m annitol m ake a d ifference?
2547–2553. J Trauma 2004;56(6):1191–1196.
CHAPTER
19
Pulmonary Complications
Mark R. Hemmila
■ INTRODUCTION exam ples of clinically significant pu lm onary com p lications

inclu d e atelectasis, p neu m onia, resp iratory failure w ith
The fire of life is maintained by the oxidation of metabolic p rolonged m echanical ventilation, exacerbation of u nd er-
substrates and the production of carbon dioxide. This creates lying chronic lu ng d isease, and bronchosp asm (4). Patient-
the kinetic energy that sustains all bodily functions. As a vital related risk factors that increase the risk of p ostop erative
organ, the lungs serve a dual role in allowing the absorption p u lm onary comp lications are old er age, m ale gend er,
of oxygen gas into the body and the excretion of carbon diox- sm oking, congestive heart failu re, m etabolic abnorm alities,
ide to the atmosphere. For surgical patients undergoing elec- and chronic obstru ctive p u lm onary d isease (COPD) (4,5).
tive or emergent operation, safe airway management and Proced u re related factors w hich increase risk are higher
maintenance of optimal pulmonary function are paramount Am erican Society of Anesthesiologists (ASA) classification,
to successful perioperative care. Pulmonary complications em ergency op eration, and m ore com p lex op eration (w ork
can occur on multiple levels and at varying rates of clinical relative valu e u nits) (5). Certain typ es of su rgery, su ch as
urgency. The successful clinician lives by the rule that thoracic and u p p er abd om inal p roced u res, are associated
“chance favors the prepared mind” and is ever vigilant for w ith a red u ction in fu nctional resid u al cap acity (FRC) (6).
compromise in a patient’s pulmonary function. Diap hragm atic d ysfu nction, p ostop erative p ain, and
Pulm onary complications span a w id e range of d ifferent sp linting are factors contribu ting to this loss in FRC. Loss of
etiologies bu t have a sim ilar resu lt in that they affect either FRC p laces the p atient at risk for atelectasis, pneum onia,
oxygenation or ventilation of the patient. The follow ing is a transp u lmonary shu nting, and imp aired gas exchange d ue
d iscussion of risk for pulmonary complications, d iagnosis, to ventilation/ p erfu sion m ism atch.
and management of life-threatening pu lmonary problems. Sm oking is a know n and rep eated ly d em onstrated risk
The pathogenesis, clinical presentation, prevention, and factor for p ostop erative p u lm onary com p lications. Sm ok-
treatment of severe pulmonary insufficiency w ill be cov- ing increases the relative risk of pu lm onary com plications
ered . Basic m anagem ent of m echanical ventilation in the am ong all p atients w ho sm oke as com p ared to nonsm okers
surgical patient w ith acute lung injury (ALI) w ill also be by an od d s ratio (OR) of 1.1 to 4.3 (5–9). This increased risk
d escribed , along w ith novel strategies to manage patients am ong sm okers extend s to those w ithou t chronic lu ng d is-
w ith severe acute respiratory d istress synd rome (ARDS). ease (7). In a p rosp ective stu d y of 200 p atients w ho und er-
w ent coronary artery byp ass su rgery, there w as a low er
■ PREOPERATIVE PULMONARY FUNCTION risk of p u lm onary com p lications in p atients w ho stop p ed
sm oking at least 8 w eeks p rior to su rgery than in current
■ Risk factors for pulmonary complications sm okers (15% vs. 33%) (10). Ironically, p atients w ho
Preop erative assessm ent of respiratory statu s and id entifi- ceased sm oking less than 8 w eeks before su rgery had an
cation of high-risk patients is of critical im p ortance in pre- increased risk of pu lm onary com p lications com pared to
venting p u lm onary com p lications in su rgery p atients. cu rrent sm okers (57% vs. 33%). Patients w ho stopped
Several p otential factors increase the risk of d evelop ing sm oking for more than 6 m onths had rates sim ilar to those
pu lm onary com p lications d uring or follow ing su rgery, as w ho never sm oked (11% vs. 12%).
outlined in Table 19.1. A respiratory com plication is General health statu s is an excellent d eterm inant of
d efined as any pulm onary abnorm ality that prod u ces id en- overall fitness for su rgical intervention and is an im p ortant
tifiable d isease or d ysfu nction that is clinically significant p red ictor of p u lm onary risk. The Gold m an card iac risk
and im p airs a p atient’s clinical cou rse (1–4). Im p ortant ind ex can pred ict pu lm onary as w ell as card iac com plica-
tions (11–13). The com m only u sed ASA classification,
w hich evalu ates overall risk of p eriop erative m ortality, has
Mark R. Hemmila: Traum a Burn Center, University of been show n to be an effective p red ictor of p ostoperative
Michigan Med ical School, University of Michigan H ealth resp iratory com p lications (5,14,15). An ASA class of 3 or
System , Ann Arbor, MI 48109. greater p laces the p atient at a 2.9-fold to 4.9-fold increased
181
Table 1 9 .1 Risk fa ct or s for d evelop in g Table 1 9 .2 Post op era t ive r esp ira t or y fa ilu r e
p ost op era t ive p u lm on a r y r isk in d ex
com p lica t ion s
Preoperative Predictor Point Value
Definite risk factors Type of surgery
Age 40 years Abdominal aortic aneurysm 27
Male gender Thoracic 21
Chronic obstructive lung disease Neurosurgery, upper abdominal, or peripheral vascular 14
Congestive heart failure Neck 11
Current smoking history
Cessation of smoking less than 8 weeks prior to surgery Emergency surgery 11
Poor general health status, defined as ASA class 2 Albumin ( 3 g/dL) 9
Serum albumin 3.5 gm/dL Blood urea nitrogen ( 30 mg/dL) 8
Serum creatinine 1.5 mg/dL
Emergency surgery Partially or fully dependent functional status 7
Type of operation (upper abdominal, thoracic, aortic, mouth/palate) History of chronic obstructive pulmonary disease 6
Complexity of operation
Age (years)
Surgery lasting greater than three hours
70 6
Use of pancuronium as a neuromuscular blocker
60–69 4
Probable risk factors
General anesthesia Predicted Probability of
Obstructive sleep apnea Class Point Total Pulmonary Failure
PaCO2 45 mm Hg 1 10 0.5%
Abnormal chest x-ray
2 11–19 2.2%
Current upper respiratory tract infection
3 20–27 5.0%
Modified from Smetana GW. Evaluation of preoperative pulmonary risk. UpToDate 4 28–40 11.6%
17.1. Available online at: http://www.utdol.com. Accessed May 20, 2009, with
permission. 5 40 30.5%
Adapted from Arozullah AM, Daley J, Henderson WG, et al. Multifactorial risk
index for predicting postoperative respiratory failure in men after major noncardiac
risk for p u lm onary com plications from general or vascu lar surgery. Ann Surg 2000;232:250, with permission.
surgery (5). Poor exercise tolerance is a strong id entifier of
patients at risk for p ulmonary com plications. For p atients
over 65, the inability to com plete 2 m inu tes of stationary cation continu e to be am ong the m ost im p ortant d eterm i-
bicycle exercise, su fficient to raise the heart rate to greater nants of respiratory failu re risk.
than 99 beats/ m inu te, w as the strongest pred ictor of p u l- Chronic lu n g d isease is the m ost im p ortan t p atient-
monary com plications in a m u ltivariate analysis of p atients related risk factor for p ostop erative p u lm on ary com p li-
und ergoing abd om inal or noncard iac thoracic surgery (13). cation s. Un ad ju sted relative risks of p ostop erative
The N ational Su rgical Qu ality Im p rovem ent Program com p lication s for p atien ts w ith COPD ran ge from 2.7 to
(N SQIP) is a m u lti-institu tional stu d y that has p rosp ec- 6.0 (4,17). Patients w ith severe COPD are up to six times
tively collected d ata on su rgical ou tcom es and com or- more likely to have a postoperative pulmonary com plica-
bid ities. The program relates this d ata to observed versu s tion than patients w ithout COPD (17). In a case control
expected m orbid ity and m ortality ratios u sing risk stud y of 164 patients und ergoing abd ominal surgery,
ad justed ind ices. A m ultifactorial risk ind ex m od el for p re- patients w ith abnormal find ings on lung examination
d icting p ostoperative respiratory failu re in men after m ajor consistent w ith COPD had an OR of 5.8 for pulm onary com-
noncard iac su rgery w as created from this stu d y (Table 19.2) plications (12). Med ical treatment of patients w ith sympto-
(16). A m ore robu st m od el now exists w hich applies to m en matic COPD should be optimized prior to elective general
and w om an u nd ergoing general or vascular su rgery and surgery. The use of bronchod ilators, physical therapy,
utilizes 28 p red ictive variables (5). Risk factor scores are antibiotics, smoking cessation, and in selected cases sys-
assigned for the 28 covariates and su m m ation of the ind i- temic corticosteroid s can red uce the risk of postoperative
vid u al covariate scores resu lts in the final risk factor complications in patients w ith COPD (4). Patients w ith
score. Patients w ith a risk factor score 8 (Low ) have a COPD have an increased risk for p ulmonary complications,
p red icted risk of resp iratory failu re of 0.2 %, those w ith a bu t there is no exact level of im paired p ulmonary fu nction
score betw een 8 and 12 (Med iu m ) have a risk of 1.0%, and below w hich all surgery is contraind icated . In a stud y of
p atients w ith a score 12 (H igh) have a 6.5% risk of resp i- 12 very high-risk su rgical p atients w ho all had an FEV1 of
ratory failu re. Op eration typ e id entified w ith cu rrent p ro- 1 L, only three of 15 surgeries w ere associated w ith post-
ced ural term inology (CPT) cod ing, operative com p lexity, operative complications, and there w ere no d eaths in these
need for em ergent su rgery, and preoperative ASA classifi- patients (18).
Chapter 19 • Pulmonary Complications 183
Age and obesity are tw o com m on risk factors that have m ance of a m axim al resp iratory inhalation and exhalation
been assu med to be associated w ith increased risk for p ul- m aneu ver in the clinic can be revealing. The ability to
monary complications. H ow ever, w hen d ata are analyzed clim b tw o flights of stairs at a constant p ace w ithou t d ys-
to accou nt for coexisting m ed ical cond itions, both of these p nea is a reasonable screening tool for d etecting p atients
risk factors are not alw ays ind epend ently pred ictive of w ith resp iratory, card iac, or joint d isease. Som e p atients
increased p ulmonary risk. The risk of surgical mortality is m ight be too obese, w eak, sed entary, or d ebilitated to
fairly similar for all age groups w hen stratified by ASA class com p lete this test. Inability to su cceed at this test shou ld
(19). A mu ltivariate analysis for postoperative respiratory p rom p t fu rther investigation into overall fitness for elec-
failure from the Patient Safety in Surgery Stud y id entified tive op eration, and corrective m easu res m ight need to be
age 40 years as a risk factor (5). Patients aged 40 to 65 had institu ted .
an OR of 1.7, and patients aged 65 had an OR of 2.1 for Mu ch confu sion and d ebate exists over the benefit of
pu lmonary com plications w hen compared w ith p atients p reop erative p u lm on ary fu nction testin g (PFT). Often
40 years of age. these tests confirm w hat is alread y clinically evid ent based
A review of ten p u blished series of bariatric su rgery on history and p hysical exam ination w ithou t ad d ing su b-
patients show ed a 4% incid ence of p neum onia and p ostop - stantially to the clinical estim ate of p u lm onary risk. A su b-
erative atelectasis, w hich is sim ilar to the general p op u la- set of p atients w ith reversible p u lm onary d isease on
tion (20). Prosp ective stu d ies show that a bod y m ass ind ex sp irom etry m ight benefit from aggressive correction w ith
25 kg/ m 2 is an ind ep end ent risk factor for p ostop erative bronchod ilators and anti-inflam m atory m ed ications. A
pu lm onary comp lications (9,21). Published d iscrep ancies 2006 Am erican College of Ph ysicians (ACP) consen su s
exist becau se the literature d oes not alw ays d istingu ish statem ent on p reop erative strategies to red u ce p eriop era-
betw een obesity and com orbid cond itions associated w ith tive p u lm onary com p lications for p atien ts u n d ergoing
obesity that can contribu te to increased pu lm onary risk. A noncard ioth oracic su rgery offered the recom m end ation
large review of six stu d ies w ith 4,526 patients show ed that that p reop erative PFTs or chest rad iograp hy m ay be
the risk for p u lm onary com p lications w as id entical for ap p rop riate in p atien ts w ith a p reviou s d iagn osis of
obese and nonobese p atients u nd ergoing abd om inal or COPD or asthm a (24). H ow ever, p reop erative sp irom etry
thoracic surgery (4). Com pared w ith norm al w eight an d ch est rad iograp h y shou ld n ot be u sed rou tinely for
patients, the m orbid ly obese patients (bod y m ass ind ex p red icting risk for p ostop erative p u lm onary com p lica-
35 kg/ m 2) have a higher risk of p ostop erative p u lm onary tions. The follow ing is an objective ap p roach to sp irom e-
em bolism w hich can resu lt in m ortality (22,23). H ow ever, try recom m end ed by Sm etana (6) and based on recent
in p atients u nd ergoing colectom y for cancer, the risk of literatu re:
pneu m onia w as not increased in the m orbid ly obese w hen
■ Obtain PFTs for patients w ith COPD or asthm a if clinical
ad ju stm ents w ere m ad e for other com orbid ities u sing
evaluation cannot d etermine w hether the patient is at his
N SQIP d ata (23). In sum m ary, the increase in risk for p u l-
or her best baseline and that bronchoconstriction is op ti-
m onary comp lications from age or obesity is sm all and is
mally red uced . Testing might id entify patients w ho w ill
probably more d irectly related to preexisting com orbid ities
benefit from m ore aggressive periop erative med ical man-
associated w ith these tw o cond itions.
agement and cond itioning.
■ Obtain PFTs for patients w ith d yspnea or exercise intol-
■ Preoperative assessment erance that is u nexp lained after clinical evalu ation.
■ PFTs should not be ord ered rou tinely prior to abd om inal
Patient history and p hysical exam ination are the classic
surgery or other high risk surgeries.
starting p oints for evalu ating p reop erative p u lm onary
■ PFTs shou ld not be u sed as the prim ary factor to d eny
risk. Id entification of find ings in the p atient history, su ch
surgery.
as exercise intolerance, d ysp nea on exertion, w heezing,
cigarette sm oking, cou gh, and sp u tu m p rod u ction, m ight A p reop erative arterial blood gas analysis id entifies
ind icate a need for m ore d etailed evalu ation of p u lm onary p atients w ith hyp ercap nia. N o d ata su ggest that carbon
fu nction. Physical exam ination shou ld focu s on d etecting d ioxid e retention increases p u lm onary risk beyond that
hyp oventilation in w eak or d ebilitated p atients and hyp er- alread y established on the basis of clinical risk factors
inflation in p atients w ith chronic p u lm onary d isease. recognized on history and p hysical exam ination. Patients
Wheezing, rales, or rhonchi on au scu ltation shou ld trigger w ith a Pa CO 2 of 45 m m H g u su ally have severe COPD,
fu rther exam ination. Physical evid ence of card iac insu ffi- w hich is an alread y id en tified risk factor associated w ith
ciency, obesity, cyanosis, tobacco u se, and p oor oral a p oten tial sixfold in crease in risk for p u lm onary com p li-
hygiene shou ld be consid ered a relative ind ication for p u l- cations. Preop erative arterial blood gas valu es serve p ri-
m onary fu nction assessm ent. m arily as a baselin e for p ostop erative com p arison and
A chest x-ray is p art of the com p lete evalu ation of any for d ecisions abou t p ostop erative ventilation rather than
p atient w ith abnorm alities d iscovered on history or p hys- as a screening test for ad equ acy of p u lm onary fu nction
ical exam ination. Chest x-ray shou ld also be rou tine for (25). Th e ACP recom m en d s p reop erative arterial blood
any p atient sched u led to u nd ergo thoracotom y. Perfor- gas analysis in th e follow ing p atien ts (26):
■ Patients sched uled to u nd ergo coronary artery bypass Table 1 9 .3 Sign s a n d sym p t om s of la r yn gea l
surgery or u pper abd om inal su rgery w ith a history of n er ve in ju r y
tobacco use or d yspnea.
■ All patients und ergoing form al lu ng resection. Voice Glottic Closure Airway
Recurrent
As w ith PFTs, p reoperative arterial blood gas analysis
Unilateral Weak Weak Good
alone cannot be the basis to id entify high risk patients or to Bilateral Normal Adequate Poor
d eny su rgery.
External branch, superior recurrent
Unilateral Lowered Weakened Good
■ ACUTE PULMONARY COMPROMISE Bilateral Lowered Loss of reflex Good
Combined injury
In the aw ake, alert, and conversive patient, patency and Unilateral Weak Poor Good
p rotection of the airw ay is a given. Du ring m ajor op era- Bilateral Weak Weak Adequate
tions the airw ay is u su ally orotracheally intu bated w ith a
cu ffed tu be that p rovid es a secu re cond u it for flow of resp i- Adapted from Newsome HH Jr. Complications of thyroid surgery. In: Greenfield LG,
ratory gases. Many surgical patients are at risk for acu te ed. Complications in surgery and trauma, 2nd ed. Philadelphia: J.B. Lippincott
Company; 1990:654, with permission.
p ulmonary com prom ise d u ring the im med iate periopera-
tive p eriod . A su rgical patient can experience acu te com -
p rom ise in his or her resp iratory status for several reasons. d angerou s d egree of airw ay com p rom ise has d eveloped , as
evid enced by nasal flaring, su bcostal retraction, and u se of
accessory m u scles, the p atient shou ld be p rep ared for
■ Loss of airway im m ed iate tracheostom y. Oral tracheal intu bation m ight
Patients w ho have u nd ergone neck operations su ch as be extrem ely d ifficu lt or im p ossible in this situation
p arathyroid ectom y, thyroid ectom y, or carotid end arterec- and shou ld be attem p ted only once, if at all, prior to
tom y are at risk for postoperative airw ay com prom ise. tracheostom y.
H oarseness and strid or in the first 48 hou rs after operation Dam age to the recu rrent laryngeal nerve can lead to
can be cau sed by vocal cord ed em a from intubation, p ossi- acu te airw ay com p rom ise. Clinical evid ence of a u nilat-
ble recu rrent laryngeal nerve inju ry, or w ou nd hem atom a. eral recu rrent laryngeal inju ry is su ggested by a w eak,
Sym ptom s of hyp oxia such as restlessness, irritability, and w hisp ery voice (Table 19.3). Voice changes m ight also
som nolence all m ight occu r in the p ostoperative patient for be accom p anied by d ifficu lty w ith com p lete glottic clo-
a variety of reasons bu t shou ld heighten suspicion for a ressu re d u ring cou ghing or Valsalva m aneu ver. Inability to
p iratory problem as part of the d ifferential d iagnosis. close the glottis m ight be exacerbated w ith com bined
Prom pt p hysical exam ination of the patient helps to estab- inju ry to the external branch of the su p erior laryngeal
lish the etiology and severity of airw ay com p rom ise. Pu lse nerve and the recu rrent laryngeal nerve. In isolated recu r-
oxim etry shou ld be p erform ed on all patients w ith resp ira- rent laryngeal nerve inju ry, the intact external branch of
tory d ifficu lties. Patients w ith obvious neck sw elling and the su p erior laryngeal nerve innervates the cricothyroid
com p rom ise d u e to w ou nd hem atom a shou ld have their m u scle to m aintain fu ll ad d u ction of the ip silateral vocal
w ound s op ened im m ed iately, and app ropriate clinical cord . When the su p erior laryngeal nerve is also d am aged ,
m easu res shou ld be taken, inclu d ing evacu ation, reestab- fu ll ad d u ction and glottic closu re is not p ossible, and the
lishm ent of hem ostasis, end otracheal intu bation, and p os- vocal cord is p aralyzed in the interm ed iate p osition, aw ay
sible tracheostom y. The latter can be perform ed at the from the m id line. In m ost instances of isolated recu rrent
bed sid e if necessary (27). laryngeal nerve inju ry, the contralateral vocal cord w ill
Vocal cord ed em a can be d istingu ished from recu rrent m ove across the m id line over a few w eeks tim e to abu t the
laryngeal nerve inju ry by ind irect laryngoscop y u sing a p aralyzed cord . This p rod u ces a relatively norm al voice.
flexible fiberop tic nasop haryngoscope. Mild to m od erate Therefore, it is im p erative to exclu d e occu lt recu rrent
vocal cord ed em a can be m anaged w ith hu m id ification of laryngeal nerve inju ry by p erform ing ind irect laryn-
the insp ired air and close airw ay m onitoring. More severe goscop y p rior to neck op eration in any p atient w ho has
cases m ight requ ire treatm ent w ith steroid s su ch as d exam - had p reviou s neck su rgery, regard less of the qu ality of the
ethasone 10 m g IV every 6 to 12 hou rs or even tra- p atient’s voice (27).
cheostom y p erform ed in the operating room . The u se of If both recu rrent laryngeal nerves are rend ered non-
steroid s is controversial and has only been proven benefi- fu nctional, the vocal cord s w ill becom e p aralyzed in the
cial in p rosp ective rand om ized clinical trials of neonates fu lly ad d u cted p osition. This m ight lead to acu te respira-
and child ren u nd er 5 years old w ho w ere ad ministered d ex- tory com p rom ise. The p atient w ill exp erience d ifficulty
am ethasone 0.25 to 0.5 m g per kg IV prior to planned extu - w ith insp iration, and severe strid or is u su ally evid ent.
bation (28,29). Dexamethasone treated patients had few er Parad oxically, the voice m ight be norm al d u ring this crisis
ep isod es of strid or and reintu bation com p ared to the as the vocal cord s are ap p osed in the m id line. Im m ed iate
control grou p w ho d id not get steroid s. H ow ever, w hen a treatm ent of bilateral recu rrent laryngeal nerve inju ry
involves reintu bation or tracheostom y. Som e patients w ill absorp tion of system ic toxins. Sm oke tend s to be d ry and
have a tem p orary loss of fu nction that recovers over the therefore has a low sp ecific heat even at high tem p eratu res.
next few w eeks (27). Therm al inju ries tend to be lim ited to the airw ay above the
glottis, inclu d ing the nasop harynx, orop harynx, and larynx
(34). Therm al inju ries to the low er resp iratory tract are
■ Tension pneumothorax u nu su al and occu r in situ ations in w hich the sm oke con-
Tension pneu m othorax occurs w hen air enters the potential tains su p erheated p articles or steam (35). Inju ry to the
space betw een the parietal and visceral pleura of the chest u p p er airw ay m u cosa from heat p rod u ces erythem a, u lcer-
and becomes trap ped . The affected lu ng collap ses and su b- ation, and ed em a. H eat d am age to the p harynx can cau se
sequently med iastinal shift occurs. Shift in the med iastinum ed em a severe enou gh to lead to obstruction of the airw ay.
lead s to kinking of the su perior and inferior vena cava w ith Upper airw ay ed em a u su ally occu rs d u ring the first
concomitant impairment in venous return and card iac out- 24 hou rs after therm al inju ry, bu t it can be d elayed in u nre-
put. Ventilation of the contralateral lung is also d iminished , su scitated p atients u ntil flu id ad m inistration is und er w ay.
and high p eak airw ay pressures can be observed . Common When p resent, ed em a u su ally resolves in 2 to 5 d ays (36).
causes of tension pneum othorax includ e traumatic injury, Diagnosis d ep end s on the history and su rveillance p hysi-
spontaneous rupture of a pneumocele, laparoscopy w ith cal exam ination for signs and symp tom s of sm oke exp o-
operation at the esophageal hiatus, and mechanical ventila- su re. Sym p tom s su ch as d ysp nea, strid or, and cyanosis
tion w ith positive end -expiratory pressure (PEEP) (30). shou ld p rom p t early control of the airw ay by end otracheal
Diagnosis of a tension pneumothorax requires timely intu bation. Secu ring of the end otracheal tu be in a burn
clinical assessment. Signs and symptom s that are consistent p atient is of p aram ou nt im p ortance as a d islod ged tube
w ith tension pneumothorax includ e the follow ing: severe m ight be imp ossible to rep lace becau se of u p p er airw ay
respiratory distress, hypotension, unilateral absence of ed em a.
breath sou nd s, neck vein d istention, tracheal d eviation, H yp oxia is p rim arily a resu lt of consu m p tion of oxygen
chest w all crep itu s, and cyanosis. Waiting for a confirm a- by the fire that d rives d ow n the FIO 2 of the am bient air that
tory chest x-ray in the setting of a tension p neu m othorax the victim breathes. Severe hyp oxia lead s to a critical
w ill m ost certainly result in a fatal ou tcom e. Treatm ent is red u ction in the level of oxygen d elivery to the organs
based on the clinical examination. The pleural space shou ld beyond w hich the bod y cannot com p ensate, eventually
be d ecom p ressed w ith a large bore angiocatheter (12 to resu lting in d eath by asp hyxiation. H yp oxem ia can poten-
14G) inserted through the chest w all into the second inter- tiate the toxicity of inhaled carbon m onoxid e and hyd rogen
costal sp ace in the m id clavicular line. This w ill convert the cyanid e (37). H yp oxem ia can also resu lt in an increase in
tension p neu m othorax to a sim ple pneu m othorax. Chest resp iratory rate and m inu te ventilation, thereby m arked ly
d ecom pression shou ld be im m ed iately follow ed by inser- increasing the am ou nt of sm oke subsequ ently inhaled and
tion of a thoracostom y tu be to re-exp and the collap sed w orsening exp osu re to system ic and bronchop u lm onary
lung. Patients w ho are not intu bated and und ergo bilateral toxins (34).
need le thoracostom ies require im m ed iate or sim ultaneous Sm all p articles and toxic gases in sm oke can reach the
airw ay intu bation and p ositive-pressure ventilation. d istal airw ays and alveoli. These com p ou nd s resu lt in
an acu te inflam m atory reaction initially m ed iated by neu -
trop hils (37). Sym p tom s m ight inclu d e p ersistent cou gh-
■ SMOKE INHALATION AND BURNS
ing, bronchorrhea, d ysp nea, and w heezing. Physiologic
Fires in confined spaces can have d evastating conse- changes triggered by the inflam m atory cascad e can resu lt
qu ences, as evid enced by the m ass casu alty event resu lting in w orsened ventilation/ p erfu sion (V/ Q) m atching and
in ap p roxim ately 100 d eaths at a West Warw ick, RI night- increased su scep tibility to p u lm onary infections. Severe
clu b in the w inter of 2003. Most d eaths from a fire scene are cases can p rogress to ARDS. Bronchoscop y in these
d u e to sm oke inhalation inju ry rather than from cu taneou s p atients w ill reveal erythem a, ed em a, and u lcerations of
bu rns and associated com plications (31,32). The p resence the airw ays, often in conju nction w ith carbonaceou s
of inhalation inju ry in association w ith a bu rn increases the sp u tu m (34).
overall m ortality rate and often resu lts in significant p u l-
monary com p lications (33). In a patient w ith a 40% total
bod y su rface area bu rn, the p resence of inhalation inju ry
■ Carbon monoxide poisoning
increases m ortality from 3% to 27%. The sam e p atient has Carbon m onoxid e gas in sm oke can be system ically
over 95% m ortality if he or she is old er than 60. absorbed across the lu ng and have p otentially fatal conse-
qu ences. Carbon m onoxid e bind s to hem oglobin w ith an
affinity 200 tim es greater than oxygen (31). If a su fficient
■ Smoke inhalation am ou nt of circu lating hemoglobin is bou nd to carbon
Sm oke inhalation lead s to inju ry by fou r m echanism s: m onoxid e, tissu e hyp oxia and cell d eath w ill occur. The
d irect therm al inju ry to the airw ays, hypoxia, exp osu re of m ost im m ed iate threat is to oxygen-sensitive organs su ch
the bronchop u lm onary system to toxins, and p u lm onary as the brain. Carboxyhemoglobin (H bCO) levels of 40% to
60% cau se obtu nd ation and loss of consciousness. Levels of carbonaceou s sp u tu m , hoarseness, strid or, and im paired
20% to 40% cau se central nervou s system d ysfunction of consciou sness are all signs and sym ptom s that m ight w ar-
varying d egrees. Interestingly, H bCO levels of 5% to 10% rant fu rther investigation into the p ossibility of inhala-
are fou nd in sm okers and in p eople in urban areas w ho are tional inju ry and trigger p otential intervention. An arterial
exposed to heavy traffic, bu t these levels of carbon m onox- blood gas analysis shou ld be p erform ed and cooxim etry
id e absorp tion are rarely sym p tom atic (31). obtained to evalu ate the level of H bCO in the blood stream .
The diagnosis of carbon monoxide poisoning is based on Patients w ith a high su sp icion for inhalation inju ry or
compatible history and physical examination. Symptoms and evid ence of severe carbon m onoxid e p oisoning shou ld
signs are relatively nonspecific and can include headache, u nd ergo elective orotracheal intu bation to secu re the air-
nausea, malaise, altered cognition, dyspnea, angina, seizures, w ay. In equ ivocal cases, the u se of flexible fiberoptic
card iac arrhythmias, congestive heart failure, and coma (38). nasopharyngeal end oscopy m ight reveal u pper airw ay
Elevated HbCO levels might cause a cherry-red appearance erythem a and soft tissue ed em a that can progress to airw ay
of the skin. This physical find ing is present in only half of com prom ise if left u ntreated .
patients w ith severe carbon monoxide poisoning (31). In car- If severe inju ry to the tracheobronchial tree has
bon monoxide poisoning the blood’s oxygen content is occu rred , the necrotic ep itheliu m of the airw ays w ill
reduced , but the amount of oxygen dissolved in the plasma begin slou ghing arou nd p ostinju ry d ay 3 to 4 (37,40). This
is unaffected by the hemoglobin-bound carbon monoxide. increase in secretions places the patient at risk for airw ay
Arterial blood gas analysis w ill appear normal except for the com p rom ise from obstru ction, d evelop m ent of atelectasis,
HbCO level, w hich requires a cooximeter for measurement. and onset of bacterial p neu m onia. Im p airm ent of pul-
HbCO levels correlate poorly w ith the extent of poisoning m onary host d efense m echanism s, su ch as m u cociliary
(Table 19.4), and d o not pred ict d elayed neurologic sequelae. clearance, fu nction of alveolar m acrop hages, and recru it-
Neurologic deficits, particularly loss of consciousness, m ent of p olym orp honu clear leu kocytes can also increase
w orsen prognosis (39). the risk for p neu m onia (41). Managem ent of the p atient in
Placing the patient w ith carbon m onoxid e p oisoning on this clinical p hase is largely su p p ortive and involves chest
100% oxygen red u ces the half life of carbon m onoxid e in p hysical therap y, p ostu ral d rainage, and bronchoscopy, if
the blood from 4 hours for patients on room air to 1 hou r. necessary, to control secretions. Antibiotics shou ld only be
All patients w ith elevated H bCO levels should receive u sed em p irically w hen bacterial p neu m onia is suspected
100% oxygen u ntil levels of 10% are reached . Given lim - and continu ed only su bsequ ent to confirm atory spu tum or
ited availability and the absence of proven benefit w ithin qu antitative bronchoalveolar lavage cu lture.
the m ed ical literatu re, hyperbaric oxygen (H BO) is consid - Use of heparin and N-acetylcysteine in combination is
ered op tional. Transfer to a bu rn center should not u su ally based on scavenging of the oxygen free radicals produced
be d elayed in favor of H BO treatm ent for carbon m onoxid e when alveolar macrophages are activated by chemicals in
poisoning (38). smoke or compounds in the arachidonic cascade (32). A retro-
All p atients w ith su spected carbon m onoxid e poisoning spective study showed that use of nebulized heparin and
or inhalational inju ry shou ld initially receive hu m id ified N-acetylcysteine to be effective in decreasing mortality, reduc-
100% oxygen by face m ask. Ad d itional evid ence m u st be ing the reintubation rate, and lowering the rate of atelectasis
sou ght on history and p hysical exam ination to confirm su s- in pediatric patients with inhalation injury (42). The Shriners
pected inhalational inju ry. Confinem ent to fire in a closed Hospital for Children in Galveston, TX, utilizes a treatment
space, breathing of large qu antities of sm oke or noxiou s regimen consisting of 5,000 to 10,000 units of heparin in 3 mL
fu m es, singed facial hair, facial burns, perioral soot, normal saline nebulized every 4 hours, alternating with 3 to
5 mL of 20% N-acetylcysteine for 7 days.
Table 1 9 .4 Sign s a n d sym p t om s of ca r bon ■ ASPIRATION PNEUMONIA

m on oxid e p oison in g
Aspiration pneumonia is a pulmonary complication that
Level of Carboxyhemoglobin occu rs follow ing abnormal entry of flu id , particulate matter,
(%HbCO) Signs and Symptoms or gastrointestinal (GI) secretions into the respiratory tract.
20 None, headache, confusion Tw o physiologic requ irem ents are u su ally necessary to pro-
20–40 Disorientation, fatigue, nausea, d uce aspiration pneu monia. First, there mu st be a compro-
visual disturbances mise in the norm al upper airw ay d efenses that protect the
d istal respiratory tree from exposure to noxiou s su bstances.
40–60 Hallucination, combativeness,
coma, shock This can consist of loss of glottic closure, inhibition of cou gh
reflex, and failu re of clearance m echanism s, all of w hich are
60 Death
commonly found in the obtund ed or anesthetized patient.
Adapted from Demling RH. Burn care in the immediate resuscitation period. In:
Second , an inoculation of the low er airw ays w ith d eleteri-
Wilmore DW, Cheung LY, Harken AH, et al, eds. ACS surgery: principles and ous fluid or p articu late matter mu st occu r. This inocu lu m
practice, 2003 ed. New York, NY: WebMD Inc; 2003:52, with permission. can be d etrimental to pulmonary function from d irect toxic
Table 1 9 .5 Con d it ion s t h a t p r ed isp ose t o 24 hou rs (12%), (b) p rom p t resolu tion over 4 to 5 d ays
a sp ira t ion p n eu m on ia (62%), or (c) initial im p rovem ent follow ed by d evelopm ent
of nosocom ial bacterial p neu m onia (26%) (47).
Reduced consciousness The d iagnosis of chem ical p neu m onitis follow ing asp i-
Diminished cough reflex ration is p resu m p tive and is based on clinical su sp icion
Compromised glottic closure and featu res su ch as abru p t onset of severe resp iratory
Neurologic insult sym p tom s w ith significant d ysp nea, low -grad e fever,
Dysphagia cyanosis, d iffu se crackles on au scu ltation, severe hypox-
Disorders of the upper GI tract em ia, and infiltrates on chest x-ray involving d epend ent
Esophageal disease lu ng segm ents. Treatm ent is largely su p p ortive and centers
Surgery of upper airway or esophagus on the p rovision of oxygen, p rotection of the airw ay, and
Gastroesophageal reflux tracheal su ctioning. The acid m aterial is rap id ly neu tral-
Mechanical disruption of glottic closure or esophageal sphincter ized in the lu ng, and d am age is alread y w ell established by
Endotracheal intubation the tim e a p hysician or other healthcare p rofessional
Bronchoscopy becomes aw are of the asp iration event. Anim al stud ies
Upper endoscopy have d em onstrated therapeutic benefit from positive-
Nasoenteric intubation p ressu re ventilation, intravenou s ad m inistration of high
Other m olecu lar w eight colloid s, and infu sion of sod iu m nitro-
Pharyngeal anesthesia p ru ssid e into the p u lm onary artery (48–51). The u sefu lness
Protracted vomiting of m echanical ventilation to su p p ort a p atient w ith acu te
Recumbent position resp iratory failu re is obviou s. H ow ever, recomm end ations
on the u se of the latter tw o therap ies in the treatm ent of
hu m an p atients w ith asp iration rem ain ind eterm inate. The
effect, stim u lation of an inflam m atory process d u e to a large im m ed iate u se of corticosteroid s to treat chem ical p neu-
bacterial bolu s, or creation of airw ay obstru ction from a su f- m onitis follow ing gastric asp iration is u nsu p p orted (52).
ficient volu me of particulate matter (43).
Aspiration pneumonia should be distinguished from
pneumonia itself. Community acquired or nosocomial pneu-
■ Bacterial pneumonia
monia commonly occurs following small volume aspiration Bacterial p neu m onia follow ing asp iration is u su ally cau sed
of microorganisms found in the oral cavity or nasopharynx. by organism s that comm only resid e in the u pper airw ays
The organisms that typically produce pneumonia, such as or stom ach. These bacteria are less viru lent and are prim a-
Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus rily anaerobes that resid e in the gingival creases. Com -
influenzae, and Gram-negative bacilli, are all considered viru- p ared to com m u nity-acqu ired p neu m onia, onset is qu ite
lent bacteria, and only a small inoculum is required . Aspira- slow, w ith p atients m anifesting cou gh, fever, p urulent spu-
tion pneumonia is a term reserved for pulmonary infection tu m , and d ysp nea evolving over a p eriod of several d ays or
and/ or pneumonitis caused by altered clearance mecha- w eeks rather than hou rs (43). The absence of rigors is char-
nisms of less virulent, primarily anaerobic bacteria that con- acteristic of nonp yogenic p neu m onia since p atients w ith
stitute the normal flora of a patient susceptible to aspiration. asp iration p neu m onia from anaerobes alm ost never have
Conditions found in surgical patients that predispose them to shaking chills. Many p atients w ith asp iration pneu m onia
aspiration pneumonia are listed in Table 19.5. d o not p resent acu tely w ith infection. Instead , they present
late w ith com p lications characterized by su p p u ration and
necrosis w ithin the lu ng (53–55). Lu ng abscesses, necrotiz-
■ Chemical pneumonitis ing p neu m onia, or em p yem a all rep resent d elayed presen-
Aspiration of gastric and oropharyngeal contents can tations of u ntreated aspiration p neum onia.
lead to pu lm onary com plications from three m echanism s: Antibiotics are the most important component of treat-
chem ical p neu m onitis, bacterial infection, and m echanical ment for aspiration pneumonia associated with bacterial
obstru ction. The asp iration of 1 to 3 m L/ kg of gastric con- infection. Based on transthoracic culture d ata, a sw itch has
tents w ith a p H 2.5 lead s to rapid pneu monitis character- been mad e from Clind amycin to Piperacillin/ Tazobactam as
ized by atelectasis, peribronchial hem orrhage, pu lm onary the currently the preferred drug for aspiration pneumonia
ed em a, and d am age to bronchial ep ithelial cells (44–46). An w ith or without lung abscess (56). This change is based upon
intense inflam m atory response occu rs, and w ithin 4 hou rs a surprising frequency of the bacteria Klebsiella pneumoniae
the alveoli are filled w ith m arginated p olym orp honu clear found in these aspirates (57). Alternative regimens include
leu kocytes and fibrin. The lung parenchym a eventu ally Ceftriaxone plus Metronid azole or Moxifloxacin (56). When
becom es grossly ed em atous and hem orrhagic w ith loss of nosocom ial pneum onia is suspected , companion aerobic
alveoli and consolid ation. Patients usually follow one of bacteria, particularly Gram-negative bacilli or Staphylococcus
three scenarios after asp iration of gastric contents: (a) rap id aureus, are more important than anaerobes. Therapy should
progressive resp iratory failure resu lting in d eath w ithin therefore be directed at these virulent organisms.
■ Mechanical obstruction 21-fold (65,66). Other significant risk factors for nosocom ial
p neu m onia id entified on m u ltivariate analysis inclu d e the
Aspiration can flood the lu ng w ith flu id and particu late follow ing: age 70 years, chronic lu ng d isease, d epressed
m atter. These m aterials m ight not be intrinsically toxic to consciou sness, large volu m e asp iration, thoracic surgery,
the lu ng, bu t they can cau se acute airw ay obstru ction. Flu - frequ ent ventilator circu it changes, p resence of intracra-
id s that can be asp irated that are not toxic to the lu ng are nial p ressu re m onitor, p resence of nasogastric tu be, H -2
saline, bariu m , m ost ingested fluid s, inclu d ing w ater, and blocker or antacid therap y, transp ort from the ICU to d iag-
gastric contents w ith a p H 2.5. Patients w ho are at risk nostic or therap eu tic p roced u res, p reviou s exp osu re to
for m echanical obstru ction are those w ho cannot p rotect antibiotics, reintu bation, hosp italization d u ring the fall or
their airw ays or cou gh second ary to neurologic d eficit or w inter, and m echanical ventilation for ARDS (66).
im paired consciou sness. The obvious treatm ent is tracheal Increased gastric p H m ay p lay a significant role in elevat-
suctioning and p revention. The m ost im portant preem p - ing the risk for nosocom ial p neu m onia. A rand om ized
tive m easu re in hosp italized patients is to keep the patient controlled trial com p ared three strategies of stress u lcer
in the sem iu p right or up right position (58–60). p rop hylaxis (Ranitid ine, antacid , and Su cralfate) (67). The
Solid objects su ch as peanu ts, vegetable particles, sm all incid ence of ventilator-associated p neu m onia w as signifi-
p arts, and teeth can becom e aspirated and lod ged in the cantly low er w ith Su cralfate (5%) than w ith antacid s (16%)
airw ay (43). Foreign bod y asp iration is m ore com m on and Ranitid ine (21%). Su p ine p ositioning can p red isp ose
am ong you ng child ren, and plant prod u cts are problem atic p atients to m icroasp iration and d evelop m ent of nosoco-
becau se they cannot be visu alized on chest x-ray. For large m ial p neu m onia. A rand om ized trial of p ositioning in 90
objects that becom e lod ged in the larynx or trachea, su d d en intu bated p atients w as term inated early w hen interim
respiratory d istress w ith cyanosis, strid or, and aphonia can analysis revealed a significantly low er incid ence of noso-
ensue. Treatm ent consists of the H eim lich m aneu ver w ith com ial p neu m onia in the sem irecu m bent versu s su p ine
firm rapid pressu re applied to the u pper abd om en in an p atients (5% vs. 23%) (60).
attem p t to force the d iap hragm up w ard , generating Preventive measures for which there is now support in
enough p ressu re to d islod ge the particle. Sm aller particles the literature include avoid ance of acid-blocking med ications
w ill becom e lod ged in the m ore d istal portions of the train patients not at high risk of developing a stress ulcer or
cheal-bronchial tree. These patients present w ith cou gh, stress gastritis, selective decontamination of the GI tract,
and chest x-ray d em onstrates atelectasis or obstru ctive decontamination of the oropharynx, and patient positioning
em p hysem a w ith card iac shift and elevated d iap hragm . with the head-of-bed at 30 to 45 degrees (62,66). Tw o other
Unilateral w heezing m ight be appreciated if there is partial potential preventive measures are subglottic drainage and
obstruction. The p rim ary intervention is therapeu tic rigid silver-coated endotracheal tubes. These two items require
or fiberop tic bronchoscop y perform ed to rem ove the special equipment and replacing of the existing endotracheal
obstructive elem ent (61). that hind ers their w id espread acceptance; however, the evi-
dence for these tw o mod alities to red uce the frequency of
■ NOSOCOMIAL PNEUMONIA ventilator-associated pneumonia exists. Daily interruption of
sedative infusions and evaluation of patient’s mental status
N osocom ial p neu m onia is d efined as p neu m onia occu r- as well as physiologic suitability for extubation is associated
ring 48 hou rs after ad m ission to the hosp ital and exclu d - with a reduction in complications associated with mechani-
ing any infection that is p resent or incu bating at the tim e cal ventilation, one of which is ventilator-associated pneumo-
of ad m ission (62). Ventilator-associated p neu m onia is a nia (62,68). Avoidance of unnecessary use of chemical
sp ecific form of nosocom ial p neu m onia that refers to the paralytic agents is also recommend ed as they suppress the
d evelop m ent of bacterial p neu m onia in p atients w ith patient’s ability to cough and clear secretions (62). Use of
acu te resp iratory failu re w ho have been receiving m echan- haloperidol to manage agitation in mechanically ventilated
ical ventilation for more than 48 to 72 hou rs (62). Patients in patients has been show n to result in significantly low er hos-
the surgical intensive care unit (ICU) have higher rates of pital mortality when compared to patients who d id not
nosocom ial p neu m onia than in the m ed ical ICU (63). Data receive haloperidol (21% vs. 36%) (69).
from the N ational N osocom ial Infection Su rveillance sys- N osocomial pneu m onias are caused by a w id e-
tem show s that the four types of ICUs w ith the highest inci- sp ectru m of bacterial p athogens. They are frequently
d ence of ventilator-associated p neu m onia all care for p olym icrobial in origin and are rarely d u e to viral or fungal
surgical p atients: bu rn, neurosurgical, traum a, and su rgical microbes in an im m u nocom p etent p atient (62). Com m on
ICUs, in d ecreasing ord er of incid ence (64). microbial pathogens id entified on cultu re inclu d e Gram -
negative bacilli su ch as Pseudomonas aeruginosa, Escherichia
coli, Klebsiella pneumoniae, Enterobacter sp ecies, and Acineto-
■ Risk factors, etiology, and prevention bacter sp ecies (62,70). Infections d u e to Gram -positive
The lead ing risk factor for nosocom ial pneu monia is organism s inclu d e Staphylococcus aureus and in p articular
m echanical ventilation. End otracheal intubation increases m ethicillin-resistant S. aureus (MRSA) as w ell as and Strep-
the risk of nosocom ial p neum onia betw een 6-fold and tococcus sp ecies. Each sep arate ICU has its ow n intrinsic
flora and might have other viru lent bacterial organism s im pacts heavily on the organism that is the m ost likely
that are high in p revalence for nosocom ial pneu m onia. It is cu lp rit for nosocom ial p neu m onia—for exam ple, trau m a
therefore of critical im p ortance to know the offend ing p atients: asp iration, oral flora typ e organism s; burn
pathogens in the ICU in w hich one practices w hen choos- p atients: Staphylococcus aureus; general su rgery patients:
ing em p iric antibiotic therapy for patients w ith su spected viru lent Gram -negative bacilli. In the absence of positive
nosocom ial pneum onia. m icrobial cu ltu re d ata, p atients w ith three of the five clini-
cal signs and sym p tom s of p neu m onia shou ld be p laced on
em piric antibiotic therapy and a low er respiratory tract
■ Diagnosis and treatment sam p le for cu ltu re p rom p tly obtained .
Accu rate d iagnosis of pneu monia rem ains elusive. Clinical Fou r questions are vital in choosing the appropriate
signs and sym p tom s su ggestive of p neu m onia inclu d e new em piric antibiotic therapy for each ind ivid u al hospital,
or p rogressive infiltrate on chest x-ray, fever, w hite blood ICU, and p atient (79):
cell (WBC) cou nt greater than 10,000 per m m 3, p u ru lent
spu tu m , and increasing oxygen requirem ents (71). Pres-
■ Is the patient at risk for m ethicillin-resistant Staphylococ-
ence of p ositive find ings for three or more of these signs cus aureus (MRSA)?
and sym p tom s shou ld trigger the obtaining of a sp u tu m
■ Is Acinetobacter baumannii a p roblem in the institu tion?
sam p le for Gram stain and confirm atory bacterial cu ltu re
■ Is the patient at risk for Pseudomonas aeruginosa infection?
follow ed by em p iric ad m inistration of antibiotics. Tracheal
■ Is the patient at risk for m ultid ru g resistance Gram -
asp irate, p rotected specim en bru sh, or bronchoalveolar negative organism s?
lavage can be used to obtain spu tum sam ples for cu lture. At a bare m inim u m, the em p iric antibiotic regim en
Qu antitative bronchoscop ic sp ecim ens are m ore accu rate chosen shou ld have activity against Enterobacter sp ecies,
in confirm ing the d iagnosis bu t have the d isad vantage of Klebsiella sp ecies, E. coli, Proteus sp ecies, Serratia marcescens,
being tim e-consuming and expensive. A prospective ran- Haemophilus influenzae, m ethicillin-sensitive Staphylococcus
domized clinical stu d y evalu ated w hether an invasive test aureus, and Streptococcus pneumoniae (62). Patients w ho
u sing protected bru sh specim ens or bronchoalveolar have asp irated , w ho have u nd erlying m ed ical cond itions
lavage w as su p erior to clinical criteria in 431 patients w ith su ch as recent abd ominal su rgery, com a, head traum a, d ia-
su sp icion of ventilator-associated p neum onia (72). Patients betes m ellitu s, renal failu re, or COPD, are being treated
w ho u nd erw ent invasive testing had a significantly low er w ith steroid s or antibiotics, or w ho have a p rolonged ICU
14-d ay m ortality rate (16% vs. 26%). This su rvival ad van- stay m ight requ ire ad d itional coverage for anaerobes,
tage remained at d ay 28 and w as also associated w ith an MRSA, and Legionella. Coverage for Pseudomonas aerugi-
increase in antibiotic-free d ays as w ell as a low er m ean nosa and m u ltid ru g resistant Gram -negative bacilli su ch as
nu m ber of antibiotics ad m inistered . Operator variability Acinetobacter baumannii should also be consid ered in criti-
and d ifferences betw een ICUs m ake it d ifficult to u niver- cally ill p atients receiving antibiotics p rior to the onset of
sally rep licate and apply these resu lts. Also, the threshold p neu m onia and in institu tions in w hich these bacteria are
for a p ositive qu antitative bronchoalveolar lavage cu ltu re comm on p athogens.
varies betw een 104 and 105 cfu / m L in p u blished stu d ies. If MRSA is a frequ ent nosocom ial pathogen in the insti-
H ow ever, there is a d efinite trend in the literatu re tow ard tu tion, Vancom ycin or Linezolid w ill be a necessary first
utilizing bronchoalveolar lavage to im prove the accu racy choice for em p iric Staphylococcal coverage, bu t it shou ld be
of p neu m onia d iagnosis and to d ecrease p neu m onia treat- d iscontinu ed if MRSA is not isolated on cu ltu re. The litera-
ment costs through the red uction of false-positive cu ltures ture supp orts em piric m onotherapy w ith third -generation
(71,73–75). cephalosp orins w ith antip seu d om onal activity, but cau tion
Becau se d efinitive d iagnosis is d ifficu lt, m any p atients is su ggested as m onotherapy has been associated w ith the
are incorrectly su spected of having pneu m onia. This error d evelop m ent of resistant strains in d ocu m ented cases of
can lead to overtreatm ent from em piric antibiotic therap y Pseudomonas aeruginosa infection (80). Com bination ther-
w ith all of its risks for su p erinfection and antibiotic toxicity. apy is associated w ith a su rvival benefit com pared to
Conversely, it has been established that inad equ ate antibi- m onotherap y in p atients w ith p seu d om onal p neu m onia
otic therap y significantly affects m ortality from infections and bacterem ia (81).
and is an im p ortant ind epend ent pred ictor of hosp ital m or- A current em piric antibiotic strategy for nosocom ial
tality w ith an OR of 4.3 (76,77). Inad equate initial antibiotic p neu m onia em p loyed in ou r su rgical, trau m a, and bu rn
selection is associated w ith a significant increase in ventila- ICU follow s:
tor-associated p neum onia mortality (37% vs. 15%) com -
pared to ad equ ate initial therapy (78). The choice of p rop er ■ Intubated patients susp ected of having nosocom ial
antibiotic treatm ent for nosocom ial p neum onia shou ld be p neum onia are id entified by having three of five clinical
gu id ed by recent antibiotic therapy, the ind igenou s bacter- criteria for p neu m onia (new or p rogressive infiltrate on
ial flora of the hospital and ICU, the presence of u nd erlying chest x-ray, fever, elevated WBC cou nt 10,000/ m m 3,
d iseases, the typ e of patient (e.g., traum a, bu rn, general p u ru lent sp u tu m , and increasing oxygen requ irem ents).
surgery), and the available culture d ata. The type of p atient ■ Perform qu antitative bronchoalveolar lavage.
■ Initiate em piric antibiotic therap y w ith one of the follow - ■ ACUTE RESPIRATORY DISTRESS SYNDROME
ing antibiotic com binations based on p atients m ed ical
com orbid ities: ARDS refers to patients w ith acute and progressive respira-
■ If 4 d ays on the m echanical ventilator or patient tory d isease of a noncardiac nature, in association w ith dif-
has been hosp italized , start Vancom ycin, Piperacillin/ fuse, bilateral pulmonary infiltrates d emonstrated on chest
Tazobactam , and Tobram ycin. If am inoglycosid e con- x-rays, and w ith hypoxem ia (84). ALI and its more severe
traind icated replace w ith Levofloxacin. form, know n as ARDS, are clinical syndromes pathologi-
■ If 4 d ays on the m echanical ventilator, consid er cally characterized by acute and persistent pulmonary
m onotherap y for asp iration-typ e organism s w ith inflammation w ith increased vascular permeability. In 1994,
Ceftriaxone, Am picillin/ Su lbactam , or Piperacillin/ the American-European Consensus Conference on ARDS
Tazobactam . established w ritten clinical d efinitions of ALI and ARDS,
■ If the qu antitative bronchoalveolar lavage cultu re resu lts w hich are listed in Table 19.6 (85). In recent years, significant
are 104 cfu / m L, continu e antibiotics and tailor cover- ad vances in und erstand ing of the pathophysiology of ARDS
age based on organism and sensitivities. and lung injury have been mad e, lead ing to prospective ran-
■ If the qu antitative bronchoalveolar lavage cultu re resu lts d omized clinical trials and attempts to improve therapy on
are 104 cfu / m L, d iscontinue antibiotic therapy. the basis of scientific know ledge. Despite these recent
ad vances, the mortality from severe ARDS remains high—
The American Thoracic Society (ATS)/ Infectious Diseases betw een 40% and 50% in both ad ults and child ren (86,87).
Society of America guidelines for the management of ventila- The pathophysiology of ARDS is complex but can be
tor-associated or hospital-acquired pneumonia are also an sum m arized as m assive capillary leak that is the resu lt of an
excellent resource for guidance of empiric antibiotic therapy excessive inflammatory response in the host’s lung tissue.
and can be accessed through the ATS w eb site at ww w. ARDS has a rapid onset over 4 to 48 hours and can persist
thoracic.org/ sections/ publications/ statements/ index.html. for d ays to w eeks. ARDS progresses through four d istinct
Previou sly, exp erts have recom m end ed long courses (14 clinical phases. Phase one is the initial prod rome that is
to 21 d ays) of antibiotic treatment for nosocom ial pneu m o- characterized by d yspnea, tachypnea, and a respiratory
nia. Recent p rosp ective rand om ized stud ies on this su bject alkalosis w ith a normal Pa O 2. This p hase is d riven by
have begu n to challenge this d ogm a. In a large Europ ean inflammatory med iators and activation of inflammatory
stud y of 401 p atients d iagnosed w ith ventilator-associated cells su ch as alveolar macrop hages. Phase tw o is marked by
pneu m onia by qu antitative bronchoalveolar lavage cu l- the onset of lu ng inju ry in the first 24 hou rs. This results in
ture, 197 p atients w ere rand om ly assigned to receive 8 d ays the clinical find ings of hypoxem ia and rad iographic evi-
of antibiotic therap y, and 204 to receive 15 d ays of antibi- d ence of scattered pulmonary infiltrates bilaterally. During
otic treatm ent (82). Prim ary ou tcom e m easu res w ere m or- this tim e, increased p ulm onary capillary p erm eability lead s
tality, recu rrence of pneum onia, and antibiotic-free d ays. to interstitial ed em a, neutrophil m argination, and an inter-
Patients treated for 8 d ays had no excess m ortality (18.8% stitial inflam m atory response. This p rocess ultim ately
vs. 17.2%). It has been ou r practice to treat chrom osom ally causes a severe loss of alveolar units in the patient. The third
m ed iated resistance-p rone bacteria su ch as Acinetobacter p hase resu lts in p rogressive lu ng injury. Injury is evid enced
species, Pseudomonas aeruginosa, Enterobacter species, Serra- by increased shu nt fraction and severe hyp oxemia. The pul-
tia species, and Citrobacter species for a m inim u m of monary parenchyma und ergoes microvascular thrombosis,
10 d ays. Pseudomonas aeruginosa, Enterobacter species, and red istribution of p ulm onary blood flow, and increasing
Acinetobacter species are know n to be highly resistant and
therefore com m only receive d ouble coverage w ith tw o
antibiotics. H ow ever, there is not conclusive evid ence to Table 1 9 .6 D efi n it ion of a cu t e lu n g in ju r y a n d
support combination therap y for nosocom ial pneum onia a cu t e r esp ira t or y d ist r ess syn d rom e
d u e to these Gram -negative pathogens. A large rand om - (ARD S) (75)
ized clinical trial su ggests that m onotherap y of ventilator- Acute lung injury
associated p neu m onia is as effective as com bination Acute onset of pulmonary failure
therap y w ith there being no d ifference in 28-d ay m ortality PaO2/FiO2 Ratio 300 mm Hga
betw een grou p s (83). For pneum onia as a result of resistant Bilateral infiltrates on chest x-ray
Staphylococcus aureus, Pseudomonas aeruginosa, or Acineto- Pulmonary capillary wedge pressure 18 mm Hg
bacter sp ecies rep eat qu antitative bronchoalveolar lavage Acute respiratory distress syndrome
cu lture is p erform ed at 6 d ays and if lavage cu lture resu lts All of criteria for acute lung injury
are 104 cfu / m L, antibiotics are continu ed to com p lete a PaO2/FiO2 Ratio 200 mm Hga
full 15 d ay cou rse of treatm ent. Patients su spected of hav- a
Regardless of the level of positive end-expiratory pressure (PEEP).
ing anaerobic bacterial pneu m onia should also be placed
Adapted from Bernard GR, Artigas A, Brigham KL, et al. The consensus committee
on Clind am ycin or Flagyl em pirically. The selection of report of the American-European consensus conference on ARDS: definitions,
em piric antibiotic therapy m u st take into account patient mechanisms, relevant outcomes and clinical trial coordination. Intensive Care
d ata and shou ld be institu tion-sp ecific. Med 1994;20:225–232, with permission.
ed em a of the alveolar cap illary m em branes. Du ring the gies to reduce iatrogenic lung injury and exacerbation of
fourth and final phase, the inflammatory response sw itches pulmonary failure in surgical patients at increased risk. Treat-
from acute to chronic and is associated w ith ongoing ment of ARDS is focused on eliminating the inciting source,
inflam m ation and pu lm onary fibrosis. Macrop hages and utilizing protective ventilator strategies to minimize ventila-
progressive interstitial fibrosis that can become irreversible tor-ind uced lung injury, avoidance of additional organ
d ominates the inflamm atory response (88,89). failure, and provision of adequate nutrition. Failing all
Basic scientific advances have improved our understand- other therapies, extracorporeal life support (ECLS) may be
ing of the pathophysiology of ARDS, and therapeutic options employed in rare circumstances for severe ARDS patients.
are emerging to treat the excessive inflammatory response of The d iagnosis of ARDS is based on find ings of acu te
early ARDS and the irreversible fibroproliferative response of onset of severe hyp oxem ia (Pa O 2 200 m m H g) and bilat-
late ARDS (88). Identification of risk factors for ARDS has eral infiltrates on chest x-ray (Fig. 19.1) in the absence of
allowed early implementation of alternative ventilator strate- p u lm onary ed em a. In som e clinical situ ations, it m ight
A B
C D
FIGURE 19.1. Common radiologic features of acute respiratory distress syndrome (ARDS). All chest x-rays are portable anteroposterior
projection. A: 40-year-old man with diabetic ketoacidosis and right lower lobe infiltrate from streptococcal pneumonia. B: Same man 1 day
later with severe bilateral blossoming of pulmonary infiltrates. C: 49-year-old woman with staphylococcal sepsis and bilateral ground glass
pulmonary infiltrates. Note the presence of air bronchograms. D: 36-year-old man with blastomycosis pneumonia and dense patchy infil-
trates bilaterally. This patient required extracorporeal life support for 16 days and was discharged to rehabilitation on hospital day 32.
becom e necessary to p lace a Sw an-Ganz catheter into the m u lticenter, rand om ized , controlled stu d y that com pared a
p ulmonary artery to verify that the pulm onary cap illary VT of 6 m L/ kg id eal bod y w eight (and p lateau pressure
w ed ge pressu re (PCWP) is 18 m m H g in ord er to ru le ou t 30 cm H 2O) w ith a VT of 12 m L/ kg id eal bod y w eight
p ulmonary ed em a as the etiology of acute respiratory fail- (and p lateau p ressu re 50 cm H 2O). The trial show ed a sig-
u re. The p resence of a PCWP 18 m m H g favors ALI or nificantly low er m ortality, 31% versu s 40%, in the low -VT
ARDS over hem od ynam ic pu lm onary ed em a. H ow ever, an grou p . The nu m ber of ventilator-free d ays in the first
elevated PCWP d oes not exclud e ARDS. If pu lm onary infil- 28 d ays w as significantly higher in the grou p treated w ith
trates on chest x-ray and hypoxem ia d o not im prove w ithin low er VTs (12 vs. 10) as w as the nu m ber of d ays w ithout
24 to 48 hou rs follow ing norm alization of PCWP, ALI or failu re of nonp u lm onary organs or system s (15 vs. 12). In
ARDS has most likely occu rred sim u ltaneously w ith hem o- p atients w ith ALI and ARDS, high levels of p lasm a inter-
d ynam ic p u lm onary ed ema (90). leu kin-6 and -8 are associated w ith increased m orbid ity
and m ortality. Low er VT ventilation in the ARDS N etw ork
■ Low tidal volume ventilation and p rosp ective rand om ized trial w as also associated w ith a
m ore rap id attenu ation of the inflam m atory resp onse (97).
permissive hypercapnia
Mechanical ventilatory strategies to red u ce VTs and
Management of mechanical ventilation for patients with alveolar overd istension can resu lt in inad equ ate lu ng ven-
ARDS involves und erstand ing how to minim ize and pre- tilation. Perm issive hyp ercap nia is a consequ ence of a ven-
vent ventilator-ind uced lung injury. Webb and Tierney (91) tilator strategy that accepts d eliberate hypoventilation in
first d emonstrated ventilator-induced lung injury in animals an effort to red u ce p u lmonary overd istention and high
in 1974, w hen they revealed the detrimental effects of venti- transalveolar p ressu res w ithin the com p liant noncollap sed
lation at a peak inspiratory pressure of 45 cm H 2O in rats. lu ng in p atients w ith ARDS. This techniqu e ind u ces the
Subsequently, investigators have d ocumented an increase in sid e effect of hyp ercarbia and resp iratory acid osis w hich
pulmonary edema and histopathology in rats ventilated at a are m anaged med ically. The VT is grad u ally red u ced to
peak inspiratory pressure of 45 cm H 2O for only 5 to 20 min- allow a p rogressive rise in the Pa CO 2 to levels as high as
utes (92). Healthy sheep, when mechanically ventilated at a 120 mm Hg while the blood pH is maintained above 7.1 to 7.2
peak inspiratory pressure as low as 30 to 40 cm H 2O, showed by the intravenous administration of buffer solutions (98).
an increase in wet-to-dry lung weight, deterioration in gas Mortality in ad u lts w as red u ced to 26% com p ared to the
exchange, an increase in the surface tension of lung lavage exp ected m ortality of 53% based on an Acu te Physiology
fluid, and lung lesions consistent with ARDS (93). and Chronic H ealth Evalu ation (APACH E) II score w hen
The u se of high tid al volum es (VT) and / or high ventila- low -volu m e, p ressu re-lim ited ventilation w ith p erm issive
tor pressures in an attem pt to ventilate the patient w ith hyp ercap nia w as ap p lied to p atients w ith ARDS (99).
w orsening resp iratory failu re can resu lt in com p rom ise of When im p lem enting p erm issive hyp ercap nia, the p rogres-
card iop u lm onary fu nction and the d evelop m ent of ventila- sive rise in Pa CO 2 shou ld not exceed 10 m m H g/ hou r and
tor ind u ced lu ng inju ry. There is evid ence that alveolar only rarely shou ld the m axim u m level exceed 80 to 100 m m
stretch ind uced by large insp ired VTs p lays a significant H g. Patients m ight requ ire heavy sed ation and even chem -
role in the d evelop m ent of ventilator-ind uced lung inju ry ical p aralysis to overcom e the hyp ercap nic resp iratory
through the incitem ent of an exaggerated alveolar inflam - d rive and avoid d iscom fort. Potential d eleteriou s effects of
m atory resp onse w hich is associated w ith system ic inflam - hyp ercap nia includ e elevation in intracranial p ressu re in
m ation as w ell (94). In ARDS, large proportions of the lu ng p atients w ith brain inju ry, m ild hyp ertension, increased
alveoli becom e consolid ated and are not available for gas card iac ou tp u t, and increased p u lm onary vascu lar resist-
exchange. The resu lting available lu ng units are sm all in ance (88). A second ary analysis of the ARDS N etw ork low
nu m ber and give the p atient a fu nctional lu ng that is anal- VT multicenter trial (n 861) d ocumented that hypercapnic
ogous to a “baby lu ng” in size. Attempting to force ad u lt acid osis w as associated w ith a red u ced 28-d ay mortality
m agnitu d e VT breaths into this “baby lu ng” can result in (ad ju sted od d s ratio 0.14, 95% CI 0.03–0.70) in the 12 m L/
overd istention of the rem aining open alveoli and high d is- kg pred icted bod y w eight VT grou p after controlling for
tend ing p ressu res. This alveolar overinflation can exacer- com orbid ities and severity of lung inju ry, bu t no d ifference
bate existing lung injury lead ing to m icrovascu lar injury w as id entified in the 6 m L/ kg VT grou p (100). These resu lts
and w orsening p u lm onary ed em a (95). are consistent w ith a p rotective effect of hyp ercap nic acid o-
Using a low -VT (6 m L/ kg) approach to m echanical ven- sis against ventilator-ind u ced lung inju ry that w as not
tilation in anim als w ith Pseudomonas aeruginosa ind u ced fou nd w hen the fu rther ongoing inju ry w as red u ced by
ALI resu lted in enhanced oxygenation, increased arterial 6 m L/ kg p red icted bod y w eight VTs.
blood p H , increased blood pressu re, and a d ecrease in
extravascular lung w ater w hen com pared to a high-VT
group (15 m L/ kg) (96). The ARDS N etw ork trial conclu -
■ Pressure control and inverse ratio ventilation
sively d em onstrated the clinical valu e of a low -VT versu s Conventional ventilation involves volu m e cycling w ith
high-VT ap p roach in the m echanical ventilatory su pp ort of VTs in the 10 to 15 m L/ kg range. An alternative m od e
patients w ith severe respiratory failure (86). This trial w as a of ventilation u sed in ARDS patients is pressu re control
ventilation. In this mod e the target peak and plateau airw ay 6 m L/ kg, avoid ing high p lateau airw ay p ressures 30 to
pressu re is kept 30 to 35 cm H 2O by feed back servo regu - 35 cm H 2O, u tilizing p erm issive hyp ercap nia, and the step -
lation of the ventilator flow rate. The pressu re versus tim e w ise u se of p ressu re-lim ited m od es of ventilation (102). A
curve for a breath in pressure control ventilation resembles stu d y of this strategy show ed an im p roved su rvival at
a square w ave in w hich a u niform p ressure is generated 28 d ays (62% vs. 29%), a higher rate of w eaning from
throughou t the inspiratory cycle. This resu lts in noticeably m echanical ventilation, and a low er rate of barotrau m a in
smaller VTs (4 to 8 m L/ kg) w ith each breath and possible the p atient grou p that received the p rotective lu ng strategy
hypercapnia, especially in stiff noncompliant lungs. The VT or “op en lu ng” ap p roach com p ared to controls (103). There
generated w ill vary consid erably w ith changes in compli- w as, how ever, no d ifference in the in-hosp ital m ortality for
ance, and rapid d ecreases in comp liance can lead to inad e- these p atients. The low 28-d ay su rvival in the control
qu ate ventilation. Use of pressure control ventilation allow s grou p has raised qu estions abou t this trial’s valid ity. In the
tight control of airw ay pressures, minimization of baro- N ational Institu tes of H ealth (N IH ) ARDS N etw ork trial of
trauma, and enhanced recruitment of collapsed alveoli low VTs (6 m L/ kg) com p ared to trad itional VTs (12 m L/ kg)
throughout the inspiratory cycle. for mechanical ventilation in ARDS, m ortality w as signifi-
The norm al insp iratory to expiratory ratio is 1:3 or 1:4. cantly low er in the grou p treated w ith low er VTs than in the
By lengthening the tim e of the insp iratory p hase, one group w ith trad itional VTs (31% vs. 40%) (86). The m ean
increases the tim e available for gas exchange and p oten- p lateau p ressu res w ere 25 6 and 33 8 cm H 2O, respec-
tially inflates collapsed alveoli. In some instances, it is nec- tively. A red u ction of 25% in the m ortality of these p atients
essary to invert this ratio so that m ore tim e is sp ent d u ring w ith low er VTs offers strong evid ence for a p rotective lung
insp iration than expiration—so-called inverse ratio venti- strategy approach to m echanical ventilation in patients
lation. Inverse ratio ventilation allow s for less tim e for w ith ARDS.
recru ited alveoli to collapse d u ring expiration. As long as Based on the ARDS N etw ork trials and others d etailing
there is ad equ ate tim e for CO 2 clearance, m ean airw ay the “open lu ng” approach, m ost clinicians tod ay avoid high
pressu re is m onitored , and the patient is app rop riately p lateau pressures, u se low -VTs, and apply appropriate lev-
sed ated to overcom e the u nnatu ral breathing p attern p ro- els of PEEP to encourage lung recruitment and avoid cycli-
vid ed by this m od e of ventilation, it can be a safe and effec- cal atelectasis. H ow ever, the extent to w hich VTs and
tive w ay of increasing oxygenation and recru iting FRC in inspiratory airw ay pressures should be red uced to optimize
severe resp iratory failu re. Pressu re control ventilation and clinical outcomes is a controversial topic. A recent stud y
pressu re control-inverse ratio ventilation are stand ard exam ined all patients w ith p lateau pressu res in the ARDS
techniqu es u sed in neonatal m echanical ventilation. N etw ork low er VT trial (104). Figu re 19.2 d emonstrates the
relationship of m ortality versu s P plat for all patients and
show s d ecreasing mortality as Day 1 P plat d eclines from high
■ Open lung approach to low levels. It d oes not reveal a safe P plat threshold w ithin
One of the m ore com m on m eans of recru iting collap sed the range of Day 1 P plat levels measured in patients w ith
alveoli an d in creasing FRC is to u se PEEP. By n ot allow - ALI/ ARDS. Bivariate analysis also d em onstrated that
ing all the p ressu re in the lu ng to escap e d u ring exp ira- low er P plat quartiles w ere associated w ith red uced mortality
tion, alveoli that are u nstable and p rone to collap se w hen compared w ith higher P plat quartiles.
cannot d o so. This techniqu e can be thou ght of as hold ing In the French led “Exp ress trial,” u se of an approach to
the lu ng p artially op en so that the next breath is not start- set PEEP at a level to reach a p lateau p ressu re of 28 to 30 cm
ing from total collap se in a noncom p liant lu ng. The op ti- H 2O (increased recruitm ent strategy) d id not red u ce m or-
m al level of PEEP to u se in ARDS p atients is d ifficu lt to tality, bu t d id im p rove lu ng fu nction, red u ced the d u ration
d eterm ine, bu t evid ence is em erging to su ggest th at op ti- of mechanical ventilation, and the d u ration of organ failu re
m al recru itm en t and m ain tenance of lu ng volu m e occu rs w hen com p ared to p atients assigned to a m od erate PEEP
w h en PEEP is set at a valu e th at m atches or exceed s the strategy (5–9 cm H 2O, m inim al d istension strategy) (105).
low er inflection p oint (P flex) on th e insp iratory static p res- An “op en lu ng” ap p roach that com p ared target VTs of
su re-volu m e cu rve (101). A single breath com p liance 6 m L/ kg, p lateau p ressu re 30 cm H 2O, and conventional
cu rve w ith VT p lotted against static airw ay p ressu re w ill levels of PEEP w ith an exp erim ental strategy of target VTs
d em onstrate tw o inflection p oints. The low er one rep re- of 6 m L/ kg, p lateau p ressu re 40 cm H 2O, recru itm ent
sents the theoretical critical op ening p ressu re of m ost m aneu vers, and higher levels of PEEP show ed no d iffer-
alveoli available for recru itm ent, and the u p p er p oint ence in m ortality rate (36% vs. 40%) (106). This open lu ng
rep resents the loss of elastic p rop erties of the lu ng sec- ap p roach d id resu lt in ap p arent im p rovem ents w ithin the
on d ary to overd istension (88). second ary end p oints of hyp oxem ia and u se of rescu e ther-
The com bination of PEEP to recruit FRC and p ressu re ap ies. In conclu sion, one shou ld u se a volu me or pressu re
control ventilation to m inim ize barotrau m a has been su p p ort ventilator m od e that keep s the VT near 6 m L/ kg,
term ed the “open lu ng” approach (102,103). This strategy lim its the plateau pressure to as low a level as p ossible to
involves m aintaining the PEEP above the low er inflection m aintain ventilation, and m akes ap p rop riate use of PEEP
point of the p ressu re-volu me cu rve, keeping the VT to recru it FRC.
FIGURE 19.2. Mortality difference

by quartile of Day 1 Pplat. The range of
Pplat levels in cm H2O and the number
of patients (n) is detailed in each bar
of the graph. ARR, absolute risk
reduction; CI, confidence interval.
(From Hager DN, Krishnan JA, Hay-
den DL, et al. Tidal volume reduction
in patients with acute lung injury
when plateau pressures are not high.
Am J Respir Crit Care Med 2005;172:
1241–1245, with permission.)
■ Airway pressure release ventilation op en-lu ng ventilation. Althou gh recru itm ent m aneuvers
m ay be effective in im p roving gas exchange and com p li-
Airw ay pressu re release ventilation (APRV) is a pressure ance, these effects m ay not be su stained and m ay requ ire
lim ited , time-cycled m od e of m echanical ventilation that rep eated m aneu vers. APRV m ay be view ed as a nearly con-
allow s a p atient u nrestricted spontaneous breathing d u r- tinu ou s recru itm ent m aneu ver w ith P H p rovid ing 80% to
ing the ap p lication of continu ou s p ositive airw ay p ressu re 95% of the cycle tim e creating a stabilized “op en lung”
(P-H igh, P H ) (Fig. 19.3). It is an alternative approach to w hile facilitating sp ontaneou s breathing. The ventilator
FIGURE 19.3. Example of gas flow and airway pressure for airway pressure release ventilation or BiLevel ventilation mode. This mode
maintains a high airway pressure (Phigh) with intermittent release periods to a low pressure analogous to positive end-expiratory pressure
(Plow). Patients who are not chemically paralyzed can take spontaneous breaths during the Thigh phase that allow additional pressure sup-
port. The clinician sets the high and low pressure settings, number of breaths, and the release time (Tlow). This mode provides increased
inspiratory time to allow for gas exchange and alveolar recruitment, avoidance of alveolar derecruitment, and the ability to improve
hemodynamics by allowing the patient to breathe spontaneously.
maintains a high-pressu re setting (P H ) for the bu lk of the occu rring in the first hou r of p ronation (109). Prone posi-
resp iratory cycle w hich is follow ed by a period ic release to tioning, althou gh not associated w ith a significant su rvival
a low -p ressu re setting (P L) analogous to PEEP. Patients ad vantage, m ay serve a role as rescu e therap y for patients
(w ho are not receiving neu rom u scu lar blockad e) can sp on- w ith ARDS and refractory life-threatening hyp oxem ia.
taneou sly breathe on top of this form of continu ous posi-
tive airw ay p ressu re, w hich is period ically low ered to
allow ventilation and CO 2 clearance. The spontaneou s
■ Corticosteroids
breathing allow ed d uring APRV can d ecrease intrathoracic Prior stu d ies have suggested a benefit for the use of corti-
pressu re as insp iration by the patient resu lts in p eriod ic costeroid s in refractory d isease, or the late, fibroprolifera-
cycles of negative p ressu re from d iap hragm and chest w all tive stage of ARDS (88). The m echanism of action for the
excu rsion. APRV is no d ifferent than pressure-controlled steroid effect on the fibroproliferative response seem s to
inverse ratio m echanical ventilation in p atients receiving involve m od u lation of m acrop hage and fibroblast activity
neu rom u scu lar blockad e. To d ate, an ad equately d esigned that can lead to irreversible p u lm onary fibrosis. In a ran-
and p ow ered stu d y to d emonstrate a red u ction in m ortal- d om ized clinical trial of steroid ad m inistration in late
ity or ventilator d ays w ith APRV com p ared w ith op tim al ARDS, there w ere 24 p atients enrolled in the stu d y; 16 w ere
lu ng p rotective conventional ventilation has not yet been treated w ith m ethylpred nisolone and eight w ere rand om -
perform ed . ized to p lacebo (110). Fou r of the eight control patients
crossed over to the steroid arm for failu re to imp rove. The
d ose ad m inistered w as 2 m g/ kg/ d ay in d ivid ed d oses,
■ Prone positioning starting 7 d ays after the d iagnosis of ARDS and continu ing
Patient p ositioning can have a som etim es d ram atic effect for 32 d ays total. There w ere significant red u ctions in lung
on oxygenation and ventilation in severe ARDS. Changing inju ry and organ failu re scores and an im p rovem ent in the
patient p osition to p rone or steep lateral d ecubitu s p osi- Pa O 2/ FIO 2 ratio. H osp ital associated m ortality w as 12% for
tions can im p rove the d istribu tion of p erfu sion to venti- the treatm ent grou p and 62% for the control grou p; how -
lated lu ng regions lead ing to im provem ent in oxygenation ever, only fou r p atients rem ained in the p lacebo group
(107,108). Prone p ositioning in ARDS patients can im p rove becau se of p atient crossover d u ring the stu d y.
oxygenation in 60% to 70% of patients (109). A mu lticenter Within the m u lticenter trial from the ARDS Clinical
rand om ized trial of conventional treatm ent versu s p lacing Trials N etw ork, a su b-trial rand om ized p atients w ith
patients in a p rone position for 6 or m ore hours d aily for ARDS of at least 7 d ays d u ration to receive either m ethyl-
10 d ays w as cond ucted on patients w ith ALI or ARDS p red nisolone or p lacebo in a d ou ble-blind m anner (111).
(109). The m ortality rate d id not d iffer for the prone versu s Methylprednisolone therapy w as associated w ith increased
conventional positioning group at any point d uring the ventilator-free and shock-free d ays, im p roved oxygena-
stu d y, w ith u p to 6 m onths follow -up. The m ean increase in tion, and imp roved p u lm onary com p liance d u ring the first
the Pa O 2 to FIO 2 ratio w as greater in the p rone than su p ine 28 d ays. H ow ever, com p ared w ith p lacebo, m ethylpred -
grou p (63 67 vs. 45 68). There w as no d ifference nisolone w as associated w ith no d ifference in overall m or-
betw een the tw o grou ps in the incid ence of com p lications tality and a significant increase in 60- and 180-d ay
related to p ositioning. The m ean Pa O 2 of 85 to 88 m m H g m ortality rates for p atients enrolled at least 14 d ays after
and m ean Pa O 2/ FIO 2 ratio of 125 to 129 are still qu ite high the onset of ARDS. These resu lts d o not su p p ort the rou tine
for p atients w ith severe ARDS, and therefore these p atients u se of m ethylp red nisolone for p ersistent ARDS.
m ight not have been likely to benefit consid erably by the
p rone intervention in term s of m ortality.
Prone p ositioning is labor-intensive and com p licated .
■ Extracorporeal life support
The m ain risks are extubation and pressure sores. H ow - In patients w ho have acute and severe resp iratory failure
ever, a trained and d ed icated nu rsing staff that is aw are of w ho are failing all ad vanced m od es of m echanical ventila-
p otential benefits in critically ill patients w ith severe pul- tion the u se of ECLS is an op tion. The techniqu e of ECLS
m onary failu re can safely p erform the techniqu e. Prone for p atients w ith severe ARDS involves a veno-venou s or
p ositioning is a cru cial rescue tool for keeping patients veno-arterial life supp ort circu it w ith an oxygenator to
w ith severe resp iratory failure off ECLS and for lung tem porarily take over the fu nction of the lung to p rovid e
recru itm ent in p atients on ECLS. Prone positioning is not oxygenation and ventilation. While on ECLS, m echanical
u sed until Pa O 2 and Pa O 2/ FIO 2 ratio are significantly below ventilator settings are ad justed to m inim ize ventilator-
100. The techniqu e involves alternating p rone w ith su p ine ind u ced lu ng inju ry and to m axim ize the recru itm ent
positioning every 6 hours u sing approp riate cushioning of of FRC.
the d ep end ent p ortions of the bod y. Patients w ill often Use of ECLS for severe ARDS in neonates is of p roven
experience an initial w orsening in respiratory status w ith benefit (112,113), bu t for ad u lt p atients the techniqu e
each change in p osition, but this passes quickly in the first rem ains controversial. Althou gh ECLS has failed to d em on-
15 to 30 m inu tes to eventual imp rovem ent in oxygenation strate a conclusive su rvival ad vantage for ad u lts in p revi-
and ventilation, w ith 70% of the overall im p rovem ent ous prospective rand omized clinical trials, consid erable
Table 1 9 .7 O u tcom e in acu te respiratory distress Table 1 9 .8 Algor it h m for t r ea t m en t of sever e

syn drom e (ARD S) with extracorporeal a cu t e r esp ira t or y d ist r ess
life su pport (ECLS) in a d u lt s syn d r om e (ARD S)
Severe ARDS Survival Mechanical ventilator

Pressure control mode
Author Year Conventional Rx (%) ECLS Rx (%)
Limit PIP to 30–35 cm H20
Zapol 1979 8 10 Best PEEP
Gattinoni 1986 — 49 Titrate FiO2 for SaO2 90 and SvO2 70
Inverse I:E ratio
Brunet 1993 — 50
Monitors
Morris 1994 42 33 Continuous cardiac output Swan-Ganz catheter
Macha 1996 — 39 Arterial line
Kolla 1997 — 54 Treatments
Peek 1997 — 66 Prone positioning
Transfuse to Hct 35–40
Lewandowski 1997 — 55 Diuresis to dry weight (Furosemide drip or CVVH)
Ullrich 1999 — 62 Chemical sedation and paralysis
Full nutrition
Hemmila 2004 — 52
ELSO Registry 2004 — 53
Modified from Bartlett RH. Extracorporeal life support in the management of severe of blood . Anticoagu lation is necessary and is titrated as
respiratory failure. Clin Chest Med 2000;21:555–561, with permission. m easu red by w hole blood activated clotting tim e. ECLS
allow s for a d ecreasing of m echanical ventilator settings to
d ata sup port its ability to salvage severe ARDS patients nond am aging “rest” levels w hile m aintaining FRC recru it-
failing all other m eans of respiratory su pport (Table 19.7). m ent m easu res. Once native lu ng fu nction has im proved ,
The recently conclu d ed CESAR trial (Conventional ventila- the patient is trialed off of ECLS at m od erate ventilator set-
tion or ECMO for severe ad u lt resp iratory failu re) d em on- tings that allow for p otential increases in therapy—for
strated a su rvival/ absence of severe d isability benefit at 6 exam p le, FIO 2 0.5 to 0.6. If the trial off of ECLS is su ccessful,
months in favor of the ECLS group. Data pu blished in the cannu las are rem oved and recovery continues.
Lancet from the ad u lt CESAR trial show ed su rvival w ithou t In a series of 255 ad u lt p atients w ho w ere placed on
d isability at 6 m onths w as 47% in the conventional ECLS for severe ARDS refractory to all other treatm ent,
mechanical ventilation grou p and 63% in the ECLS grou p 67% w ere w eaned off ECLS and 52% su rvived to hospital
(Od d s Ratio 0.69, 95% CI 0.05–0.97, p 0.03) (114). d ischarge (117). Mu ltivariate analysis id entified the follow -
The University of Michigan experience w ith ECLS has ing p re-ECLS variables as significant ind ep end ent p red ic-
yield ed su rvival to hospital d ischarge rates of 85% in tors of su rvival: (a) age, (b) gend er, (c) arterial blood pH
neonates, 74% in child ren, and 52% in ad ults w ith severe 7.10, (d ) Pa O 2/ FiO 2 ratio, and (e) d ays of m echanical ven-
ARDS (115). The treatm ent p rogram for ad ults involves an tilation. N one of the p atients w ho su rvived requ ired
algorithm that aims to normalize bod y physiology, aggres- p erm anent m echanical ventilation or su p p lem ental oxygen
sively recru it FRC, and minimize barotraum a (Table 19.8). therap y. Patients w ho can be su ccessfu lly d ecannu lated
This algorithm used in 141 patients w ith respiratory failure from ECLS have a 77% chance of being d ischarged from the
referred for consid eration of ECLS yield ed a survival rate of hosp ital alive and going on to com p lete recovery.
62% in patients w ith severe ARDS (med ian initial Pa O 2/ FIO 2
ratio of 66) (116). Referral to an ECLS center should occur
early if there is a su spected need for this technology. This Table 1 9 .9 Ad u lt ext ra cor p or ea l life su p p or t
w ill allow safe transport of the patient and avoid ance of the (ECLS) cr it er ia
“crash on” w ith all of its inherent comp lications.
The p rim ary circu m stance for u se of ECLS in p atients Indications Contraindications
w ith severe resp iratory failu re is w hen, after op tim al • Duration of ventilation • Prolonged conventional
ventilator and m ed ical m anagem ent, the risk of d ying • 5–7 days, 7–10 days only mechanical ventilation
from ARDS is consid ered to be 80% (Table 19.9). This if ventilated with high • Poor neurologic status
requ irem ent translates to an alveoli-arterial oxygen grad i- pressures for 7 days • Incurable disease
• Compliance • Age 70 years
ent 600 m m H g or a Pa O 2/ FIO 2 ratio of 70 on 100% oxy-
• 0.5 mL/cm H2O/kg • Pulmonary artery pressures 2/3
gen. Patients shou ld also have a transpu lm onary shu nt
• Oxygenation systemic blood pressure
fraction 30% d espite m axim al conventional therap y. • PaO2/FiO2 100 • Unresolved surgical issues
Ad ult patients are typically cannu lated percutaneou sly • Shunt 30%
w ith large 21 to 23 Fr catheters for d rainage and infu sion
■ REFERENCES 28. Cou ser RJ, Ferrara TB, Fald e B, et al. Effectiveness of d exam ethasone
in preventing extu bation failure in preterm infants at increased risk
1. Kroenke K, Law rence VA, Therou x JF, et al. Op erative risk in p atients for airw ay ed em a. J Pediatr 1992;121:591–596.
w ith severe obstru ctive p u lm onary d isease. Arch Intern Med 1992;152: 29. Anene O, Meert KL, Uy H , et al. Dexam ethasone for the p revention of
967–971. p ostextubation airw ay obstru ction: a p rosp ective, rand om ized , d ou -
2. Ped ersen T, Eliasen K, H enriksen E. A p rosp ective stu d y of risk factors ble-blind , p lacebo-controlled trial. Crit Care Med 1996;24:1666–1669.
and card iop u lm onary com p lications associated w ith anaesthesia and 30. Pryor JP, Schw ab CW, Peitzm an AB. Thoracic inju ry. In: Peitzm an AB,
surgery: risk ind icators of card iop u lm onary m orbid ity. Acta Anaesthe- Rhod es M, Schw ab CW, et al, ed s. The trauma manual, 2nd ed .
siol Scand 1990;34:144–155. Philad elp hia: Lip p incott William s & Wilkins; 2002:203–223.
3. Gracey DR, Divertie MB, Did ier EP. Preoperative p u lm onary p rep ara- 31. Airw ay m anagem ent and sm oke inhalation inju ry. In: Advanced burn
tion of patients w ith chronic obstru ctive pu lm onary d isease: a life support course: provider’s manual. 2003:25–31.
prospective stu d y. Chest 1979;76:123–129. 32. Mlcak RP, Su m an OE, H ernd on DN . Resp iratory m anagem ent of
4. Sm etana GW. Preop erative p u lm onary evalu ation. N Engl J Med 1999; inhalational inju ry. Burns 2007;33:2–13.
340:937–944. 33. Ryan CM, Schoenfeld DA, Thorp e WP, et al. Objective estim ates of the
5. Johnson RG, Arozu llah AM, N eu m ayer L, et al. Mu ltivariable pred ic- probability of d eath from bu rn inju ries. N Engl J Med 1998;338:
tors of postoperative respiratory failure after general and vascular 362–366.
surgery: resu lts from the p atient safety in su rgery stu d y. J Am Coll 34. H ap onik EF, Crapo RO, H ernd on DN , et al. Sm oke inhalation. Am Rev
Surg 2007;204:1188–1198. Respir Dis 1988;138:1060–1063.
6. Sm etana GW. Evalu ation of p reop erative p u lm onary risk. Up ToDate 35. Weiss SM, Lakshim inarayan S. Acu te inhalation inju ry. Clin Chest Med
17.1. Available at: http :/ / w w w.u td ol.com . Accessed May 20, 2009. 1994;15:103–116.
7. Wightm an JA. A p rosp ective su rvey of the incid ence of p ostop erative 36. H eim bach DM, Waeckerle JF. Inhalation inju ries. Ann Emerg Med
pu lm onary com plications. Br J Surg 1968;55:85–91. 1988;17:1316–1320.
8. Morton H JV. Tobacco sm oking and p u lm onary com p lications after 37. Dem ling R. Sm oke inhalation inju ry. New Horiz 1993;1:422–484.
surgery. Lancet 1944;1:368–370. 38. Mand el J, H ales CA. Sm oke inhalation. Up ToDate 17.1. Available at:
9. Brooks-Bru nn JA. Pred ictors of p ostop erative p u lm onary com plica- http :/ / w w w.u td ol.com . Accessed May 22, 2009.
tions follow ing abd om inal su rgery. Chest 1997;111:564–571. 39. Seger D, Welch L. Carbon m onoxid e controversies: N eu rop sychologic
10. Warner MA, Offord KP, Warner ME, et al. Role of p reop erative cessa- testing, m echanism s of toxicity, and hyp erbaric oxygen. Ann Emerg
tion of sm oking and other factors in p ostop erative p u lm onary com - Med 1994;24:242–248.
plications: a blind ed p rosp ective stu d y of coronary artery bypass 40. Dem ling RH . Sm oke inhalation inju ry. In: Shoem aker WC, Ayres SM,
patients. Mayo Clin Proc 1989;64:609–616. Genvik A, et al, ed s. Textbook of critical care, 3rd ed . Philad elp hia: W.B.
11. Gold m an L, Cald era DL, N u ssbau m SR, et al. Mu ltifactorial ind ex of Saund ers Com p any; 1995:1506–1516.
card iac risk in noncard iac su rgical p roced u res. N Engl J Med 1977; 41. H erlihy JP, Verm eu len PM, Josep h PM, et al. Im p aired alveolar
297:845–850. m acrophage function in sm oke inhalation inju ry. J Cell Physiol 1995;
12. Law rence VA, Dhand a R, H ilsenbeck SG, et al. Risk of p ulm onary 163:1–8.
com p lications after elective abd om in al su rgery. Chest 1996;110: 42. Desai MH , Mlcak R, Richard son J, et al. Red u ction in m ortality in
744–750. ped iatric patients w ith aerosolized heparin/ N -acetylcysteine therapy.
13. Gerson MC, H u rst JM, H ertzberg VS, et al. Pred iction of card iac and J Burn Care Rehabil 1998;19:210–212.
pu lm onary com p lications related to elective abd om inal and noncar- 43. Bartlett JG. Asp iration p neu m onia. Up ToDate 17.1. Available at:
d iac thoracic surgery in geriatric p atients. Am J Med 1990;88:101–107. http :/ / w w w.u td ol.com . Accessed May 26, 2009.
14. Wong D, Weber EC, Schell MJ, et al. Factors associated w ith p ostop er- 44. Greenfield LJ, Singleton RP, McCaffree DR, et al. Pu lm onary effects of
ative p u lm onary com p lications in p atients w ith severe chronic exp erim ental grad ed asp iration of hyd rochloric acid . Ann Surg 1969;
obstructive pu lm onary d isease. Anesth Analg 1995;80:276–284. 170:74–86.
15. Warner DO, Warner MA, Barnes RD, et al. Perioperative respiratory 45. Fisk RL, Sym es JF, Ald rige LL, et al. The p athop hysiology and exp eri-
complications in patients with asthma. Anesthesiology 1996;85:460–467. m ental therap y of acid p neu m onitis in ex vivo lu ngs. Chest 1970;57:
16. Arozullah AM, Daley J, H end erson WG, et al. Mu ltifactorial risk 364–370.
ind ex for pred icting postoperative respiratory failu re in m en after 46. Cam eron JL, Cald ini P, Tou ng JK, et al. Aspiration pneum onia: physio-
m ajor noncard iac su rgery. Ann Surg 2000;232:242–253. logic data follow ing exp erim ental asp iration. Surgery 1973;72:238–245.
17. Kroenke K, Law rence VA, Therou x JF, et al. Postop erative com p lica- 47. Bynu m LJ, Pierce AK. Pu lm onary asp iration of gastric contents. Am
tions after thoracic and m ajor abd om inal su rgery in p atients w ith and Rev Respir Dis 1976;114:1129–1136.
w ithout obstru ctive lu ng d isease. Chest 1993;104:1445–1451. 48. Broe PJ, Toung TJ, Perm u tt S, et al. Asp iration p neu m onia: treatm ent
18. Milled ge JS, N u nn JF. Criteria of fitness for anaesthesia in p atients w ith p ulm onary vasod ilators. Surgery 1983;94:95–99.
w ith chronic obstru ctive lu ng d isease. Br Med J 1975;3:670–673. 49. Cam eron JL, Sebor J, And erson PR, et al. Asp iration p neu m onia:
19. Thom as DR, Ritchie CS. Preop erative assessm ent of old er ad u lts. J Am results of treatm ent by p ositive-p ressu re ventilation in d ogs. J Surg
Geriatr Soc 1995;43:811–821. Res 1968;8:447–457.
20. Pasu lka PS, Bistian BR, Benotti PN , et al. The risks of su rgery in obese 50. Peitzm an AB, Shires GT III, Illner H K, et al. Pu lm onary acid inju ry:
patients. Ann Intern Med 1986;104:540–546. effects of p ositive end -exp iratory p ressu re and crystalloid vs. colloid
21. H all JC, Tarala MD, H all JL, et al. A m u ltivariate analysis of the risk of fluid resu scitation. Arch Surg 1982;117:662–668.
pu lm onary com plications after lap arotom y. Chest 1991;99:923–927. 51. Toung TJ, Cam eron JL, Kim era T, et al. Asp iration p neu m onia: treat-
22. Morino M, Top pino M, Forestieri P, et al. Mortality after bariatric sur- m ent w ith osm otically active agents. Surgery 1981;89:588–593.
gery: analysis of 13871 m orbid ly obese patients from a national reg- 52. Wolfe JE, Bone RC, Ru th WE. Effects of corticosteroid s in the treat-
istry. Ann Surg 2007;246:1002–1009. m ent of patients w ith gastric asp iration. Am J Med 1977;63:719–722.
23. Merkow RP, Bilim oria KY, McCarter MD, et al. Effect of bod y m ass 53. Bartlett JG. Anaerobic bacterial infections of the lu ng and p leu ral
ind ex on short-term ou tcom es after colectom y for cancer. J Am Coll sp ace. Clin Infect Dis 1993;4:S248–S255.
Surg 2009;208:53–61. 54. Finegold SM. Aspiration p neu m onia. Rev Infect Dis 1991;13(Su p p l 9):
24. Qaseem A, Snow V, Fitterm an N , et al. Risk assessment for and strate- S737–S742.
gies to red uce periop erative p ulm onary com plications for patients 55. Bartlett JG. Anaerobic bacterial p neu m onitis. Am Rev Respir Dis 1979;
und ergoing noncard iothoracic su rgery: a gu id eline from the Am erican 119:19–23.
College of Physicians. Ann Intern Med 2006;144:575–580. 56. Gilbert DN , Moellering RC Jr, Eliop ou los GM, et al, ed s. The Sanford
25. Bartlett RH , Rich PB. Pu lm onary insufficiency. In: Wilm ore DW, guide to antimicrobial therapy, 38th ed . Sp erryville, VA: Antim icrobial
Cheung LY, H arken AH , et al, ed s. ACS Surgery: principles and practice, Therapy, Inc.; 2008.
2003 ed . N ew York, N Y: WebMD Inc; 2003:1047–1057. 57. Wang JL, Chen KY, Fang CT, et al. Changing bacteriology of ad u lt
26. Zibrak JD. Preoperative p u lm onary fu nction testing. Am erican Col- com m unity-acqu ired lu ng abscess in Taiw an: Klebsiella pneumoniae
lege of Physicians. Ann Intern Med 1990;112:793–794. versu s anaerobes. CID 2005;40:915–925.
27. N ew som e H H Jr. Com p lications of thyroid su rgery. In: Greenfield LG, 58. Torres A, Serra-Batlles J, Ros E, et al. Pu lm onary asp iration of gastric
ed . Complications in surgery and trauma, 2nd ed . Philad elphia, PA: J.B. contents in patients receiving m echanical ventilation: the effect of
Lip pincott Com p any; 1990:649–659. bod y p osition. Ann Intern Med 1992;116:540–543.
59. Orozco-Levi M, Torres A, Ferrer M, et al. Sem irecu m bent p osition p ro- the em piric treatm ent of suspected ventilator-associated pneum onia.
tects from p ulm onary aspiration but not com pletely from gastroe- Crit Care Med 2008;36:737–744.
sop hageal reflux in m echanically ventilated p atients. Am J Respir Crit 84. H em m ila MR, H irschl RB. Ad vances in ventilatory su p p ort of the
Care Med 1995;152:1387–1390. ped iatric su rgical patient. Curr Opin Pediatr 1999;11:241–248.
60. Drakulovic M, Torres A, Bau er TT, et al. Su p ine bod y p osition as a risk 85. Bernard GR, Artigas A, Brigham KL, et al. The Consensu s Com m ittee
factor for nosocom ial pneum onia in m echanically ventilated patients: Rep ort of the Am erican-Eu rop ean Consensu s Conference on ARDS:
a rand om ized trial. Lancet 1999;354:1851–1858. d efinitions, m echanism s, relevant ou tcom es and clinical trial coord i-
61. Zavala DC, Rhod es ML. Foreign bod y rem oval: a new role for the nation. Intensive Care Med 1994;20:225–232.
fiberop tic bronchoscop e. Ann Otol Rhinol Laryngol 1975;84:650–656. 86. Brow er RG, Morris A, Schoenfeld D, et al. The Acu te Resp iratory Dis-
62. Am erican Thoracic Society, Infectiou s Diseases Society of Am erica. tress Synd rom e N etw ork. Ventilation w ith low er tid al volu m es as
Gu id elines for the m anagem ent of ad u lts w ith hosp ital-acqu ired , ven- com pared w ith trad itional tid al volum es for acu te lung injury and
tilator-associated , and healthcare-associated p neu m onia. Am J Respir the acu te respiratory d istress synd rom e. N Engl J Med 2000;342:
Crit Care Med 2005;171:388–416. 1301–1308.
63. Cu nnion KM, Weber DJ, Broad head WE, et al. Risk factors for nosoco- 87. Beau fils F, Mercier JC, Farnou x C, et al. Acu te resp iratory d istress syn-
m ial pneum onia: com p aring ad u lt critical-care p op u lations. Am J d rom e in child ren. Curr Opin Pediatr 1997;9:207–212.
Respir Crit Care Med 1996;153:158–162. 88. Bu lger EM, Jurkovich GJ, Gentilello LM, et al. Cu rrent clinical op tions
64. N ational N osocom ial Infections Su rveillance (N N IS) rep ort, d ata for the treatm ent and m anagem ent of acu te resp iratory d istress syn-
su m m ary from October 1986-Ap ril 1997, issu ed May 1997. A rep ort d rom e. J Trauma 2000;48: 562–572.
from the N N IS System . Am J Infect Control 1997;25:477–487. 89. Dem ling RH . Pu lm onary d ysfu nction. In: Wilm ore DW, Cheu ng LY,
65. Tablan OC, And erson LJ, Ard en N H , et al. Gu id eline for p revention of H arken AH , et al, ed s. ACS Surgery principles and practice 2003. N ew
nosocom ial p neu m onia. Centers for Disease Control and Prevention. York, N Y: WebMD Inc; 2003:1433–1453.
Respir Care 1994;39:1191–1198. 90. H ansen-Flaschen J, Siegel MD. Acu te resp iratory d istress synd rom e:
66. File TM Jr. Risk factors and p revention of hosp ital-acqu ired , ventila- d efinition; ep id em iology; d iagnosis; and etiology. Up ToDate 17.1.
tor-associated , and healthcare-associated p neu m onia in ad u lts. Up To- Available at: http :/ / w w w.u td ol.com . Accessed May 27, 2009.
Date 17.1. Available at: http :/ / w w w.u td ol.com . Accessed May 27, 91. Webb H H , Tierney DF. Exp erim ental p u lm onary ed em a d u e to inter-
2009. m ittent positive pressure ventilation w ith high inflation pressures.
67. Prod ’hom G, Leuenberger P, Koerfer J, et al. N osocom ial p neu m onia Protection by p ositive end -exp iratory p ressu re. Am Rev of Resp Dis
in m echanically ventilated p atients receiving antacid , ranitid ine, or 1974;110:556–565.
su cralfate. Ann Intern Med 1994;120:653–662. 92. Dreyfu ss D, Basset G, Soler P, et al. Interm ittent p ositive-p ressu re
68. Schw eickert WD, Gehlbach BK, Pohlm an AS, et al. Daily interru ption hyperventilation w ith high inflation pressures p rod u ces p ulm onary
of sed ative infusions and com plications of critical illness in m echani- m icrovascu lar inju ry in rats. Am Rev of Resp Dis 1985;132:880–884.
cally ventilated p atients. Crit Care Med 2004;32:1272–1276. 93. Tsu no K, Prato P, Kolobow T. Acu te lu ng inju ry from m echanical ven-
69. Milbrand t EB, Kersten A, Kong L, et al. H alop erid ol u se is associated tilation at m od erately high airw ay p ressu res. J Appl Physiol 1990;69:
w ith low er hospital m ortality in m echanically ventilated p atients. Crit 956–961.
Care Med 2005;33:226–229. 94. Ranieri VM, Su ter PM, Tortorella C, et al. Effect of m echanical ventila-
70. File TM Jr. Ep id em iology, p athogenesis, and m icrobiology of hosp ital- tion on inflam m atory m ed iators in patients w ith acute respiratory d is-
acqu ired , ventilator-associated , and healthcare-associated p neum onia tress synd rom e: a rand om ized , controlled trial. JAMA 1999;282;54–61.
in ad u lts. UpToDate 17.1. Available at: http :/ / w w w.u td ol.com . 95. Kolobow T, Moretti MP, Fum agalli R, et al. Severe im p airm ent in lu ng
Accessed May 27, 2009. function ind uced by high peak airw ay pressu re d u ring m echanical
71. Wahl WL, Franklin GA, Brand t MM, et al. Does bronchoalveolar ventilation. An exp erim ental stu d y. Am Rev Respir Dis 1987;135:
lavage enhance ou r ability to treat ventilator-associated pneum onia in 312–315.
a trau m a-bu rn intensive care u nit? J Trauma 2003;54:633–639. 96. Savel RH , Yao EC, Grop per MA. Protective effects of low tid al volu m e
72. Fagon JY, Chastre J, Wolff M, et al. Invasive and noninvasive strategies ventilation in a rabbit m od el of Pseudomonas aeruginosa-ind uced acu te
for m anagem ent of su sp ected ventilator-associated p neu m onia. A lung inju ry. Crit Care Med 2001;29:392–398.
rand om ized trial. Ann Intern Med 2000;132:621–630. 97. Parsons PE, Eisner MD, Thom p son BT, et al. Low er tid al volu m e ven-
73. Croce MA, Fabian TC, Schu rr MJ, et al. Using bronchoalveolar lavage tilation and plasm a cytokine m arkers of inflam m ation in patients
to d istinguish nosocom ial pneum onia from system ic inflam m atory w ith acute lu ng injury. Crit Care Med 2005;33:1–6.
resp onse synd rom e: a p rosp ective analysis. J Trauma 1995;39:1134– 98. H ickling KG, H end erson SJ, Jackson R. Low m ortality associated w ith
1140. low volum e pressure lim ited ventilation w ith perm issive hypercapnia
74. Croce MA, Fabian TC, Wad d e-Sm ith L, et al. Utility of Gram ’s stain in severe ad ult resp iratory d istress synd rom e. Intensive Care Med
and efficacy of qu antitative cu ltu re for p osttrau m atic p neum onia. 1990;16:372–377.
Ann Surg 1998;227:743–751. 99. H ickling KG, Walsh J, H end erson S, et al. Low m ortality rate in ad u lt
75. Minei JP, N athens AB, West M, et al. Gu id elines for p revention, d iag- respiratory d istress synd rom e u sing low -volu m e, p ressu re-lim ited
nosis, and treatm ent of ventilator-associated p neu m onia (VAP) in the ventilation w ith perm issive hyp ercap nia: a p rosp ective stu d y. Crit
trau m a patient. J Trauma 2006;60:1106–1113. Care Med 1994;22:1568–1578.
76. Med u ri GU, Johanson WG Jr. International consensu s conference: 100. Kregenow DA, Ru benfeld GD, H u d son LD, et al. H yp ercap nic acid o-
clinical investigation of ventilator-associated p neu m onia. Introd u c- sis and m ortality in acu te lung inju ry. Crit Care Med 2006;34:229–231.
tion. Chest 1992;102:551S–552S. 101. Artigas A, Bernard GR, Carlet J, et al. The Am erican-Eu rop ean Con-
77. Kollef MH , Sherm an G, Ward S, et al. Inad equ ate antim icrobial treat- sensu s Conference on ARDS, p art 2: ventilatory, p harm acologic, su p -
m ent of infections: a risk factor for hospital m ortality am ong critically portive therapy, stu d y d esign strategies and issu es related to recovery
ill patients. Chest 1999;115:462–474. and rem od eling. Intensive Care Med 1998;24:378–398.
78. Rello J, Gallego M, Mariscal D, et al. The valu e of rou tine m icrobial 102. Am ato MB, Barbas CS, Med ieros DM, et al. Beneficial effects of the
investigation in ventilator-associated p neu m onia. Am J Respir Crit “op en lu ng app roach” w ith low d istend ing p ressu res in acu te respira-
Care Med 1997;156:196–200. tory d istress synd rom e: a prospective rand om ized stu d y on m echani-
79. Rello J, Diaz E. Pneum onia in the intensive care u nit. Crit Care Med cal ventilation. Am J Respir Crit Care Med 1995;152:1835–1846.
2003;31:2544–2551. 103. Am ato MB, Barbas CS, Med ieros DM, et al. Effect of a p rotective-ven-
80. Galil K, Zaleznik DF. N osocom ial p neu m onia. Up ToDate 11.3. Avail- tilation strategy on m ortality in the acute respiratory d istress syn-
able at: http:/ / w w w.u td ol.com . Accessed Febru ary 17, 2003. d rom e. N Engl J Med 1998;338:347–354.
81. H ilf M, Yu VL, Sharp J, et al. Antibiotic therap y for p seu d om onas 104. H ager DN , Krishnan JA, H ayd en DL, et al. Tid al volu m e red u ction in
aeru ginosa bacterem ia: ou tcom e correlations in a p rosp ective stud y of patients w ith acu te lu ng inju ry w hen plateau pressures are not high.
200 p atients. Am J Med 1989;87:540–546. Am J Respir Crit Care Med 2005;172:1241–1245.
82. Chastre J, Wolff M, Fagon JY. Com p arison of 8 vs 15 d ays of antibiotic 105. Mercat A, Richard JM, Vielle B, et al. Positive end -exp iratory p ressu re
therapy for ventilator-associated pneum onia in ad ults: a rand om ized setting in ad ults w ith acu te lu ng inju ry and acu te resp iratory d istress
trial. JAMA 2003;290:2588–2598. synd rom e. JAMA 2008;299:646–655.
83. H eyland DK, Dod ek P, Mu sced ere J, et al. Canad ian Critical Care Tri- 106. Mead e MO, Cook DJ, Guyatt GH , et al. Ventilation strategy u sing
als Group . Rand om ized trial of com bination versu s m onotherap y for low tid al volum es, recruitm ent m aneu vers, and high p ositive end -
expiratory pressure for acute lu ng injury and acute respiratory d is- 113. UK Collaborative ECMO Trial Grou p . UK collaborative rand om ized
tress synd rom e. JAMA 2008;299:637–645. trial of neonatal extracorp oreal m em brane oxygenation. Lancet 1996;
107. Piehl MA, Brow n RS. Use of extrem e p osition changes in acu te resp i- 348:75–82.
ratory failu re. Crit Care Med 1976;4:13–14. 114. Peek GJ, Mu gford M, Tiru voip ati R, Wilson A, Allen E, Thalanany
108. Dou glas WW, Rehd er K, Beynen FM, et al. Im p roved oxygenation in MM, H ibbert CL, Tru esd ale A, Clem ens F Coop er N , Firm in RK,
p atients w ith acu te resp iratory failu re: the p rone p osition. Am Rev Elbou rne D; CESAR trial collaboration. Efficacy and econom ic
Respir Dis 1977;115:559–566. assessm ent of conventional ventilatory su pp ort versu s extracorp o-
109. Gattinoni L, Tognoni G, Pesenti A, et al. Effect of p rone p ositioning on real m em brane oxygenation for severe ad u lt resp iratory failu re
the survival of p atients w ith acu te resp iratory failu re. N Engl J Med (CESAR): a m u lticentre rand om ised controlled trial. Lancet 2009;374:
2001;345:568–573. 1351–1363.
110. Med u ri GU, H ead ley AS, Gold en E, et al. Effect of p rolonged m ethyl- 115. Extracorp oreal Life Sup p ort Organization. Annual ECMO Registry
p red nisolone therap y in u nresolving acu te resp iratory d istress syn- Report. 2003.
d rom e. JAMA 1998;280:159–165. 116. Rich PB, Aw ad SS, Kolla S, et al. An ap p roach to the treatm ent of
111. Steinberg KP, Hu d son LD, Good m an RB. National Heart, Lung, and severe ad u lt respiratory failu re. J Crit Care 1998;13:26–36.
Blood Institu te Acu te Respiratory Distress Synd rom e (ARDS) Clinical 117. H em m ila MR, Row e SA, Bou les TN , et al. Extracorp oreal life su p p ort
Trials N etw ork. Efficacy and safety of corticosteroid s for p ersistent for severe acu te resp iratory d istress synd rom e in ad u lts. Ann Surg
acute respiratory d istress syndrom e. N Engl J Med 2006;354:1671–1684. 2004;240:595–607.
112. Bartlett RH , Roloff DW, Cornell RG, et al. Extracorp oreal circulation
in neonatal resp iratory failu re: a p rosp ective rand om ized stu d y. Pedi-
atrics 1985;76:479–487.
CHAPTER
20
Abnormalities in Coagulation
Alvin H. Schmaier
■ INTRODUCTION more throm bin activation throu gh factors IXa and VIIIa
and , su bsequ ently, factors Xa and Va (Fig. 20.1). Inhibitors
Bleed ing or throm bosis is a seriou s com p lication associated to each of the coagu lation and fibrinolysis enzym es ad d i-
w ith elective or em ergent surgery. When ap proaching the tionally regu late this system. Und er p hysiologic circu m-
p roposed su rgical p atient, a few critical item s shou ld be stances, factor XIIa is not an activator of factor XI to initiate
obtained to exclu d e the p ossibility of abnorm al bleed ing coagu lation reactions to p revent bleed ing. In d isease or
and increased risk for throm bosis arising ind ep end ent of inju ry su ch as that seen after p latelet throm bu s, sepsis,
com plications d u ring the proced u re. This chapter aim s trau m a, and card iop u lm onary byp ass (CPB), factor XIIa
(a) to p rovid e a concise and thorou gh ap p roach to assess- form s by au toactivation on p olysom es, ribonu cleic acid
ing bleed ing risk in the p rosp ective su rgical p atient; (b) to (RN A), aggregated p rotein, and exp osed collagen to acti-
p rovid e a practical and thorou gh d ifferential d iagnosis of vate factor XI, increasing throm bin formation as w ell (Fig.
cau ses of su rgical bleed ing and throm bosis; and (c) to su g- 20.1). In these circu m stances factor XII contribu tes to the
gest general and sp ecific m eans to m anage variou s bleed - extent of throm bus form ation in injured vessels and
ing states and p revent p ostop erative throm bosis in su rgical intravascu lar coagu lation (4–6).
p atients. Although there is a present-day elegant und erstanding
of physiologic hemostasis, the clinician need s to make man-
■ ASSESSING RISK FOR BLEEDING IN agement decisions based upon clinical tests. The current
PROSPECTIVE SURGICAL PATIENTS means to d iagnosis of a bleed ing risk in the prospective sur-
gery patient is still by history and simple laboratory tests
Bleed ing or throm bosis is the ill consequ ence of a loss in (Table 20.1) (7). Prospectively, thrombosis risk in a patient
the d elicate balance betw een hem ostasis (clot form ation), cannot be assessed by any laboratory testing; it requires
fibrinolysis (clot lysis), and anticoagu lation (regu lation) of assessment of the patient’s past medical history, ambulatory
the various p lasm a proteins and cells in the intravascu lar ability, and the nature of the proposed surgery. The physician
com partment. For 40 years, the blood coagulation system should ask if there have been prior surgeries, injuries, or
has been rep resented as a cascad e of p roteolytic reactions tooth extractions, and, if so, whether there has been abnormal
lead ing to clot form ation (1). This concep t really d escribes bleeding requiring additional care, transfusions, or revisits to
blood coagu lation that occurs in a test tube and not physio- the physician or hospital, for either the patient or an immedi-
logic hem ostasis. A cu rrent hypothesis is that the blood ate family member. Similarly, these questions should be
coagulation, fibrinolysis, and anticoagu lant system s are an asked concerning any bleeding history of an immediate fam-
interacting grou p of p roteins that am p lify the activation ily member. Furthermore, the surgeon needs to take a thor-
and inhibition of each other (Fig. 20.1) (2,3). In physiologic ough medication history. The common use of aspirin and
hem ostasis, the initiating event is factor VIIa-tissue factor other platelet inhibitors (e.g., clopidogrel, serotonin release
(TF-VIIa) activating factor IX to factor IXa. This pathw ay inhibitor antidepressants, and vitamin E) that interfere with
occurs becau se a p rotein called tissu e factor pathw ay platelet function need s to be recorded. A positive answer to
inhibitor (TFPI) blocks the d irect p hysiologic activation of any one of these questions puts the patient into a higher
factor X by TF-VIIa (2). Factor IXa (IXa) in the p resence of bleeding risk category. Alternatively, thrombosis risk is
factor VIIIa (VIIIa) activates factor X to factor Xa (Xa) w hich assessed by prior history and the ambulatory nature of the
in the p resence of factor Va (Va) activates p rothrom bin (II) patient. As will be d iscussed below, the nature of the surgical
to throm bin (IIa) (Fig. 20.1). A little throm bin p roteolyzes proced ure contributes to the risk for thrombosis.
fibrinogen to m ake a fibrin clot. H ow ever, this sam e throm - The clinical laboratory provid es useful information to
bin also activates factor XI to factor XIa (XIa) to am plify assess bleed ing risk in a patient preparing for su rgery. There
is controversy regard ing the cost-effective approach to
Alvin H. Schmaier: Case Western Reserve University, 2103 assess bleed ing risk. The activated partial thrombop lastin
Cornell, WRB 2-130, Cleveland , OH 44106-7284 time (APTT) is the most global screening assay for a
200
Chapter 20 • Abnormalities in Coagulation 201
Initiation of Coagulation FIGURE20.1. Physiologic hemostasis. Physiologic

hemostasis is initiated by tissue factor-factor VIIa (TF-
XII VII VIIa) activating factor IX. The plasma protein tissue factor
Tissue factor pathway inhibitor (TFPI) blocks factor VIIa-TF from directly
HK
PK activating factor X. Factor IXa in the presence of factor
XI VIIIa (IXa VIIIa) activates factor X to factor Xa. Factor
XIIa VIIa Xa in the presence of factor Va (Xa Va) then activates
prothrombin to thrombin (IIa). Formed thrombin (IIa) can
Tissue factor/VIIa
clot fibrinogen to make fibrin. Thrombin also activates fac-
IX
XIa tor XIII to covalently crosslink the fibrin clot making it
PL, Ca++ insoluble. If the need to generate thrombin is great, the ini-
Ca++ tially formed thrombin will also activate factor XI to factor
XIa (XIa). Formed factor XIa then amplifies factor IX acti-
IXa X vation leading to amplified thrombin formation (IIa).
PL, Ca++
Amplification of Ca++
Coagulation VIII VIIIa
Xa
Prothrombin
PL, Ca++
Va V
Thrombin
Fibrinogen XIII
Soluble fibrin monomers Ca++
XIIIa
Polymerized fibrin clot
Covalently crosslinked fibrin clot
coagulation protein d efect, but it w ill not pick up the rare bleed ing time and the PFA-100 are not analogous. The PFA-
(1/ 500,000 to 1/ 1,000,000) patient w ith factor VII d eficiency. 100 measures platelet activation ind u ced by tw o agonists
Alternatively, the prothrombin time (PT), if abnormal, is und er high shear. It d oes not make a d iagnosis of a bleed ing
probably a better pred ictor of bleed ing at the time of su r- d isord er. Its resu lt, like that of the bleed ing time test, is only
gery than the APTT, if abnormal. The bleed ing tim e, w hich either “norm al” or “abnorm al.” In m y p ractice, w hich is
is not u sed m u ch anym ore, has been show n not to p red ict hem ostasis and throm bosis consu ltation, I u se neither the
abnormal su rgical bleed ing. H ow ever, a patient w ho has a bleed ing time nor PFA-100 w hen I suspect a bleed ing d isor-
bleed ing d isord er, but w ho is on no med ications and has a d er by history in a patient w ith a normal APTT and PT. I
norm al APTT and PT, m ay have von Willebrand d isease or prefer to obtain the specific assays for von Willebrand d is-
a platelet function d isord er. These p latelet fu nction d isor- ease and platelet fu nction d efects. Making a specific d iagno-
d ers may be d iagnosed by bleed ing time or a new er assay sis as to the bleed ing state is essential because prophylactic
that has become w id ely available, the platelet function ana- therapies for von Willebrand d isease or a platelet function
lyzer (PFA-100). Use of these latter tests requires that the d efect, respectively, are quite d ifferent. The follow ing is a
patient being stu d ied is on no interfering med ication. The d escription of w hat the tests measure. The d ecision to use
all or a p ortion of these tests for screening to d etermine risk
for bleed ing has to rest in the hand s of the clinician, based
Table 2 0 .1 Pr esu r gica l va r ia bles t o a ssess
on the history of the patient.
bleed in g a n d clot t in g r isk
The APTT and PT screening tests m easu re sp ecific p or-
History tions of the coagu lation p rotein system (Fig. 20.2, Table
Patient history of bleeding at surgery, trauma, tooth extractions 20.2). Know ing the resu lts of these assays p rovid es m ajor
Family history of bleeding at surgery, trauma, tooth extractions d iagnostic p ow er to p red ict the p otential cau se of bleed ing
Medication history: antiplatelet agents, NIADS, anticoagulants
in a p rosp ective su rgical p atient. The d ifferential d iagnosis
:
of an isolated p rolonged APTT is d ep end ent u p on w hether
Complete blood count including platelet count
Activated partial thromboplastin time the p atient has a bleed ing history or not. If there is a bleed -
Prothrombin time ing history, factor VIII (VIII) d eficiency is nine tim es more
com m on than factor IX (IX) d eficiency. Both occur alm ost
NIADS, nonsteroidal anti-inflammatory drugs. exclu sively in m ales since they are sex-linked . These
SURFACE TISSUE
ACTIVATION THROMBOPLASTIN
Table 2 0 .2 D ifferen t ia l dia gn osis of a bn or m a l
scr een in g t est s for bleedin g disorder s
INTRINSIC EXTRINSIC
Abnormal activated partial thromboplastin time (APTT) alone
Associated with bleeding: VIII, IX, XI defects
XII, PK Not associated with bleeding: XII, prekallikrein (PK), high molecular
HK
VII
weight kininogen (HK), lupus anticoagulants
XI
Abnormal prothrombin time (PT) alone
IX
VIII VII defects
Ac
Mild defects in fibrinogen, factors II, X, or Vcan sometime appear as

t
iva
slight prolongations of the PT alone, before the APTT lengthens

ted
Prothrombin Time
Partial Thromboplastin Time
COMMON
Combined abnormal APTT and PT
Medical conditions: anticoagulants, DIC, liver disease, vitamin K
X deficiency, massive transfusion
Rarely dysfibrinogenemias, factors X, V, and II defects
V
Long bleeding time or PFA-100
II Normal platelet count: von Willebrand disease or a platelet function
I defect (congenital or acquired—usually medication)
(FIBRINOGEN)
Low platelet count ( 100,000/ l); low hematocrit ( 20%) will give
Thrombin Time
an abnormal PFA-100 result
These kind s of d efects are m ost likely w ith inp atients. The
FIBRIN m ost comm on cau ses of com bined p rolonged APTT and PT
are the follow ing: anticoagu lation, d issem inated intravas-
FIGURE20.2. Description of common coagulation blood tests and what pro-
teins these tests measure. The activated partial thromboplastin time (APTT) cu lar coagu lation (DIC), liver d isease, vitam in K d eficiency,
measures the functional integrity of all of the proteins of the so-called intrinsic and massive transfu sions. Each of these entities w ill be d is-
(INTRINSIC) and common (COMMON) pathways of the coagulation system. cu ssed in m ore d etail in the next section of this chap ter.
These proteins include factor XII (XII), prekallikrein (PK), high molecular weight Once these m ed ical cond itions are exclu d ed , only rare
kininogen (HK), factors XI, IX, VIII, X, V, II (thrombin), and I (fibrinogen). The pro-
thrombin time (PT) measures the functional integrity of the proteins of the so- coagu lation p rotein d efects or d eficiencies shou ld be con-
called extrinsic (EXTRINSIC) pathway [Factor VII (VII)] and the proteins of the sid ered . The m ost com m on cau se of an abnorm al coagu la-
common pathway. The thrombin clotting time only measures the functional tion p rotein d efect giving a p rolonged PT and APTT is
integrity of fibrinogen.
an abnorm al fibrinogen (d ysfibrinogenem ia). Dysfibrino-
genem ias are m ost com m only seen in p atients w ith liver
ind ivid u als have a life-long bleed ing history. Spontaneou s d isease, from any cau se. Mu ch less com m on w ou ld be d efi-
inhibitors to VIII arise in patients w ho are eld erly, p ostp ar- ciency or inhibitors to factors X, V, and II (p rothrom bin).
tu m , have a connective tissue d isord er, or have a B cell Tru e d eficiencies of each of these three p roteins are p roba-
malignancy. Factor XI (XI) d eficiency is m u ch less com m on bly incom p atible w ith norm al fetal gestation and parturi-
and 50% of the p atients are ind ivid uals w ho are Jew ish tion. The extrem ely rare p atient w ho ap p ears to be fully
w ith an Eastern Eu rop ean background . Alternatively, if d eficient in these p roteins actu ally has a sm all am ou nt of
there is no bleed ing history, but the APTT alone is p ro- the p rotein of interest being p rod u ced . More com m only,
longed , the m ost likely cau se for the prolonged APTT w ill antibod ies to factors V that arise sp ontaneou sly or after
be a lu p u s anticoagu lant. A lu pu s anticoagulant is not a top ical throm bin u se from a p reviou s su rgery and antibod -
bleed ing risk; p arad oxically, it is a throm bosis risk. Other ies to factor II and X arising in patients w ith system ic lupu s
cau ses of long APTT that are not associated w ith bleed ing erythem atosus anticoagulants and m alignancy may be
includ e factor XII (XII), prekallikrein, or high m olecu lar seen. Acqu ired factor X d eficiency also arises in patients
w eight kininogen (H K) d eficiencies (Fig. 20.2, Table 20.2). w ith am yloid osis.
These last three p rotein d efects are qu ite rare, and m ost A bleed ing p atient w ith a normal PT, APTT, and platelet
physicians w ill never see a p atient w ith these d efects. cou nt m ay have von Willebrand d isease or, less com m only,
An isolated abnorm al PT is com m only associated w ith a a tru e p latelet fu nction d efect (ratio 9:1, von Willebrand
factor VII (VII) d eficiency. This d isord er is quite uncommon, d isease : p latelet fu nction d efect not ind u ced by m ed ica-
bu t is associated w ith abnormal bleed ing at the time of su r- tion). Patients w ith von Willebrand d isease and p latelet
gery. Depend ing up on the sensitivity of the thromboplastin fu nction d efects su ffer from easy bru isability of soft tissu es.
in the PT reagent, an isolated abnorm al PT can also occu r Specialized testing is required to make the d iagnosis of a
w ith a d ysfibrinogenemia or factor X, V, and II d eficiencies. d eficiency or d efect in the von Willebrand factor or a
When both the APTT and PT are p rolonged , the p hysi- platelet fu nction d efect. Finally, all p atients w ith a red u ction
cian need s to consid er a num ber of m ed ical cond itions. in their p latelet cou nt so that it is below 100,000/ l are at
increased risk of bleed ing at the tim e of surgery. The ■ Anticoagulation

platelet cou nt should never be overlooked in the p reop era-
tive evalu ation. Thus, all preoperative patients shou ld have Anticoagulant and antip latelet agents su ffuse m ed ical
a PT, APTT, and platelet count. If there is a strong bleed ing p ractice tod ay, allow ing for interventional p roced u res as
history and these tests are norm al, the patient shou ld be w ell as p reventing throm bosis. Som e of these agents d o not
referred to a hem atologist for a sp ecific evalu ation for von p rolong the blood coagu lation tim es and their p resence in
Willebrand d isease or a p latelet fu nction d efect. the patient w ould thu s not be recognized u nless appreci-
ated u p on a carefu l review of a p atient’s m ed ication list.
The surgeon need s to be aw are of these agents and their
■ DETERMINING THE DIAGNOSIS OF A p harm acokinetics in p rep aring the p atient for su rgery. In
BLEEDING SURGICAL PATIENT IN THE this section, only cu rrently ap p roved d ru gs w ill be d is-
OPERATING ROOM OR RECOVERY ROOM cu ssed (Table 20.3). In general, anticoagu lants can be classi-
fied into tw o groups: antifibrin agents and antiplatelet
One of the most challenging aspects of consultative medicine agents. Antifibrin agents can be su bclassified into nonspe-
is the emergency telephone call to see to the bleeding patient cific inhibitors and sp ecific inhibitors. The nonsp ecific anti-
in the operating room (OR) or recovery room. It is the job of coagu lants consist of u nfractionated hep arin and w arfarin.
the hemostasis consultant to be certain that the cause of These agents at their usual therapeutic d ose prolong the PT
bleeding is not due to some medical factor(s) that can be cor- and APTT. Unfractionated hep arin (stand ard heparin) has
rected by means other than ad ditional surgery. Although a short half-life (1 to 2 hou rs) allow ing for norm alization of
their problems may be acute, the approach to these patients is bleed ing risk w ithin 4 hou rs after its infu sion is stopp ed .
the same as that for assessing risk for bleeding in the preop- With the excep tion of CPB su rgery u sage, patients on
erative evaluation. The first issue is the documentation of the u nfractionated hep arin need only be d elayed 4 hours once
preoperative variables examined prior to surgery. For exam- stop p ing the d ru g before com m encing w ith the p roced ure.
ple, patients w ith a long medication list could be on anticoag- Ind ivid u als on u nfractionated heparin w ho start to bleed
ulants and/ or antiplatelet agents (e.g., low-molecular-w eight only need red blood cell (RBC) and p lasm a su p port (see the
heparin, warfarin, aspirin, clopidogrel [Plavix®], vitamin E, d iscu ssion below on the effect of m assive transfu sion) for
serotonin release inhibitor antidepressants) that do not neces- the d u ration of tim e they are at risk. Usu ally, su fficient
sarily prolong screening coagulation tests but increase a am ou nts of the d ru g are m etabolized w ithin hou rs to
patient’s risk of bleeding at the time of surgery or postopera- remove the need for ad d itional therap y. Protam ine su lfate
tively. Thus, the surgeon needs to be aware of prior medica- is alm ost never need ed to correct abnorm al bleed ing in an
tion history and its possible role in surgical bleeding. After ind ivid u al on hep arin.
the medications are reviewed, the assessment for other spe- Warfarin therap y, how ever, p resents d ifferent chal-
cific acquired bleeding states proceeds. As mentioned above, lenges. N orm ally, it takes at least 5 d ays to fu lly anticoagu-
acquired bleeding states are usually due to anticoagulation, late som eone on w arfarin. The d elay in anticoagu lating
DIC, liver disease, vitamin K deficiency, or massive transfu- som eone on w arfarin is the resu lt of the fact that the d ru g
sion (Table 20.3) (8,9). Each of these conditions is associated need s to inhibit and alter the synthesis of fou r coagu lation
with a prolonged PT and APTT. p rotein zym ogens (p roenzym es factors II, VII, IX, X) before
its anticoagu lation effect is achieved . Since these targets
have variable half-lives (4 hou rs to 5 d ays), it takes at least
Table 2 0 .3 Acq u ir ed su r gica l bleed in g 5 d ays before a fu ll anticoagu lation effect is achieved . Thus,
Anticoagulation the patient on w arfarin at the tim e of surgery also need s a
Antifibrin agents m inim u m of 5 d ays to correct its anticoagu lation effect.
Unfractionated heparin (standard heparin) Patients on w arfarin shou ld have this m ed ication stopp ed
Low-molecular-weight heparin at least 1 w eek before having elective su rgery. Cu rrent
Fondaparinux p ractice is to continu e to anticoagu late the p atient w ith
Warfarin low -m olecu lar-w eight h ep arin u p to 24 hou rs before th e
Direct thrombin inhibitors: hirudin (Refludan, Leperudin), argatroban, tim e of op eration to p reven t throm bosis (10). Postop era-
bivalirudin (Angiomax) tively, th e p atien t w ill n eed to be treated w ith at least
Antiplatelet agents
5 d ays of p arenteral low -m olecu lar-w eight hep arin if the
Aspirin
risk of early anticoagu lation is w arran ted by the risk of
Clopidogrel
Glycoprotein IIb/IIIa antagonists [Abciximab (ReoPro), tirofiban throm bosis until the reinstituted w arfarin therapy can
(Aggrastat), eptifibatide (Integrilin) becom e effective as an anticoagu lant again. It is appropri-
ate to start anticoagu lation in high-risk patients 12
Disseminated intravascular coagulation—acute
to 24 h after su rgery (10). If su rgery is em ergent w ithin 24 h
Liver disease and the p atient is on w arfarin, there are a few options. In
Vitamin Kdeficiency general, a p atient fu lly anticoagu lated on w arfarin has only
Massive transfusion abou t 5% to 15% norm al activity of coagu lation factors II,
VII, IX, and X. Fu rther, the rem aining 85% to 95% of these
factors is synthesized abnorm ally, and thus acts as a coagu - w eight hep arin and fond ap arinu x are excreted renally.
lation p rotein inhibitor, potentiating the risk to bleed . Since Therefore, p atients w ith renal d ysfu nction have longer
norm al hem ostasis requires normal coagu lation factor lev- clearance tim es. Also, both agents are stored in ad ipose
els to be at least 50%, these patients w ou ld require at least tissu e, allow ing for anticoagu lant accu m u lation in obese
50% or m ore of their plasm a volum e to be replaced . In a p atients. These factors are associated w ith abnormal bleed -
70 kg p erson, p lasm a volu m e is 60% of blood volu me ( 7% ing as result of higher d rug levels than anticipated .
of bod y w eight) or 3 liters plasm a (or 12 units of fresh The d irect throm bin inhibitors, hiru d in, argatroban,
frozen p lasm a [FFP] [1 Unit FFP 250 m L]). If 50% of the and bivaliru d in, are antifibrin agents that interact sp ecifi-
plasm a volu m e need s to be given to the patient to correct cally w ith the throm bin active site, exosite I, or both. All
their hem ostatic d efect, the patient w ou ld require 1.5 liters w ill p rolong the screening tests for coagu lation d isord ers.
of FFP over a very short p eriod of tim e. Most patients and If renal and liver fu nctions are norm al, hiru d in or
blood banks cannot tolerate a replacem ent prescription like bivaliru d in and argatroban are elim inated in 0.5 to 2 hou rs,
this. Thu s, su rgery should be avoid ed at all costs in a resp ectively. Thu s, if a p atient is on these d ru gs, only a
patient fu lly anticoagu lated w ith w arfarin. H ow ever, if short tim e m u st p ass before the p atient can go to su rgery.
truly life saving therapy is need ed in su ch a p atient (e.g., Fu rther, su p p ort for abnorm al bleed ing w ill be for a short
intracerebral hem orrhage in a patient on w arfarin), there tim e. Alternatively, renal d ysfu nction and failu re d elay the
are a few op tions. One w ou ld be to consid er w hole bod y clearance of hiru d in, m aking this recom binant, foreign
plasm a exchange by plasm apheresis. Another w ou ld be to p rotein im p ossible to elim inate. In cases of severe renal
acu tely rep lace the patient w ith a vitam in K coagu lation failu re, even w ith a norm al blood u rea nitrogen and creati-
factor concentrate, if available (11). Third , w ou ld be acu te nine on continu ou s venovenou s hem ofiltration (CVVH ),
replacem ent w ith recom binant factor VIIa (rFVIIa) (12,13). hiru d in can becom e virtu ally im p ossible to elim inate.
Abnorm al bleed ing in all locations other than the central Great care is essential w hen choosing to u se this d ru g in
nervous system (CN S) in patients on w arfarin is corrected d ynam ic clinical situ ations. I generally d o not u se hiru d in
w ith a single d ose of rFVIIa at 20 to 40 g/ kg as a single in m y p ractice.
intravenou s (IV) infu sion along w ith 2 units FFP (12). More In ad d ition to the above list of antifibrin agents,
rFVIIa is not better. Too m u ch rFVIIa that costs $1.00/ g antip latelet agents are increasingly being u sed in clinical
has been reported to be associated w ith m yocard ial infarc- m ed icine (Table 20.3). These agents d o not influ ence the PT
tion or stroke. It has a 3-hour half-life. A second d ose is and APTT, bu t w ill p rolong the bleed ing tim e or PFA-100.
occasionally help fu l. If m ore than tw o d oses are need ed to Asp irin, a p latelet cyclo-oxygenase I and II inhibitor, has
stop bleed ing, a stru ctu ral etiology need s to be looked for. becom e u biqu itou s in the m anagem ent of coronary artery
If there is bleed ing w ithin the sku ll, that is, a closed sp ace, a d isease. A single 80 m g tablet of asp irin interferes w ith
single IV d ose of rFVIIa at 90 g/ kg w ith 2 u nits FFP is p latelet fu nction for all p latelets p resent at the instant w hen
app rop riate to reverse intracerebral hem orrhage in a the agent w as taken. Thu s, after asp irin ad m inistration, the
patient on w arfarin (13). p atient’s p latelet fu nction w ill not becom e norm al u ntil at
In ad d ition to the above nonsp ecific anticoagu lants, least half of the entire platelet pool has been resynthesized
several antifibrin agents are sp ecifically d irected to coagu - (10 to 14 d ays). Patients taking asp irin m ay requ ire platelet
lation factors Xa and throm bin (IIa). All the low -m olecu lar- transfu sions in p lanned or em ergent op erations. Clopid o-
w eight hep arins and fond ap arinu x are mostly d irected to grel (Plavix®) is a p latelet ADP P2Y12 receptor antagonist.
factor Xa and not throm bin. At d oses that are therap eu tic It is also an irreversible p latelet inhibitor. Patients on clopi-
for the treatm ent for d eep venous throm bosis, these agents d ogrel shou ld stop taking the agent before elective su rgery.
may, in variou s ind ivid uals, only slightly prolong the Vitam in E is a protein kinase C inhibitor that interferes w ith
screening tests of the PT and APTT. Therefore, these assays p latelet fu nction. Som e p atients on vitam in E w ill also have
cannot be used to exclu d e the possibility that these agents abnorm al bleed ing at the time of su rgery. Serotonin release
are p resent in the p atient. Although the PT and APTT are inhibitor antid epressants are com m only u sed and all pro-
not m arked ly p rolonged , the risk of bleed ing in p atients d u ce an acqu ired p latelet storage p ool d isord er that
treated w ith low -m olecu lar-w eight hep arin or fond a- increases bleed ing risk. Last, the glycop rotein IIb/ IIIa
parinu x is sim ilar to that for those on unfractionated ( 2b 3 integrin) antagonists are u sed to inhibit p latelets in
hep arin. If hem orrhage occurs, there is no im m ed iate anti- the acu te coronary synd rom e. Althou gh tirofiban or eptifi-
d ote, althou gh rFVIIa infusion cou ld be u sed in cases of batid e is rap id ly excreted w hen its infu sion is stopped , the
seriou s bleed ing (See below ). Low -m olecular-w eight m onoclonal antibod y glycop rotein IIb/ IIIa antagonist,
hep arins have slightly longer half-lives (2 to 4.5 hours) than abciximab, can rem ain in the circu lation system for 15 d ays,
unfractionated hep arin; the half-life d ep end s u pon the w ith the p otential to cau se hem orrhage.
preparation. H ow ever, these agents accum u late, and after
chronic therap y, it w ill take up to 24 hours to com p letely
elim inate them . Fond aparinu x has an 18-hou r half-life, so if
■ Disseminated intravascular coagulation
bleed ing occu rs w hile on this agent, su pport has to be DIC is a clinicop athologic cond ition that arises in patients
given for a longer period of tim e. Both low -m olecu lar- d u e to sep sis, m alignancy, obstetrical com p lications at the
tim e of su rgery, and m assive tissue inju ry. In the su rgery itate or a recently ap p roved p u rified fibrinogen concentrate
patient, DIC is u su ally not a p reoperative variable, excep t is also ind icated . The entire p u rp ose of therapy in these
w ith obstetrical catastrop hes or after major brain trau m a. p atients is to su pport the p atient so that the und erlying
Rather, it is a com plication that occu rs d uring surgery or in cond ition can be brou ght u nd er control. Anticoagu lant
the p ostop erative period . DIC d uring surgery occu rs in a therap y has little role in m ost of these p atients, except in
nu m ber of cond itions. Surgery for prostate cancer and into ind ivid u als w ith acryl cyanosis and d igital ischem ia w here
the brain have been associated w ith acu te DIC. In circu lasm all d oses of hep arin (4 to 5 U/ kg constant infusion w ith-
tory arrest op erations on the arch of the aorta or m ain p u l- ou t a bolu s), m ay am eliorate the p rothrom botic natu re
monary arteries, DIC is a frequent com plication d u e to the of the inciting etiology. H ep arin u sage (u nfractionated
chilling of the p atient to 19 C follow ed by tissu e rew arm - hep arin or low -m olecu lar-w eight hep arin) shou ld only be
ing. Abru p tio p lacenta and placenta p revia are associated u sed if there is an end point in a lim ited d isease state that
w ith acu te hem orrhagic DIC, w hereas retained d ead fetu s need s to be achieved .
is associated w ith a DIC that is not hem orrhagic, bu t p ro-
throm botic. DIC also occu rs in the postoperative p eriod
d u e to sep sis. DIC w ith sepsis is m ost com m only seen w ith
■ Liver disease
gram negative infections, but can occu r w ith gram p ositive It is im portant that surgeons know if a p roposed patient
infections and , in the im mu nosu ppressed patient, w ith has liver d isease. In ad d ition to the anesthesia risk, m ost
fu ngem ia. coagu lation p roteins and inhibitors are m ad e in the liver.
The d iagnosis of DIC is throu gh the p resence of certain Thu s, these p atients have increased risk of bleed ing.
abnorm al clinical test resu lts in an ap propriate clinical set- Patients w ith seriou s liver d isease w ill have p rolonged PT
ting. Find ing a p rolonged PT and APTT w ith a red u ced fib- and APTT. N ot only are the synthesis of these proteins
rinogen and p latelet cou nt u su ally p oints to DIC in the red u ced , bu t those p roteins m ad e are often abnorm al in
hosp italized p atient u ntil p roven otherw ise (14). The d iag- stru ctu re, fu nctioning as inhibitors to norm al coagulation
nosis of DIC is m ad e by a confirm atory test that show s the p roteins. As in p atients on w arfarin, rep lacem ent therapy
sim u ltaneou s p resence of throm bin and p lasm in form a- w ith FFP is not com pletely feasible because too m uch
tion. Cu rrently, the D-d im er assay is the confirm atory test rep lacem ent is u su ally need ed . Also, since this is d epend -
that, if p ositive, show s that both throm bin and p lasm in ent u p on the half-life of the p rotein (e.g., factor VII is only 3
have been form ed . The D-d imer m easu res p lasm in- to 4 hou rs), it is not p ractical to keep u p w ith replacem ent
cleaved , insolu ble, cross-linked fibrin that originally arose need s over long p eriod s (i.e., 12 to 24 hou rs). In ad d ition
from throm bin cleavage of fibrinogen. D-d imer assays are to red u ction in synthesis of coagu lation proteins and
characteristic for DIC, bu t not pathognom onic. D-d im er inhibitors in p atients w ith liver d isease, liver d isease itself
assays can be p ositive in ind ivid uals w ith resolving large results in abnorm al anatom y such as portal hypertension
vessel throm bosis and soft tissu e hem atom as, w hich can that increases patients’ risk of bleed ing from esophageal
also occu r in su rgery patients (15). varices, gastritis, and hem orrhoid s. Fu rtherm ore, portal
Managem ent of DIC first starts w ith recognition of the hyp ertension resu lts in hyp ersp lenism , throm bocytopenia,
synd rom e and treatm ent of the u nd erlying d isease. Treat- and granu locytop enia. In general, p rekallikrein is one of
ment of abru p tio placenta, placenta p revia, or retained the first proteins to d ecrease in liver d isease; fibrinogen is
d ead fetus is rem oval of the inciting etiology by surgical one of the last p roteins to d ecrease in liver d isease. Abnor-
means. DIC associated w ith sepsis is first treated w ith m al fibrinogens (d ysfibrinogenem ias) are very com m on in
rem oval of the inciting infectiou s focu s w ith antibiotics or, p atients w ith liver d isease. All the vitam in K d ep end ent
if ap p rop riate, through su rgical m eans. Once the inciting p roteins (factors II, VII, IX, and X, p roteins C, S, and Z)
cau se is ap p reciated and any specific therapy applied , gen- d ecrease in liver d isease. Factors VIII and V also d ecrease at
eral m ed ical therapy can be provid ed for the DIC. Most late end -stage liver d isease. Moreover, antithrom bin and
cases of DIC associated w ith surgery are hem orrhagic other serp in p lasm a p rotein inhibitors d ecrease in liver d is-
coagulopathies resulting in consu m ption of coagu lation ease. Thu s, these p atients have red u ced p rocoagulants and
factors and p latelets. Thus, therapy should be d irected anticoagu lants, ad ju sting the baseline for hem ostasis at a
tow ard s rep lacem ent of m issing coagu lation factors or level other than that seen in norm al p eop le.
platelets, or both. Each platelet transfusion is bathed in Preop erative m anagem ent of p atients w ith liver d isease
fresh p lasm a. Therefore, platelet infu sion also p rovid es requ ires thou ght w ith regard to a nu m ber of variables. All
som e p lasm a rep lacem ent and ad d itional rep lacem ent w ith these patients should be given vitamin K to ensu re that
FFP m ay not be necessary. The pu rpose of FFP rep lacem ent they are not d eficient. The natu re and d u ration of su rgery
is not only to replace the consu m ed coagulation p roteins, also need s to be consid ered . If it is a short proced u re,
bu t also p rovid e plasm a protease inhibitors, for exam p le, rep lacem ent coverage w ith FFP m ay be su fficient. H ow -
antithrom bin, 2-antiplasm in, C1 esterase inhibitor, and so ever, its d u ration m ay be too short to be effective. If a
on, that red u ce the d egree of active p roteolytic reactions p atient is m ostly d eficient in fibrinogen (i.e., 100 m g/ d L)
occu rring in the plasma. If the fibrinogen levels are low, or the fibrinogen fu nctions abnorm ally, cryop recipitate or
that is, 150 m g/ d L, sp ecific rep lacem ent w ith cryop recip - new ly ap p roved fibrinogen concentrate infu sion m ay be
sufficient to correct the d efect. Alternatively, if the p atient p lasm a from all the transfu sions consp ire to lead to an anti-
has a d ecrease in all factors and is throm bocytop enic, the coagu lated state. Su ch a situ ation occu rs in the OR w hen
most global m eans to treat su ch a patient is w ith p latelet there is vigorou s RBC rep lacem ent. In most circu m stances,
transfu sions, aim ing to keep the platelet cou nt greater than this p roblem can be avoid ed by linking 1 u nit of FFP to
100,000/ L throu ghou t the op erative p roced u re and d u r- every 4 to 6 u nits of RBC transfu sion. In ad d ition, one
ing the first 24 hou rs p ost op eration, su bsequently tap ering am p u le of calciu m shou ld be ad m inistered for every fou r
off slow ly. Finally, if all fails, rFVIIa infusion at 40 to to six u nits of transfu sed RBCs and 1 u nit of FFP to over-
60 g/ kg as a single IV bolus acutely can be used to get a com e the anticoagu lant effect of the sod iu m citrate.
bleed ing d iathesis u nd er control. Again, rFVIIa therap y is
to be u sed w ith cau tion and not rep etitively.
■ Managing massive bleeding
There are tim es in the OR w hen bleed ing occu rs and ap pro-
■ Vitamin K deficiency p riate therapy has been instituted , bu t the su rgeon still
Vitam in K, a lip id soluble vitam in, is provid ed by d ietary believes that hem ostasis has not been achieved in a suffi-
intake of leafy green vegetables and by synthesis of intes- ciently timely manner. In these critical situations, an imme-
tinal flora. The bod y has 1 m onth stores. Vitam in K d efi- d iate, short-term m eans to get a hand le on the hem orrhage
ciency is m ostly seen in the very ill su rgical p atient on is the use of IV infusion of rFVIIa (16,17). Recombinant
antibiotics w ho has subsisted on p arenteral nu trition. N ot FVIIa infusion d irectly activates IX and / or X to lead to
infrequ ently, IV flu id s are not su pplem ented w ith vitam in throm bin form ation. In essence, its infu sion m akes a patient
K. After 4 to 6 w eeks of parenteral nu trition and antibiotic p rothrombotic. H ow ever, life-threatening bleed ing in the
treatm ent, the p atient becom es vitam in K d eficient. Vita- OR m ay requ ire its u se to get control of a situ ation.
min K d eficiency can also be seen in p atients w ho have Although the literature provid es a w id e range of d osing
anatom ic byp ass of the sm all intestine, m alabsorption, bil- that can be used , our experience tells us that a m ore conser-
iary tract obstru ction, and , rarely, red uced d ietary intake. vative d osage from 40 to 60 g/ kg rFVIIa is often sufficient
For exam p le, alcoholics are often vitam in K d eficient. War- to achieve hem ostasis safely in m ost patients w ith an acu te
farin also interferes w ith tw o enzym es necessary for vita- hemorrhage, not immed iately controllable by more trad i-
min K u tilization. Vitam in K has a critical role in the tional m eans. rFVIIa therap y w orks best in ind ivid u als w ho
-carboxylation reaction of glu tam ic acid resid u es, - have been replenished w ith coagulation proteins in FFP.
carboxyglutamic acid , of the so-called vitamin K-d epend ent
coagu lation p roteins, factors II, VII, IX, and X and proteins
C, S, and Z. This reaction on certain am ino acid s on the
■ ASSESSING RISK AND PREVENTION FOR
amino term inu s of these proteins is critical for these p ro-
THROMBOSIS IN THE SURGICAL PATIENT
teins to bind to cells and p hosp holip id s so that they can Although bleed ing in any patient is d ram atic and anxiety
particip ate in p hysiologic coagulation reactions. Vitam in K p rovoking, throm bosis is a silent cau se of m ore m orbid ity
is u su ally rep laced by oral therapy. H ow ever, if necessary, and m ortality. More su rgical p atients d ie of throm botic
parenteral rep lacem ent can be given. Intram uscular rather com p lications resu ltant from su rgery than bleed ing. It is
than IV is the p referred , safe route of ad m inistration. incu m bent u p on the p hysician to be know led geable abou t
the risks for throm bosis that occur in the su rgical patient.
The best treatm ent for throm bosis is throm bosis p reven-
■ Massive transfusion
tion. In general, venou s throm bosis occu rs in areas of low
Bleed ing com plications from m assive transfu sions them - flow and consists of an initial p latelet throm bu s follow ed
selves occu r as resu lt of the am ou nt of anticoagulant being by an accu m u lation of red cells in a fibrin m esh. Alterna-
pou red into the p atient by substantial transfu sion w ithin a tively, arterial throm bu s is m ostly p latelet-rich, occu rring
short p eriod of tim e. Sixteen percent of the volum e of each in areas of high blood flow. Both venou s and arterial
unit of p acked RBCs, p latelets, and FFP consists of acid -cit- throm boses have know n risk factors (18).
rate-d extrose anticoagulant. This anticoagu lant chelates
plasm a d ivalent cations su ch as calciu m , m agnesium , and
zinc, su ch that they cannot participate in the blood protein
■ Arterial thrombosis
coagu lation reactions. If in a 24-hou r p eriod , 1.5 tim es the It is beyond the scope of this chapter to fu lly d iscuss the
patient’s blood volu m e is transfu sed , the accu m ulation of risk factors for m yocard ial infarction and stroke. To d ate,
the citrate anticoagu lant can be m assive, p rod ucing antico- no fu nd am ental cohesive hyp othesis has been form u lated
agulation itself and an acqu ired coagu lopathy. For exam - to u nd erstand a com m on pathw ay for increased arterial
ple, in the 70 kg m an, 7% of bod y w eight or 4.9 kg or liters throm bosis. Both hyp ertension and atherosclerosis are
are the blood volu me. If this ind ivid ual received 1.5 times associated w ith it, bu t “how ” has not been precisely
his blood volu m e, he w as transfu sed 7.35 liters of blood d efined . H ow ever, w e d o know of certain p rotein risk fac-
prod ucts of w hich 1176 m L w as anticoagulant alone. Thu s, tors that contribu te to arterial throm bosis. In p articular, ele-
the anticoagu lant volu m e and d ilu tion of his end ogenou s vation of hom ocysteine and antiphospholipid antibod ies
contribu te to risk of both arterial and venou s throm bosis. Table 2 0 .4 Pr ot ein ba sis for in cr ea sed
Each w ill be d iscussed in the section below on venou s t h r om bosis r isk
throm bosis. Another factor for increased risk for arterial
throm bosis is the elevation of lipoprotein(a) [Lp (a)]. Lp (a) Factor VLeiden (20%–60%)a (activated protein C resistance) (sevenfold
consists of low d ensity lipoprotein (LDL) and ap olipopro- increased risk for VTE)
tein(a). Ap olip op rotein(a) has 98% sequ ence id entity to Elevated homocysteine (10%)
kringle 4 of p lasm inogen, the portion of plasm inogen that
Prothrombin 20210 (6%) (threefold increased risk for VTE)
bind s to cells and phosp holip id s, the place w here clinically
significant throm bolysis occu rs. Therefore, Lp(a) is both Protein C deficiency or defect ( 5%) (75% risk for VTE)b
atherogenic and p rothrom botic. Protein S deficiency or defect (3%–4%) (74% risk for VTE)b
Dysfibrinogenemias (1%–3%)
■ Venous thrombosis Antithrombin ( 1%) (50% risk for VTE)b
Risk factors for venous throm bosis in the surgical patient a

The parenthesis indicates the frequency in patients with VTE.
are nu m erou s. After 2 w eeks of bed rest, there is 20% likeli- b
High risk for VTE.
hood of thrombosis in a 20-year-old ind ivid ual, bu t 60% VTE, venous thromboembolism.
likelihood of throm bosis in a 60-year-old patient. Obesity is
a risk factor for venou s thrombosis in 55% of p atients. A associated w ith other p rothrom botic risk factors. Factor V
preop erative am bulatory patient has a low er risk of throm - Leid en is consid ered a low risk factor for throm bosis. H ow -
bosis than a bed -rid d en ind ivid ual. Further, a patient w ith ever, w hen com bined w ith other risk factors or w hen ind i-
a stroke is m ore likely to have throm bosis in the p aretic vid u als w ith the d efect are p u t in high risk for throm bosis
lim b than in the nonparetic lim b. The su rgical patient w ith situ ations, it can su m m ate w ith the other entities increasing
card iac d isease is m ore throm bus prone than if there w as throm bosis risk. Som e d ata su ggest that p atients w ith the
no card iac d isease. Wom en on oral contraceptives p u t on factor V Leid en d efect m ay have early graft closu re after
bed rest w ill have an greater risk of throm bosis than if they coronary artery byp ass su rgery.
w ere not on contraceptives. Su rgery itself prom otes throm - H om ocysteine ( 10%) is the next m ost com m on entity
bosis. The d egree of risk d epend s on the natu re of the su r- associated w ith increased risk for throm bosis. H om ocys-
gery and the am ou nt of tim e the patient is u nd er teine levels of 11 or greater are a risk factor for card iovascu -
anesthesia. For exam ple, orthoped ic su rgery (hip , knee) is lar d isease. Elevated homocysteine inju ries end otheliu m ,
associated w ith actu al flexing and occlu sion of the fem oral p rod u cing free rad icals, and thu s interferes w ith throm bo-
and p op liteal veins, respectively. The incid ence of d eep p rotective mechanism on vascu lar end otheliu m and pro-
venou s thrombosis is 35% to 40% and 50%, respectively. In m otes atherosclerosis. Patients w ho have elevations in
abd om inothoracic su rgery, the risk of throm bosis is 14% to hom ocysteine shou ld be treated w ith oral folate. The third
35%. In u rologic surgery, the risk of a d eep venou s throm - m ost com m on risk factor for increased throm bosis risk is a
bosis is 7% for a transurethral resection, but 35% for a gene m u tation in p rothrombin, p rothrom bin 20210 ( 6%).
sup rap u bic p rostatectom y. Sim ilarly, in gynecologic su r- This p olym orp hism in the 3’ u ntranslated region of the
gery, a vaginal hysterectom y has a 7% risk of throm bosis p rothrom bin gene p rod u ces increased am ou nts of a norm al
bu t a total abd om inal hysterectom y, 27%. Last, su rgical p rothrom bin, thu s tip p ing the balance tow ard s a pro-
patients w ith m alignancy have a higher risk of throm bosis throm botic state. Like factor V Leid en, both elevations of
as resu lt of their m alignancy itself. This risk can m anifest hom ocysteine and the p rothrom bin 20210 m utation are
itself years before the clinical presentation of the cancer. w eak isolated risk factors for throm bosis. H ow ever, w ith
In ad d ition to these situ ation cau ses for throm bosis, su rgery, their im p ortance su m m ates.
there are now a nu m ber of recognized p rotein d efects that More serious, but less common, protein d efects associ-
increase the risk of throm bosis in surgical patients (Table ated with thrombosis are protein C ( 5%) and S (3% to 4%)
20.4). The im p ortance of recognizing these cond itions p re- d eficiencies (Table 20.4). These protein d efects interfere w ith
op eratively is that in the affected p atient sp ecial attention the major anticoagulant function of the protein C and S sys-
to throm bosis risk at the tim e of su rgery and p ostop era- tems. Patients w ith these protein d efects and a history of
tively m ay tem per the risk. By far, the m ost com m on thrombosis m ay require life-long anticoagulation since they
molecu lar d efect associated w ith thrombosis is the factor V have a 75% risk of having venous thromboembolism. Abnor-
Leid en nu cleotid e polym orphism (20% to 60% of p atients mal fibrinogens (d ysfibrinogens) are a heterogeneous group
w ith venou s throm boem bolism , VTE) (G to A m u tation at of d isord ers, som e of w hich carry an increased risk of throm-
base p air 1691 of coagu lation factor V) that resu lts in a p ro- bosis. Antithrombin deficiency or defects give a very serious
tein that is resistant to activated protein C inactivation (i.e., prothrombotic risk w ith a 50% likelihood of having venous
activated p rotein C resistance) (19,20). The factor V Leid en thromboembolism. Fortunately, these patients are quite rare
d efect is the m ost com m on inherited cau se of throm bosis in and constitute less than 1% of all patients seen with throm-
w estern p op u lations, approaching 20% of u nselected cases bosis. Recognition of this d efect in a patient w ith thrombosis
and 60% of cases w ith fam ily histories (21). Fu rther, it is requires life-long anticoagulation.
Table 2 0 .5 M ed ica l/h em a t ologic con d it ion s need s to be taken to p revent it from occu rring. The rare
a ssocia t ed w it h in cr ea sed r isk for hem atologic cond itions of throm botic throm bocytop enic
t h r om bosis p u rp u ra (TTP), a d eficiency or antibod y to the von
Willebrand factor cleaving enzyme, ADAMTS13 (a d isinte-
Disseminated intravascular coagulation grin and m etallop roteases w ith a throm bospond in-1-
Heparin-induced thrombocytopenia and thrombosis syndrome like d om ain), and hem olytic u rem ic synd rom e (H US),
Antiphospholipid syndrome d u e to Shiga toxin from Escherichia coli 0157:H 7, present
w ith severe throm bocytop enia and a m icroangiop athic
Thrombotic thrombocytopenic purpura
hem olytic anem ia. Usu ally, these p atients are exclud ed
Hemolytic-uremic syndrome from su rgical intervention. Last, myelop roliferative d isor-
Myeloproliferative disorders d er su ch as p olycythem ia vera and essential throm bocyto-
sis are cond itions w ith elevated platelet cou nts and a high
increased risk for throm bosis. A m ajority of these ind ivid u-
als have a p olym orp hism in JAK2V617F resu lting in consti-
In ad d ition to the m olecu lar/ p rotein d efects that tu tive overp rod u ction of RBCs and / or p latelets. Prior to
increase a p atient’s risk o throm bosis, certain m ed ical su rgery, efforts shou ld be m ad e to red u ce the elevated
cond itions are also associated w ith throm bosis. The su r- p latelet or RBC cou nts as w ell as p rovid e generou s prop hy-
geon need s to be aw are of these cond itions as w ell so that laxis for thrombosis since these p atients have a 30% to 40%
sp ecial p recau tions can be m ad e to p rotect these p atients risk for VTE.
from throm bosis at the tim e of elective or em ergent su r-
gery (Table 20.5). As m entioned above, DIC can be associ-
ated w ith throm bosis. If DIC is seen in a p atient w ith
■ Therapy for thrombosis and its prevention
m alignancy, sp ecial effort is necessary to p revent venou s The best therap y in the p atient at increased risk for throm -
throm bosis that can occu r in these ind ivid u als. Best p re- bosis is its p revention. In trial of 4,121 p atients u nd ergoing
vention for throm bosis in the cancer p atient is p rop hy- m ajor su rgical p roced u res, the u se of low d ose u nfraction-
laxis w ith low -m olecu lar-w eight hep arin (22). Another ated hep arin resu lted in a red u ction of d eep venou s
m ed ical cond ition p red isp osing to throm bosis is hep arin- throm bosis to only 7.7% of p atients versu s 24.6% of
ind u ced throm bocytop enia and throm bosis synd rom e p atients in the u ntreated control grou p (23). This land m ark
(H ITTS). This entity is m ost com m only seen in p atients stu d y in 1975 established the need for d eep vein throm bo-
w ho have had CPB. A very high p ercentage of p atients sis (DVT) p rop hylaxis in the su rgical p atient. This stu d y
after CPB w ill have antibod ies that are p ositive to w as rep eated w ith low -m olecu lar-w eight hep arin show -
hep arin. Also, abou t 1% and 2.5% of p atients w ho get ing the sam e as u nfractionated hep arin (24). In the United
d eep venou s throm bosis p rop hylaxis w ith low -m olecu lar- States, Med icare recognized that this w ell-d ocu m ented
w eight hep arin or u nfractionated hep arin, resp ectively, treatm ent w as u nd eru tilized . It institu ted a p olicy of no
w ill d evelop H ITTS anyw here from 3 to 14 d ays after hosp ital reim bu rsem ent for m anagem ent costs of a p ost-
com p letion of therap y. Any p atient w ho p resents w ith op erative venou s throm bosis or p u lm onary em bolism if
new throm bosis p ostop eratively and w ho received p ro- the p atient had not p reviou sly received p rop hylactic anti-
p hylactic hep arin therap y has to be consid ered to have coagu lation. It is beyond the scop e of this chap ter to d is-
H ITTS u ntil p roven otherw ise. When recognized , these cu ss the p ros and cons of su bcu taneou s hep arin or
p atients are treated w ith w ithd raw al of the hep arin and low -m olecu lar-w eight hep arin versu s com p ression stock-
anticoagu lation w ith an alternative anticoagu lant su ch as ings to p revent p ostop erative DVT in su rgical p atients.
argatroban or bivaliru d in. Both ap p roaches have m erit. In p rep aration for su rgery,
Antip hospholipid antibod y synd rom e is another entity the p atient on anticoagu lants shou ld have their oral anti-
that increases throm bosis risk in surgical patients. These coagu lant, w arfarin, stop p ed 5 to 7 d ays before su rgery
patients can have both arterial and venou s thrombosis. The (10). In its p lace, su bcu taneou s low -m olecu lar-w eight
cond ition is recognized by evid ence of antip hosp holip id hep arin shou ld be ad m inistered u p to 24 hou rs p rior to
antibod ies as d eterm ined by m easu ring antibod ies to anti- su rgery (10). Likew ise, as soon as the su rgeon d eterm ines
card iolip in or 2-glycop rotein I and stu d ies for lu p u s anti- that the risk for p ostop erative bleed ing has p assed , u su -
coagu lants, su ch as the confirm atory test for the d ilu te ally 12 to 24 hou rs p ostop eratively, su bcu taneou s low -
Ru ssell’s vip er venom tim e (d RVVT). The d iagnosis of m olecu lar-w eight hep arin shou ld be started on the p atient
antiphosp holip id antibod y synd rom e is m ad e by any one w ith increased throm bosis risk (10). If DVT arises in the
of these 3 assays that are positive for a m inim u m of p ostop erative p atient, therap y shou ld p roceed based u p on
3 m onths w hen tested tw ice. Antiphospholipid antibod ies cu rrent treatm ent p rotocols for all DVT p atients (25). The
interfere w ith the anticoagulant natu re of annexin II, p re- u se of vena cava u m brellas shou ld be reserved for the rare
venting it from getting to end othelial cell m em branes to p atient w ho cannot tolerate fu ll anticoagu lation (e.g.,
red u ce throm bin form ation. Patients w ith antiphosp ho- active gastrointestinal or GI bleed ) in the p ostop erative
lipid antibod ies are prone to throm bosis and , thu s, care p eriod . In the p atients w ho requ ire vena cava u m brellas,
requ ests for rem ovable filters shou ld p referentially be 10. H irsh J, Gord on G, Albers GW, et al. Execu tive su m m ary: Am erican
College of Chest Physicians evid ence-based clinical p ractice gu id elines
m ad e since the p resence of the u m brella itself w ill requ ire (8th Ed ition). Chest 2008;133:71–109.
life-long anticoagu lation (10). 11. Bou lis N M, Bobek MP, Sch m aier AH , et al. Use of factor IX com p lex
in w arfarin -related in tracran ial h em orrh age. Neurosurgery 1999;45:
1113–1118.
■ SUMMARY 12. Deveras RAE, Kessler CM. Reversal of w arfarin-ind u ced excessive
anticoagu lation w ith recom binant hu m an factor VIIa concentrate. Ann
Evaluation of the su rgery patient for bleed ing and throm - Intern Med 2002;137:884–888.
13. Lin J, H anigan WC, Tarantino M, et al. The u se of recom binant acti-
bosis risk follow s from the sam e kind of evalu ation of any vated factor VII to reverse w arfarin-ind u ced anticoagu lation in
patient for bleed ing and throm bosis. Cu rrent d iagnostic patients w ith hem orrhage in the central nervous system : prelim inary
tools are good for assessing bleed ing risk; throm bosis risk, find ings. J Neurosurg 2003;98:737–740.
14. Colm an RW, Robboy SJ, Minna JD. Dissem inated intravascu lar coagu -
on the other hand , requires a good know led ge of the lation (DIC): an ap proach. Am J Med 1972;52:679–689.
patient’s history as w ell as the natu re of the surgical situ a- 15. Rectenw ald JE, Myers DD, H aw ley AE, et al. D-d im er, P-selectin and
tion the p atient w ill be in. Much inform ation is available to m icroparticles: novel m arkers to pred ict d eep venous throm bosis.
Thromb Haemost 2005;94:1312–1317.
gu id e the su rgeon in d iagnosis and therapy. As in all situ a- 16. Mid athad a MV, Mehta P, Waner M, et al. Recom binant factor VIIa in
tions, attention to history and sim p le laboratory assays the treatm ent of bleed ing. Am J Clin Pathol 2004;121:124–137.
makes a d ifference in provid ing care to our patients. 17. Bijsterveld N R, Moon s AH , Boekh old t M, et al. Ability of recom bi-
nant factor VIIa to reverse the anticoagu lant effect of the p entasac-
ch arid e Fon d ap arin u x in h ealthy volu n teers. Circulation 2002;106:
■ REFERENCES 2550–2554.
18. Schm aier AH . Evaluation of throm bosis. In: Schm aier AH , Petru zzelli
1. Davies E, Ratnoff OD. Waterfall sequ ence for intrinsic blood coagu la- LM, ed s. Hematology for the medical student, 1st ed . Philad elp hia: Lip p in-
tion. Science 1964;145:1310–1320. cott, William s & Wilkins; 2003:121–126.
2. Schm aier AH . Princip les of hem ostasis. In: Schm aier AH , Petruzzelli 19. Svensson PJ, Dahlback B. Resistance to activated p rotein C as a basis
LM, ed s. Hematology for the medical student, 1st ed . Baltim ore: Lipp infor venou s throm bosis. N Engl J Med 1994;330:517–522.
cott, William s & Wilkins; 2003:71–77. 20. Greengard JS, Eichinger S, Griffin JH , et al. Brief rep ort: variability of
3. Gailani D, Broze GJ. Factor XI activation in a revised m od el of blood throm bosis am ong hom ozygou s siblings w ith resistance to activated
coagu lation. Science 1991;253:909–912. protein C d u e to an Arg-Gln m u tation in the gene for factor V. N Engl J
4. Sm ith SA, Mu tch N J, Baskar D, et al. Polyp hosp hate m od ulates blood Med 1994;331:1559–1562.
coagu lation and fibrinolysis. Proc Natl Acad Sci U S A 2006;103:903–908. 21. Bavikatty N R, Killeen AA, Akel N , et al. Association of the p rothrom -
5. Kannem eier C, Shibam iya A, N akazaw a F, et al. Extracellu lar RN A bin G20210 A m u tation w ith Factor V Leid en in a m id w estern Am eri-
constitu tes a natural p rocoagu lant cofactor in blood coagu lation. Proc can pop ulation. Am J Clin Pathol 2000;114:272–275.
Natl Acad Sci U S A 2007;104:6388–6393. 22. Lee AY, Levine MN , Baker RI, et al. Rand om ized com p arison of low
6. Maas C, Govers-Riem slag JW, Bou m a B, et al. Misfold ed p rotein acti- m olecu lar-w eight heparin versus oral anticoagulant therapy for the
vate factor XII in hu m ans, lead ing to kallikrein form ation w ithout initi- prevention of recu rrent venous throm boem bolism in patients w ith
ating coagulation. J Clin Invest 2008;118:3208–3212. recu rrent venous throm boem bolism in p atients w ith cancer. N Engl J
7. Schm aier AH . Laboratory evalu ation of hem ostatic and throm botic d is- Med 2003;349:146–153.
ord ers. In: H offm an R, Benz EJ, Shattil SJ, et al. ed s. Hematology basic 23. Kakkar VV, Corrigan TP, Fossard DP, et al; An International Mu lticen-
principles and practice, 5th ed . Philad elp hia: Chu rchill Livingstone tre Trial Grou p. Prevention of fatal p ostop erative p u lm onary em bolism
Elsevier; 2009:1877–1884. by low d oses of hep arin. Lancet 1975;II:46–51.
8. Schm aier AH . Acqu ired d isord ers of blood coagu lation. In: H u m es 24. Kakkar VV, Boeckl O, Boneu B, et al. Efficacy and safety of a low -
H D, ed . Kelley’s textbook of internal medicine, 4th ed . Philad elphia: m olecular-w eight heparin and stand ard unfractionated heparin for pro-
Lipp incott, William s & Wilkins; 2000:1718–1723. phylaxis of postoperative venous thromboem bolism : European m ulti-
9. Schm aier AH . Acqu ired bleed ing d isord er. In: Schm aier AH , center trial. World J Surg 1997;21:2–9.
Petruzzelli LM, ed s. Hematology for the medical student, 1st ed . Philad el- 25. Bates SM, Ginsberg JS. Treatm ent of d eep -vein throm bosis. N Engl J
p hia: Lip pincott, William s & Wilkins; 2003:99–104. Med 2004;351:268–277.
CHAPTER
21
Complications of Nutritional Support

Imad F. Btaiche, Eiichi Miyasaka, and Daniel H. Teitelbaum
N u tritional su p p ort can be p rovid ed by intravenou s (p ar- anastomotic leakage, hepatic and renal failure, and length of
enteral) or gastrointestinal (enteral) d elivery of nu trients. hospital stay (1). Data for PN support is much less clear. The
In general, enteral nu trition is less com plicated and p refer- first definitive study to approach this question was the Vet-
able. H ow ever, the d evelopm ent of parenteral nu trition eran’s Administration (VA) cooperative study, which examined
(PN ) w ithin the last fou r d ecad es has allow ed critical nu tri- a large number of malnourished patients who required major
tional sup port for m any patients. abdominal or thoracic operations (2). Patients were random-
ized to preoperative PN (along with a short course of postop-
■ PARENTERAL NUTRITION erative PN) versus surgery w ithout any PN . Surprisingly,
those patients who received PN had higher rates of infectious
PN is the ad m inistration of com plete and balanced nu tri- complications, including pneumonias, urinary tract infec-
tion via the intravenous rou te to sup port anabolism and tions, and wound infections. The only patients w ith proven
w eight maintenance or gain w hen the gastrointestinal tract benefit from perioperative PN were the ones with severe
cannot or should not be used . Ad equate nutrition is essen- malnutrition. A meta-analysis of patients receiving PN in the
tial for patient recovery, and PN is a life-saving therapy in perioperative period showed that PN was associated w ith a
patients w ith intestinal failure. Conversely, a lack of ad e- 10% increase in the absolute rate of postoperative complica-
quate nutrition may lead to a d ecline in w ound healing and tions (3). This finding w as confirmed by a more recent meta-
possibly an increase in perioperative complications. H ow - analysis of critically ill adults, w hich demonstrated only a
ever, PN can be associated w ith many complications, marginal benefit of preoperative PN in mildly or moderately
includ ing metabolic, infectious, and technical. Asid e from malnourished patients (4). A benefit of preoperative PN w as
the d elivery of PN , good nu tritional care requ ires careful noted only in those patients who were severely undernour-
assessm ent of the patient’s nutritional status and a d etermi- ished . The European Society of Parenteral and Enteral Nutri-
nation of w hich patients should , or should not, receive PN . tion (5) guid elines d efine severe und ernutrition to exist when
one of the following criteria are present: weight loss 10% to
■ Indications for parenteral nutrition 15% w ithin 6 months, body mass ind ex (BMI) 18 kg/ m 2,
in surgical patients subjective global assessment (SGA) Grad e C (See section
below, visible somatic muscle wasting), or serum albumin
PN is indicated when the gastrointestinal tract cannot be
3 g/ dL (with no evidence of hepatic or renal dysfunction)
fully used. This includ es patients w ith significant peritonitis,
(5). The cause of these increased infections has not been
lack of adequate intestinal length, or a malabsorptive state.
definitively determined. How ever, these stud ies have had a
Additionally, patients with specific gastrointestinal disor-
dramatic effect in reducing the aggressive use of PN in surgi-
ders, includ ing intractable diarrhea, protracted vomiting,
cal patients, confining the preoperative use to those patients
enterocolitis, motility disorders, inflammatory bow el disease,
with severe malnutrition.
enteric fistulae with high output, and bowel obstruction may
require parenteral feedings for a prolonged length of time.
Indications for Postoperative Nutrition
Indications for Preoperative Nutrition
Use of aggressive postoperative nu tritional supp ort is even
In adults, provision of enteral feedings preoperatively for 2 m ore controversial (6). In ad u lts, the p rovision of enteral
to 3 w eeks may reduce postoperative w ound infections, nu trients m ay red u ce the rate of sep sis and m ay low er
costs. H ow ever, enteral intolerance can lim it the ability to
Imad F. Btaiche: Departm ent of Pharm acology, University achieve com p lete nu tritional su p p ort (7). These d ata sug-
of Michigan H ealth System s Eiichi Miyasaka: Section of Ped i- gest that, w hen ind icated , p ostop erative nu trition shou ld
atric Su rgery, C.S. Mott Child ren’s H osp ital, University of be started early, u tilizing a com bination of PN and enteral
Michigan Daniel H. Teitelbaum: Section of Ped iatric Su rgery, nu trition u ntil the gastrointestinal tract fu lly recovers. The
C.S. Mott Child ren’s H osp ital, University of Michigan, Ann effect of PN on p ostop erative healing is also u nclear, as
Arbor, MI 48109-5245 m any stu d ies are contrad ictory. Becau se resu lts in the area
210
Chapter 21 • Complications of Nutritional Support 211
of p ostop erative nutritional sup port are not clear, aggres- ered an ind ex of protein d epletion and has been show n to be
sive p ostop erative feed ings are recom m end ed only in associated w ith an increased rate of postop erative mortality
those p atients w ho can receive enteral nu trition w ithou t (12). Unfortunately, low serum albumin levels are not a
com p lication. Postoperative PN should be restricted to good ind icator of nutritional statu s and may lead to incor-
those p atients w ho w ill not start enteral nu trition for at rect classification of the nutritional statu s (13). Serum p real-
least 5 to 7 d ays and w hen PN therapy is expected for at bu min levels may offer the ad vantage of a shorter half-life
least 7 d ays (8,9). In m alnou rished ad u lt patients w hen as compared to albumin (abou t 2 d ays vs. 20 d ays, respec-
enteral nu trition is not p ossible, PN shou ld be started 5 to tively) and thus respond more quickly to nutritional
7 days before elective surgery and continued postoperatively changes. Similar to albumin, prealbumin is a negative acute
until ad equ ate oral or enteral feed ing can be achieved (9). phase protein and its sensitivity and specificity is affected
by stress and other d iseases (14). It is reasonable, how ever,
■ NUTRITIONAL ASSESSMENT to measure serum prealbumin levels once w eekly and fol-
low their trend as a m arker of ad equ ate anabolism and
AND MONITORING
nu tritional repletion in response to nu trition su pport. A
As stated earlier, m any patients w ho requ ire operative more reliable mod ality to d efine malnutrition is the use of a
intervention su ffer from m alnu trition d ue either to a variety baseline SGA. Su ch an assessment is easy to obtain and has
of feed ing d isord ers or to the und erlying d isease for w hich a high d egree of reliability w ith regard to the d etermination
they w ill need surgery. N utritional assessment is a critical of d egree of malnu trition (15). An SGA consists of a history
aspect of the initial evaluation of all su rgical patients, and and physical examination and should inclu d e an evalu ation
the incid ence of malnutrition in surgical patients has been of w eight loss (10% for severe malnu trition), anorexia, or
w ell d ocumented in several review s. In one review by vomiting, as w ell as physical evid ence of muscle w asting.
Mu llen et al., 95% of all surgical patients had one abnormal Patients at p articu lar risk for malnutrition inclu d e those
nu tritional param eter and 35% had three ind icators of m al- w ith large open w ound s w ith the concomitant loss of pro-
nu trition (10). In ad d ition to ad u lts, p ed iatric su rgical tein and increased metabolic need s, extensive burns, blunt
patients m ay also be at risk for malnu trition. Cameron et al. trauma, and sepsis.
show ed that the prevalence of chronic m alnutrition w as
similarly high at 65%, and the incid ence increased to 80% in
card iac surgical infants (11). Clearly, recognizing and cate- ■ MALNUTRITION
gorizing the severity of the malnourished state is the best
w ay to d etermine w hich patient w ill require perioperative
■ Kwashiorkor and marasmus
nu trition su pport. Recognition and correction of malnutri- Classically, m alnu trition has been d ivid ed into tw o basic
tion prior to elective surgery may eliminate or red uce the form s, p rotein-calorie m alnu trition, or m arasm u s, and pro-
rates of surgical morbid ity and mortality. Although a signif- tein d eficiency, or kw ashiorkor (Table 21.1). Althou gh these
icantly m alnou rished patient can easily be id entified , cond itions are m ost p revalent in third -w orld cou ntries,
patients w ith mild to mod erate malnu trition are frequ ently they m ay also be m anifested in hosp italized patients. The
d ifficult to id entify. Classically, ind icators of malnutrition m ost com m on clinical exam p le of a m arasm ic p atient is one
have relied on biochem ical and physical param eters. These w ho has been consum ing an inad equ ate d iet for a p eriod of
have inclu d ed m easu rem ents of albu m in and m orphom et- several w eeks to m onths. A com m on exam p le w ould be an
ric measurements, includ ing triceps skin fold and forearm eld erly ind ivid u al w ho receives little su p p ortive care, often
circumferences. H ypoalbuminemia has long been consid - one w ith a d ep ressed m ental cond ition. Su ch a p atient, if
Table 2 1 .1 Com p a r ison of m a r a sm u s a n d k wa sh ior k or

Disease Clinical Setting Time to Develop Clinical Features Laboratory Clinical Course Mortality
Marasmus T Calorie intake Months or years Starved appearance, Possible normal Reasonably preserved Low, unless
weight 80% of albumin and responsiveness to related to
UBW, TSF 3 mm, transferrin short-term stress underlying
MAMC 15 cm disease
Kwashiorkor T Protein intake Weeks Well-nourished Low albumin and Poor wound healing High
during stress appearance, easy transferrin decubitus
hair pluckability, ulcers, skin
edema breakdown
UBW, usual body weight; TSF, triceps skin fold; MAMC, midarm muscle circumference.
From Khalidi N, Btaiche IF, Kovacevich DS, eds. The parenteral and enteral nutrition manual, 8th ed. Ann Arbor, MI: The University of Michigan Hospitals and Health Centers; 2003.
ad m itted and d ep rived of any nutritional support, w ill ■ Efficacy of correcting malnutrition
begin to u tilize the rem aining som atic m u scle to su p p ort
glu coneogenesis (form ation of glu cose from noncarbohy- It is im p ortant to note that althou gh p neu m onia and respi-
d rate sou rces). In this case, the patient w ill d evelop a m ixed ratory failu re are the m ajor cau ses of d eath for p ersons w ho
picture of an acu te kw ashiorkor state over a baseline state are starved , there is little evid ence that nu tritional repletion
of m arasmu s. The outcom e of such patients is notoriou sly im p roves p u lm onary fu nction and p revents p neu m onia
poor (16). Com m on settings in w hich su ch cond itions can (21). One of the best controlled stu d ies to su ggest that early
occur or be aggravated are in the septic, severely bu rned , or nu tritional su p p ort m ay help su rgical p atients is by
mu ltip le trau m a p atients. These patients m ay lose as m u ch Sand strom et al. (22). In this stu d y, p atients w ere rand om -
as 30 g of nitrogen/ d ay, the equ ivalent of 2.5 lb of w et m u s- ized to receive p ostop erative PN versu s intravenou s d ex-
cle w eight loss d aily. Along w ith this loss of m uscle m ass trose. Patients w ho d id not initiate enteral intake p rior to
w ill be a nu m ber of ad verse com p lications w hich d irectly 14 d ays and w ho w ere rand om ized to receive only d extrose
affect the ou tcom e for surgical patients. had a 10-fold higher m ortality and a tw o-fold higher rate of
sep sis. H ow ever, those p atients w ho received PN and w ere
overfed actu ally had a w orse ou tcom e. Thu s, ju d iciou s u se
■ Complications of malnutrition of p eriop erative nu trition is critical. In fact, based on m eta-
Impaired healing can result from severe states of malnutri- analyses, correction of m alnu trition is ind icated only for
tion and potentially lead to d isruption of intestinal anasto- severely m alnou rished su rgical p atients (23). Overly
moses as w ell as w ound d ehiscence and infection. Previous aggressive u se of PN m ay lead to a m u ch higher incid ence
stud ies have show n d ecreased tensile strength of intestinal of com p lications. In fact, a m eta-analysis of the rou tine use
anastomoses in malnou rished rats, w hich could be pre- of p ostop erative PN su p port su ggests that PN is associated
vented by PN repletion. An effort should be mad e, w hen w ith a 10% increase in com p lications (3). Althou gh PN has
possible, to minimize imp aired w ou nd healing by preoper- nu m erou s associated com p lications, enteral nu trition is
atively nu tritionally repleting patients w ho are severely associated w ith several com p lications as w ell. In a d etailed
und ernourished and by preventing postoperative starva- m eta-analysis com p aring enteral nu trition and PN , no
tion. Zinc, vitamin C (ascorbic acid ), and vitamin A d eficien- ad vantage w as noted other than that the cost of enteral
cies may also lead to impaired w ound healing and should nu trition w as ten tim es low er (24).
be corrected . Malnu trition may also lead to an increased
risk of respiratory d ifficulties, such as atelectasis and pneu- ■ METABOLIC COMPLICATIONS OF
monia, second ary to d ecreased strength of respiratory mus-
PARENTERAL NUTRITION
cles and the inability to cough. The lack of muscle strength
probably d ecreases the p atient’s forced vital capacity and Ju st as m alnu trition m ay lead to a nu m ber of p roblem s
tid al volume and , therefore, prolongs the need for intuba- w ith p eriop erative morbid ity, u se of PN m ay be equally or
tion and mechanical ventilation w ith their associated com- m ore d eleteriou s. Thu s, u se of PN requ ires an extensive
plications of p neum othorax, baro-trau ma, tracheal stenosis, u nd erstand ing of ind ications of PN , know led ge of p roper
and sepsis. Early and , if possible, preoperative nu trition p rescribing, and carefu l m onitoring.
support is ind icated in the malnourished patient. In criti-
cally ill patients w ith a functional gastrointestinal tract,
enteral nutrition shou ld be started early, w ithin 24 to 48
■ Hyperglycemia
hours of ad mission to the intensive care unit (ICU), and H yp erglycem ia is the m ost com m on com p lication associ-
then ad vanced to the nutritional goal over the next 48 to 72 ated w ith PN . Dextrose infu sion rate and the patient’s
hours as p atients are hem od ynam ically stabilized . Early u nd erlying cond itions d eterm ine carbohyd rate tolerance.
enteral nu trition in critically ill patients has been show n to Dextrose oxidation is red uced under stress, such as in criti-
red uce infectious complications (9). Several investigators cally ill and surgical patients (25). Predisposing factors to
have fou nd a m arked increase in septic com plications in hyperglycemia also include sepsis, multiorgan failure, dia-
malnou rished patients (17). Und ernutrition alone resu lts in betes, acute pancreatitis, and drug therapy that alters glucose
d epressed T-lymphocyte numbers and function (18). metabolism (e.g., corticosteroid s, tacrolimus, catecholamine
Impaired leukocyte function could increase the risk of vasopressors).
pneumonia. Recent stud ies suggest that severe malnu trition Stress-ind u ced hyp erglycem ia is the resu lt of increased
can cause breakd ow n of the intestinal mucosal barrier to end ogenou s glu cose p rod u ction in resp onse to increased
bacteria w ith bacterial translocation from the gut lu men to release of counter-regulatory horm ones and cytokines that
the portal venous system (19,20). N eutropenia has also been stim u late glycogenolysis and glu coneogenesis. In stressed
noted w ith copper d eficiency, and im p aired neu trophil p atients, elevated insu lin levels fail, how ever, to su ppress
chemotaxis and phagocytosis have also been found w ith glu coneogenesis or to increase cellu lar glu cose u p take,
phosp hate d eficiency. Imp aired bod y d efenses w ill increase w h ich resu lts in h yp erglycem ia. In a sm all stu d y grou p
the risk of pneumonia, w ound infections, and intracavitary (n 5) of low stress p ostop erative ad u lt p atients, d extrose
abscesses. infu sion rates u p to 7 m g/ kg/ m in w ere tolerated (26).
Table 2 1 .2 Con seq u en ces of over feed in g had red u ced acute renal failure and ventilator d epend ency.
Benefits of intensive insu lin therap y on red u cing m ortality
Source of Overfeeding Consequences w ere notable in the long-stay ICU p atients ( 5 d ays) (38).
Total calories Hepatic steatosis; cholestasis; respiratory A follow -u p m ultivariate logistic regression analysis of
decompensation resu lts show ed that benefits d erived from intensive insu lin
Dextrose Hyperglycemia; hypertriglyceridemia; therap y w ere the resu lt of norm oglycem ia rather than the
hepatic steatosis; hypercapnia; increased insu lin d ose. Also, a d irect correlation w as found betw een
infection risk blood glu cose concentrations and hosp ital m ortality. In the
Lipid emulsions Hyperlipidemia; hypertriglyceridemia; long-stay patients the cum u lative hospital m ortality w as
hepatic steatosis 15% in p atients w ith m ean blood glu cose concentrations
110 m g/ d L, abou t 27% in those w ith m ean blood glucose
concentrations betw een 110 and 150 m g/ d L, and 40% in
patients w ith mean blood glu cose concentrations 150 mg/
H ow ever, d ata from hyperm etabolic ad ult burn p atients d L (39). These d ata su ggest that even sm all red uctions in
sh ow ed a m a xim u m toler able glu cose in fu sion r ate of blood glu cose m ay have a significant effect on im p roving
5 m g/ kg/ min (27). Even low er rates 4 m g/ kg/ min in p atient ou tcom es. H ow ever, the benefits of tight glu cose
stressed ad u lt p atients are better tolerated . In a retrosp ec- control that w ere d erived from the Van d en Berghe stud y
tive review of 102 nond iabetic ad u lt patients w ho received w ere not rep licated in the N orm oglycemia in Intensive
PN , hyp erglycem ia occu rred in 49% of patients w ith d ex- Care Evalu ation—Su rvival Using Glu cose Algorithm Reg-
trose infu sion rates 5 mg/ kg/ m in, and 11% of p atients u lation (N ICE-SUGAR) stu d y. The N ICE-SUGAR stud y
d eveloped hyperglycem ia w ith d extrose infu sion rates w as a large, m u lticenter, p rosp ective, p arallel group,
betw een 4.1 and 5 m g/ kg/ m in. N one of the patients w ho u nblind ed , rand om ized , controlled stu d y of 6,104 m ed ical
received d extrose infu sions 4 mg/ kg/ m in had hyp er- and su rgical ad u lt p atients ad m itted to the ICUs of 42 inter-
glycem ia (28). national hosp itals. Patients w ere enrolled in the stu d y if
H yperglycemia, if left untreated , can result in serious they w ere exp ected to requ ire at least 3 d ays of ICU stay.
complications, includ ing fluid and electrolyte imbalances, Patients w ere rand om ized to an intensive glu cose control
hyperglycem ic hyperosm olar nonketotic com a, and grou p w ith a goal of seru m glu cose concentrations of 81 to
increased infectiou s risk (see Table 21.2). In vitro and anim al 108 m g/ d L or a conventional grou p w ith a goal of seru m
stu d ies have show n that hyp erglycem ia can im p air neu - glu cose concentrations of 180 m g/ d L or less. Stu d y results
trop hil chem otaxis and ad hesion, red uce phagocytosis, and show ed a significantly higher 90-d ay m ortality rate (pri-
inhibit com p lem ent fixation (29,30). Poorly controlled d ia- m ary end p oint) in the intensive glu cose control grou p as
betics have show n im paired p olym orphonuclear leu cocyte com p ared w ith the conventional grou p (27.5% vs. 24.9%,
fu nction (31) and red uced bactericid al activity (32), w ith resp ectively). Fu rther, there w as no benefit from intensive
phagocytic fu nction im p roving w ith glycem ic control (33). glu cose control on second ary and tertiary end points
N otably, hyp erglycem ia has been show n to increase the inclu d ing d ays on m echanical ventilation, renal replace-
risk for nosocom ial and w ou nd infections in su rgical d ia- m ent therap y, length of ICU stay, blood transfu sions, or
betic p atients (34,35). blood stream infections. Severe hyp oglycem ia, d efined as
H yp erglycem ia has been d efined as seru m glu cose con- blood glu cose concentrations of 40 m g/ d L or less, w as
centrations 200 m g/ d L (36), and serum glucose concen- rep orted in 6.8% of p atients in the intensive insu lin grou p
trations of 150 to 200 m g/ d L have been long consid ered as compared w ith 0.5% in the conventional group (p 0.001),
accep table in stressed patients (37). H ow ever, recent d ata w ithou t any rep orted p erm anent sequ elae. Although the
from su rgical intensive care patients show that tighter glu- available resu lts of the N ICE-SUGAR stu d y w ou ld prom p t
cose control m ay be m ore beneficial in red ucing patient the ad op tion of a m od erate target for seru m glu cose con-
morbid ity and m ortality (38). Van d en Berghe et al. concentrations betw een 144 and 180 m g/ d L in critically ill
d u cted a p rosp ective, rand om ized , controlled stu d y to p atients, m ore d ata from su bgrou p analyses m ight provid e
evaluate the outcom es of intensive and conventional an exp lanation of the stu d y find ings and of any d ifferences
insu lin therap y in 1,548 ad u lt surgical ICU p atients. in grou p effects, esp ecially w ith the heterogeneou s popu la-
Patients w ere rand om ized to receive intensive insu lin ther- tion of critically ill p atients (40). Thu s far, low er d egrees of
apy w ith a goal of serum glucose concentrations of 80 to tight glu cose control are now ap p lied to m ost ICU grou p s.
110 m g/ d L or a conventional insu lin therapy to m aintain The Am erican Society for Parenteral and Enteral N u trition
seru m glu cose concentrations betw een 180 and 200 m g/ d L (ASPEN ) and Society for Critical Care Med icine (SCCM)
w hen seru m glu cose levels w ere exceed ing 220 m g/ d L. 2009 Critical Care Gu id elines su ggest a range of serum glu-
Stu d y resu lts show ed that p atients in the intensive insu lin cose concentrations betw een 110 and 150 m g/ d L as appro-
grou p had a 43% red u ction in m ortality, a 46% red u ction in p riate (9).
sep sis, and a 35% red u ction in need for prolonged antibi- In ord er to avoid hyp erglycem ia and allow p hysiologic
otic therap y, as com pared to the conventional insu lin treat- ad ap tation to d extrose infu sion, d extrose infu sion rate in
ment grou p . Patients in the intensive insu lin grou p also ad u lt PN p atients shou ld be started at 2 m g/ kg/ m in as a
continu ou s infu sion. The rate can thereafter be ad vanced ■ Hypoglycemia

to the goal over the next few d ays, based on caloric need s
an d glu cose tolerance to a m axim u m of 4 m g/ kg/ m in . Althou gh su ch sym p tom s of hyp oglycem ia as d iaphoresis,
The d extrose infu sion rate shou ld be kep t at 2 m g/ confu sion, and agitation have been rep orted w hen PN is
kg/ m in in p atients requ iring insu lin u ntil glu cose control abru p tly term inated , hyp oglycem ia is rarely observed in
is achieved. A dextrose infusion rate of approximately 2 mg/ ad u lts; it is m ore com m on in child ren. In a rand om ized
kg/ m in is m ostly su fficient to su p p ress glu coneogenesis controlled stu d y by N iru la et al., 21 ad u lt p atients receiving
for a m axim al bod y p rotein sp aring effect. In obese PN for 24 hou rs w ho w ere started on a clear liqu id d iet
p atien ts (bod y m ass ind ex (BMI), 30) the d extrose infu - w ere rand om ized to abrupt cessation or grad u al tapering
sion rate shou ld be calcu lated based on the ad ju sted id eal of PN . N o significant d ifference in nad ir glu cose levels
bod y w eight since ad ip ose tissu e is not a highly m etabol- w ere seen, and changes in hyp oglycem ic sym p tom assess-
ically active tissu e (41). Caloric d istribu tion in PN is best m ent scores w ere sim ilar (47). H ow ever, a stu d y of child ren
m aintained at 50% to 60% from d extrose, 20% to 30% you nger than 3 years by Bed orf et al. rep orted that 55% (6
from lip id s, an d 10% to 20% from p rotein s. If hyp er- of 11) d evelop ed hyp oglycem ia (seru m glu cose concen-
glycem ia occu rs, a p ortion of the d extrose m ay be su bsti- tration 40 m g/ d L) w ithin 120 m inu tes of abru p t d iscon-
tu ted w ith lip id s u ntil glu cose control is achieved tinu ation of PN (48). It shou ld also be noted that 2 ou t of
w ithou t exceed ing 60% of th e total d aily calories from 10 p atients w hose PN w as grad u ally tap ered off d evel-
lip id s (42). op ed hyp oglycem ia. In ad u lt p atients, grad u al tapering of
If a p atient is receiving PN , 70% of the average slid ing PN ap p ears u nnecessary; how ever, w eaning child ren from
scale insu lin d ose u sed can be ad d ed to the PN solu tion PN shou ld be d one w ith m u ch greater cau tion, and capil-
an d the in su lin d ose can be ad ju sted thereafter. H ow ever, lary blood glu cose levels shou ld be m onitored at least once
the norm al seru m glu cose target betw een 80 and 110 m g/ w ithin 1 or 2 hou rs after PN is d iscontinu ed .
d L p rop osed by the Van d en Berghe et al. stu d y necessi-
tates the u se of an insu lin d rip for the control of severe
hyp erglycem ia (38). Th is allow s titration of th e in su lin
■ Hyperlipidemia
d ose based on seru m glu cose con cen tration s and p ro- H yperlipid emia in patients receiving PN usually manifests
vid es a safe and effective m ethod of glycem ic control, as increased serum triglycerid e levels, although other alter-
althou gh the p ractice of intensive in su lin therap y h as ations in the plasma lipid profile may also occur. H yper-
also been associated w ith in creased in cid en ce of hyp o- triglyceridemia associated w ith PN is mainly the result of
glycem ia (38,43). Su ch tight control of glu cose shou ld be excessive fat synthesis from d extrose overfeed ing, of exces-
confin ed to the ICU setting. Althou gh exogenou s in su lin sive lipid infusion, or of impaired lipid clearance (49). Severe
increases cellu lar glu cose u p take and norm alizes blood hypertriglycerid emia (serum triglycerid e concentrations
glu cose levels, insu lin d oes not increase glu cose oxid a- 1,000 mg/ dL) may precipitate acute pancreatitis (50).
tion. As su ch, little benefit is d erived from excessive d ex- Dextrose overfeed ing (see Table 21.2), not excess lipid
trose infu sion at a rate that exceed s the bod y’s glu cose infu sion, is the m ain cau se of hyp ertriglycerid emia in
oxid ative cap acity. Instead , excess d extrose is converted p atients receiving PN . One-third of glu cose is norm ally
to fat, w hich resu lts in hyp ertriglycerid em ia and fatty converted to fat d u ring lip ogenesis. H ow ever, the am ount
liver (hep atic steatosis). of fat generated can be higher w ith d extrose overfeed ing,
In ord er that they are provid ed w ith ad equ ate calories w ith form ed fat being d ep osited in the liver or transported
and not overfed , critically ill patients shou ld id eally have from the liver as triglycerid e-rich very low -d ensity lip op ro-
their energy expend iture measured using ind irect calorime- teins (VLDLs) (51). In p atients receiving PN , several factors
try on an average of tw o to three tim es w eekly instead of cau se red u ction in lip id em u lsion clearance, inclu d ing
relying on caloric estim ates (44). Data from ind irect calori- sep sis, m u ltiorgan failu re (52), obesity, d iabetes (53), liver
metric m easurem ents shou ld be interpreted in relation to d isease (54), renal failu re (55), p ancreatitis (56), and m ed -
specific p atient factors. Matching caloric intake to energy ications that alter fat m etabolism (e.g., cyclosp orine,
expend itu re is not alw ays possible. In fact, attem pting to sirolim u s, corticosteroid s). Prop ofol, a sed ative agent for-
ad just the carbohyd rate and lipid calories to m atch the m u lated in a 10% lip id em u lsion that is com m only used in
high-energy expend itu re d uring severe hyperm etabolism the ICU, can also cau se a d ose-d ep end ent elevation in
w ou ld likely resu lt in intolerance and m etabolic com p lica- seru m triglycerid e concentrations (57).
tions. In select p atients, heavier sed ation, better p ain con- Intravenou s lip id em u lsions cu rrently m arketed in the
trol, or w ou nd treatm ent m ay be of benefit in red u cing United States are com posed of long-chain triglycerid es
energy exp end itu re. Stu d ies have show n that the use of the (LCTs). LCT-based lip id em u lsions are available in 10%,
-ad renergic blocker prop ranolol in bu rn (45) and head 20%, and 30% em u lsions that p rovid e 1.1, 2, and 3 kcal/
injury (46) p atients m ay attenu ate hyperm etabolism and m L, resp ectively. Follow ing infu sion, the lip op rotein lip ase
possibly red u ce catabolism . This therapy, in an ICU setting, (LPL) enzym e hyd rolyzes lip id p articles in the blood -
may have trem end ou s benefit and im prove ou tcom es in a stream to release fatty acid s. The liver lip ase enzym e
nu m ber of patients. m etabolizes lip id rem nants in the liver to generate VLDLs
and low -d ensity lipop roteins (LDLs). N orm ally, abou t 80% Fatty acid d eficiency is extremely u ncom m on as long as
of lip id s are cleared in 1 hou r. H ow ever, lipid em u lsion som e su p p lem entation of the PN contains lipid s. N ever-
clearance is red uced in critically ill p atients as a result of theless, w ithd raw al of lip id s w ill be m anifested in skin
stress-ind u ced red uction in LPL activity (58). changes, anem ia, throm bocytop enia, and fatty liver.
The d ifferences in the p hosp holip id -to-triglycerid e
(PL/ TG) ratio in the various lipid em u lsion form u lations
are the basis for clearance d ifferences betw een the lip id for-
■ Respiratory decompensation
mu lations. The PL/ TG ratio of the 10% and 20% lip id H yp ercap nia in PN p atients can be the resu lt of excess total
em u lsions is 0.12 and 0.06, resp ectively, and of the 30% calories and carbohyd rate overfeed ing w ith a su bsequ ent
lip id emu lsion 0.06 (30% Liposyn III®) or 0.04 (30% excess p rod u ction of carbon d ioxid e (CO 2). The respiratory
Intralipid ®). An excess of phospholipid s in the 10% em u l- qu otient (RQ VCO 2/ VO 2) for carbohyd rate, protein, and
sion is believed to resu lt in the form ation of abnorm al fat is 1, 0.8, and 0.7, resp ectively, w ith carbohyd rate oxid a-
lip op rotein X p articles. Lip oprotein X is a large p article tion generating the m ost CO 2 p rod u ction. N orm ally,
mad e pred om inantly from phospholipid s and cholesterol energy-m ixed su bstrates yield an RQ arou nd 0.85 (67). An
and has a long half-life of 2 to 4 d ays (59). The lip op rotein X RQ 1 ind icates overfeed ing and lip ogenesis (68). Dex-
particles that ap p ear in the blood of patients w ith the infu - trose infusion rates 4 m g/ kg/ m in in critically-ill p atients
sion of the 10% lipid em u lsions are believed to cau se m ay cau se an increase in RQ that is 1 (69).
hyp erlipid em ia by com peting for m etabolism w ith the The increased respiratory w orkload associated w ith the
infu sed lipid emu lsion particles (60). A 5-d ay infu sion of generation of excess CO 2 p rod u ction m ay exacerbate or
the 10% em u lsion to postoperative traum a p atients resu lt in acu te resp iratory acid osis, resp iratory insu ffi-
resu lted in increased p lasm a p hosp holip id s and choles- ciency, and p rolongation of ventilator d ep end ence (70).
terol levels. Although this w as not observed w ith the infu - These d eleteriou s effects m ay occu r w ithin hou rs of d ex-
sion of the 20% lipid em u lsion (61), others have m ad e su ch trose overfeed ing, esp ecially in cachectic p atients and those
observations (62–64). Althou gh the d ifference has not been w ith lim ited p u lm onary reserves (71). In PN p atients, keep-
show n to alter the clinical cou rse of p atients, higher con- ing d extrose infusion rates 4 m g/ kg/ m in and red ucing
centrations of lip id em u lsions m ay be less d esirable in crit- the total caloric d elivery w ill resu lt in low er CO 2 prod u c-
ically ill su rgical p atients (65). There are concerns abou t the tion (66). Althou gh an RQ 1 may reflect excess carbohy-
possible im m u nosupp ressive effects of the soy-based -6 d rate feed ing, an RQ 1 d oes not exclu d e overfeed ing.
long-chain fatty acid form u lations and their proinflam m a- This is the case for hyp erm etabolic p atients for w hom oxy-
tory characteristics (9). The 30% lipid em ulsion is FDA- gen consum p tion and m inu te ventilation increase w ith
ap p roved for infusion in total nutrient ad m ixtu res (TN A; increased CO 2 p rod u ction (72).
ad m ixtu re of am ino acid s, d extrose, and lipid em u lsions in
one solu tion) and is m ost ad vantageou s in p atients w ith
flu id restriction, d ue to its higher caloric concentration.
■ Refeeding syndrome
In acu tely ill patients receiving PN , seru m triglycerid e Refeed ing synd rom e d escribes the flu id and electrolyte d is-
concentrations shou ld be m onitored at the baseline once tu rbances, vitam in d eficiencies, and glu cose intolerance
the lip id goal is achieved and then once w eekly thereafter. that occur in severely m alnou rished patients u pon rapid
If hyp ertriglycerid em ia occu rs, d extrose overfeed ing initiation of feed ing (oral, enteral, or p arenteral). Metabolic
shou ld be ru led ou t first and the d extrose load shou ld be d erangem ents of the refeed ing synd rom e can resu lt in car-
red u ced if need ed . Red u cing the lipid d ose m ay be neces- d iac, p u lm onary, renal, and neu rom u scu lar com plications
sary if hypertriglycerid em ia d oes not im p rove follow ing that can be reflective of severe electrolyte d ep letion and / or
the red u ction of the d extrose amount. Lipid em u lsions the state of starvation or severe m alnu trition. Patients at
shou ld p referably be infused continuou sly over 24 hou rs to high risk for refeed ing synd rom e inclu d e those w ith
im p rove their clearance (66). chronic starvation, significant w eight loss, chronic alco-
Another possible etiology of hypertriglycerid em ia is holism , anorexia nervosa, w asting d iseases, and malab-
carnitine d eficiency; carnitine is essential for the transport sorp tion synd rom es (73,74).
of fatty acid s into the m itochond ria w here they u nd ergo Hypophosphatemia, hypokalemia, and hypomagne-
oxid ation. This state is particu larly prevalent in p rem atu re semia (see section below) are the three most common and
patients. Daily lip id infusion shou ld be w ithheld w hen the potentially severe electrolyte disturbances that may occur
patient’s seru m is lip em ic or w hen seru m triglycerid e con- d uring the refeeding syndrome. Potassium, magnesium, and
centrations are 400 m g/ d L. In su ch cases, the lip id em u l- organic phosphates are primarily intracellular ions and are
sion d ose shou ld be given only tw o to three tim es w eekly. cofactors in macronutrients metabolism. As a result of signif-
In ord er to p revent essential fatty acid d eficiency, linoleic icant weight loss, the total body stores of these electrolytes
acid shou ld p rovid e 3% to 4% of d aily caloric intake. Prac- become depleted. Serum concentrations may appear normal
tically, p rovid ing 500 m L once w eekly or 250 m L tw ice at first due to their extracellular shift to maintain homeosta-
w eekly of the 20% lipid em u lsion is sufficient to p revent sis. As a result of anabolism and increased insulin secretion in
essential fatty acid d eficiency in ad u lts. response to feeding initiation following starvation, these
electrolytes are red istributed intracellularly, resulting in esp ecially w hen seru m sod iu m levels exceed s 160 m m ol/ L.
decreased serum concentrations (75). With rapid initiation of In this case, the free w ater d eficit is calcu lated and rep laced
carbohydrate feeding, insulin secretion is stimulated and over a 24- to 48-hou r p eriod to p revent com plications
shifts phosphorus and potassium intracellularly. Phosphorus (79,80). Seru m sod iu m levels shou ld be corrected up w ard
demands are also increased for the synthesis of high-energy or d ow nw ard at no faster than 12 m mol/ L. The form u la for
phosphates such as adenosine triphosphate (ATP), 2,3- rep lenishing free w ater is
diphosphoglycerate (2,3-DGP), and glycerol-3-phosphate
dehyd rogenase (G-3PD). With limited phosphorus availabil- Free w ater d eficit (L) 0.6 bod y w eight (kg)
ity in starved patients, the increased phosphorus demand [1 (140/ seru m sod iu m )]
results in severe hypophosphatemia (76,77). A key to pre-
venting the refeed ing syndrome is to first id entify patients at Potassium
highest risk. Once id entified, nutrient delivery, especially of
carbohyd rates, should be started at low amounts and then H ypokalemia can occur w hen there are excess potassium
advanced slowly to the caloric goal over 3 to 5 days. Fre- losses or inad equate intake. Potassium is essential in electri-
quent serum electrolyte monitoring (serum phosphorus, cal cond uction and has a profound effect on muscle func-
potassium, and magnesium initially monitored one to tw o tion, inclu d ing that of card iac m u scles. Severe hypokalem ia
times d aily) w ith ad equate supplementation of phosphate, can cause card iac, neuromuscular, gastrointestinal, m eta-
potassium, and magnesium before and during feeding is bolic, and renal d ysfu nction. H ypokalemia may contribute
usually necessary to replenish electrolyte stores and main- to postoperative ileu s in su rgical patients, and m aintaining
tain normal serum electrolyte levels. Provid ing ad d itional normal serum potassium levels postoperatively is essential
vitamin supplementation to cachectic patients especially to restoring intestinal m otility. As a p atient on PN becom es
w ith thiamine 100 mg/ d ay and folic acid 1 mg/ d ay is rec- anabolic and begins to synthesize new p roteins, an obliga-
ommend ed d uring the first 5 to 7 d ays of initiating nutrition tory requ irem ent exists for intracellular potassiu m utiliza-
support (78). tion. Intravenou s p otassiu m is typ ically ad ministered in
PN at 2 to 4 m Eq/ kg/ d in infants and sm all child ren, and
40 m Eq/ L/ d in old er child ren and ad u lts. H igher potas-
■ Electrolyte abnormalities siu m d oses m ay be required in the early phase of refeed ing;
These issu es occu r m ore comm only w ith PN . Deficiency or the need can be d eterm ined by monitoring the p atient’s
excess of any of the electrolytes m ay happen—the m ost fre- seru m p otassiu m levels. Rep lacem ent m ay be more rapid
qu ent p roblem s are w ith sod ium , potassium , p hosp horu s, w hen central venou s access is available. Continu ou s elec-
and m agnesiu m . trocard iogram (EKG) m onitoring is ad vised w hen higher
d oses are u sed su ch as w hen exceed ing p otassiu m infu sion
Sodium of 20 m Eq/ h in ad u lts. One m ay anticip ate excess potas-
By far the m ost com m on problem encou ntered is hypona- siu m losses w ith em esis and d iarrhea or w hen the patient is
trem ia, typ ically resu lting from the ad m inistration of treated w ith loop and thiazid e d iu retics. In these cases, pro-
hyp otonic solu tions and to a lesser extent from renal or gas- p hylactic potassiu m sup plem entation shou ld be provid ed
trointestinal sod iu m losses. H ypotonic PN solutions and to avoid hyp okalem ia, and seru m p otassiu m levels should
excess free w ater given enterally m ay lead to low er seru m be m onitored m ore frequently.
sod iu m . If seru m sod iu m levels d rop below 120 m m ol/ L, H yp erkalem ia occu rs less frequ ently and m ay be d u e to
neu rologic sym ptom s can occur; it is im perative to correct an error in PN com p ou nd ing. Patients receiving PN m ay
the sod iu m d eficiency over a p eriod of tim e to avoid cen- have an elevated seru m p otassiu m level if they are not sig-
tral pontine m yelinolysis (79). A m inim um d ose of sod iu m nificantly anabolic and are u nable to fu lly u tilize the
is 1 m Eq/ kg/ d , and in general, m ost patients can receive 2 ad m inistered p otassiu m . Other cau ses of hyp erkalem ia
to 3 m Eq/ kg/ d . Preventing hyponatrem ia and other com - inclu d e d ecreased renal fu nction, m etabolic acid osis, tissue
mon electrolyte aberrancies is possible w ith d aily labora- necrosis, and sep sis. Potassiu m intake shou ld be red u ced
tory m onitoring w hen starting PN and ad ju sting nu trient or w ithheld in PN and all other sou rces u ntil hyp erkalem ia
d elivery as need ed . When a stead y state is reached , labora- resolves.
tory param eters can be checked less frequently, three tim es
a w eek, and then w eekly to m onthly in chronic PN Phosphate and Magnesium
patients. In the event of any significant change in the PN Magnesiu m and p hosp hate, as w ell as p otassiu m , are
com position or clinical situations, such as excess em esis requ ired d u ring an anabolic state and d u ring p rotein syn-
and d iarrhea, seru m sod iu m levels should be checked thesis. Phosp hate and m agnesiu m abnorm alities are u su -
more frequ ently. ally noted shortly after initiation of nu tritional su p p ort.
Conversely, hyp ernatrem ia is the result of d ehyd ration This is d u e to a rap id p rod u ction of ATP from d ep leted
d u e to inad equate free w ater intake (either enteral or par- stores, w hich u ses u p the available p hosp hate store and
enteral) or excess w ater losses (em esis, stom a ou tpu t, d iar- shifts it intracellularly (see the section above, titled “Refeed -
rhea, sw eating). Again, neu rologic sym ptom s m ay occu r, ing Synd rome”). It is important to be cognizant of this
phenomenon and check serum phosphorus levels fre- PN can lead to m ore severe liver toxicities, includ ing
quently after starting enteral or PN in a severely malnour- steatosis, steatohep atitis, cholestasis, and cholelithiasis.
ished patient. Severe hypophosphatemia has resulted in H ep atic steatosis d escribes fat accu m u lation in hep ato-
respiratory, neuromuscular, and hematologic complications, cytes w hen liver lipid accu m ulation exceed s its rem oval
and even death in cachectic patients following nutritional (88). Steatohep atitis d escribes an ad vanced stage of severe
initiation without adequate phosphorus supplementation hepatic inflam m ation that can rapid ly progress to liver
(75,81). H ypophosphatem ia can also manifest as paresthesia, fibrosis and cirrhosis (89). Patients w ith hep atic steatosis
w eakness, and convulsions w ithin a few d ays of PN initia- are u su ally asym p tom atic, and liver enzym es correlate
tion (82). Typically, every 1,000 kcal requires about 10 to 15 p oorly w ith the d egree of fatty infiltration (90). Steatosis
mmol of phosphates for ad equate m etabolism. shou ld be ru led ou t w hen hep atom egaly, m alaise, and
Cond itions lead ing to hypokalem ia m ay also cause abd om inal d iscom fort occu r. Althou gh hep atic steatosis in
hyp om agnesem ia (e.g., renal losses and anabolic state), PN p atients is p rim arily the resu lt of d extrose overfeed ing
and su ccessfu l correction of hypokalem ia d epend s on nor- (91), other factors, su ch as lip id overfeed ing (92), and d efi-
malizing seru m magnesiu m levels. H ypom agnesem ia m ay ciencies of carnitine (93), choline (87), and essential fatty
cau se fu nctional ileu s, hyp erreflexia, seizu res, and card iac acid s, m ay also contribu te (94).
and neu rom u scu lar d ysfunction. Typically, an ad u lt PN Excess calories and im balance in the carbohyd rate-to-
form u lation is su pp lem ented w ith 1 to 2 g (8 to 16 m Eq) of lip id ratio in PN can lead to hep atic steatosis (95). Patients
magnesiu m su lfate d aily, in the absence of severe m agne- w ho receive d extrose infu sions have a m u ch greater ten-
siu m losses (renal or intestinal) or d eficiency. d ency (53%) to d evelop hep atic steatosis com p ared to only
17% of those w ho receive a m ixed lip id and d extrose solu -
tion (30% and 70% of nonp rotein calories from lip id s and
■ Acid-base disturbances d extrose, resp ectively) (96). Also, p atients w ho received
Acid -base d isturbances in ad ult patients receiving PN are lip id -free PN d evelop ed fatty liver, p ossibly as a result of
prim arily related to the u nd erlying patient cond itions essential fatty acid d eficiency, and steatosis resolved fol-
rather than to the PN com ponents. H ow ever, excess acetate low in g lip id su p p lem en tation (97). In rare in stan ces
in PN can lead to m etabolic alkalosis (83), and excess chlo- of fat overfeed ing, fat overload synd rom e characterized
rid e can cau se m etabolic acid osis (84). Acid -base d isord ers by hyp ertriglycerid emia, fatty liver, hep atosp lenom egaly,
are m anaged p rim arily by correcting the und erlying p rob- coagu lop athy, fever, and m u ltiorgan d ysfu nction have
lem . H ow ever, altering the chlorid e-to-acetate ratio in PN been d escribed (98).
may be u sefu l in correcting m inor acid -base abnorm alities. Avoid ing carbohyd rate and total calorie overfeed ing
Acetate is converted in vivo at a one-to-one m olar ratio to and p rovid ing balanced PN are essential to p revent hep atic
bicarbonate. As su ch, d iarrhea and enterocu taneou s fistu la steatosis. Up to one-third of total calories can be provid ed
losses resu lting in a bicarbonate d eficit can be ad ju sted by from lip id s, carbohyd rates shou ld p rovid e no m ore than
increasing the acetate sou rces (as sod ium or potassiu m ) in 60% of total calories, and the rem aining calories shou ld
PN . Conversely, in patients w ith high gastric su ctioning, com e from proteins.
increasing the chlorid e salts (su ch as sod ium or potassiu m ) Carnitine d eficiency has been p rop osed as a cau se of
in PN can com pensate for loss of gastric hyd rochloric acid . hep atic steatosis. Carnitine is an am ine that transp orts
LCTs into the m itochond ria for oxid ation and is not a nor-
m al su p p lem ent of PN . Carnitine d eficiency has been p ro-
■ Vitamins and trace elements p osed to cau se liver fat accu m u lation (99). H ow ever,
Vitamin d eficiencies, especially of w ater-soluble vitamins, carnitine d eficiency is p rim arily d escribed in p rem atu re
occur in m alnourished patients. Dextrose infusion increases infants and is extrem ely rare in ad u lts. The role of carni-
thiamine d emand s since thiamine is a cofactor in the inter- tine in enhancing fat clearance and p reventing hep atic
med iate carbohyd rate metabolism. Thiamine d eficiency has steatosis rem ains qu estionable. The correlation betw een
resulted in Wernicke encephalopathy (85) and lactic acid osis p lasm a and tissu e carnitine levels is u ncertain; p atients
(86). PN supplementation w ith at least the five trace ele- m ay have norm al p lasm a carnitine levels and still d evelop
ments (zinc, selenium, copper, manganese, chrom ium) is hyp ertriglycerid em ia.
critical, as a number of trace element d eficiencies may occur The role of choline d eficiency in hep atic steatosis is also
especially in PN -dependent patients w ith intestinal fluid u nclear. Choline is a qu aternary am ine that is ubiquitous in
losses (zinc and selenium lost in d iarrhea, enterocutaneous d iet. It is also d erived in vivo from m ethionine m etabolism.
fistulas, short bow el synd rome; see Tables 21.3 and 21.4). Deficiency of p hosp hatid ylcholine, a byp rod u ct of choline
and a comp onent of lip op rotein synthesis, has been pro-
p osed to cau se abnorm al lip op rotein p rod u ction and to
■ Liver complications p rom ote triglycerid e accu m u lation in the liver (100).
A transient elevation of liver enzymes is com m on w ithin 1 Althou gh m ethionine is p rovid ed from am ino acid s in PN ,
to 2 w eeks of PN initiation, but liver enzym es w ill retu rn to choline d eficiency m ay still occur as intravenou s m ethion-
norm al follow ing PN cessation (87). H ow ever, p rolonged ine is m etabolized d ifferently than it is w ith enteral
Table 2 1 .3 Req u ir em en t s a n d clin ica l ch a r a ct er ist ics of som e gen era lly r ecogn ized m icron u t r ien t s
Adult Dietary Reference Daily Maintenance
Intakes (DRIs) and Adult Dose for Oral Requirements for
Recommended Dietary Supplementation to Parenteral
Nutrient Allowances (RDAs)a Signs of Deficiency Laboratory Assay Treat Deficiency Supplementation
Iron 8–18 mg/d (DRIs) Pallor, fatigue, Iron/TIBC ratio, 2–3 mg/kg/d elemental 1–1.2 mg
microcytic anemia ferritin iron, in 2 to 3 divided
doses
Iodine 150 g/day (RDAs) Goiter, hypothyroidism Urine iodine 150–300 g potassium 100 g
iodide 400 g
(di-iodotyrosine for
endemic goiter)
Zinc 8–11 mg/d (RDAs) Acrodermatitis Serum and urine 2.5–15 mg/d elemental 2.5–5 mg
enteropathica, growth zinc zinc
retardation, hair loss,
delayed wound healing
Copper 900 g/d (RDAs) Hypochromic anemia Serum copper, 2–3 mg/d elemental 0.3–0.5 mg
not responsive to iron, ceruloplasmin copper (cupric sulfate)
neutropenia, steely hair
Manganese 1.8–2.3 mg/d (DRIs) Scaly dermatitis, Urinary N-methyl 2–5 mg/d elemental 0.2–0.3 mg
retarded hair and nail nicotinamide manganese
growth, increased
prothrombin time (PT)
not responsive to
vitamin K, hypercalcemia,
hyperphosphatemia
Chromium 20–35 g/d (DRIs) Neuropathy, high free Glucose tolerance 200 g/d 10–15 g
fatty acids, glucose test
intolerance not
responsive to insulin
Selenium 55 g/d (DRIs) Cardiomyopathy, Serum selenium, 70 g/d 20–60 g
muscle pain, weakness, glutathione
macrocytosis, skin and peroxidase activity
hair depigmentation,
glucose intolerance
a
Based on the Food and Nutrition Board, Institute of Medicine—National Academy of Sciences, DRIs are reference values that are quantitative estimates of nutrient intakes to
be used for planning and assessing diets of healthy people. RDAs are set to meet the needs of almost all (97%–98%) individuals in a group. From Btaiche IF, Khalidi N,
Kovacevich DS, eds. The parenteral and enteral nutrition manual, 8th ed. Ann Arbor, MI: The University of Michigan Hospitals and Health Centers; 2009.
Food and Nutrition Board, Institute of Medicine-National Academy of Sciences: www.iom.edu.
Daily Requirements for Parenteral Supplementation from ESPEN Guidelines on Parenteral Nutrition: Surgery.
Table 2 1 .4 Vit a m in d efi cien cies/t oxicit ies w it h clin ica l ch a ra ct er ist ics
Vitamin Deficiency Toxicity
A Dry skin, hyperkeratosis, dry conjunctiva Hepatomegaly, muscle pain, malaise, ophthalmoplegia,
fever, icterus, rash, pseudotumor cerebri
B1 (thiamine) Beriberi, encephalopathy, heart failure, confusion, decreased tendon None
reflexes, acidosis
B2 (riboflavin) Angular stomatitis, cheilosis, atrophy of lingual papillae, glossitis, Photohemolysis in premature infants
magenta tongue
B6 (pyridoxine) Personality changes, irritability, depression, filiform hypertrophy of lingual Sensory neuropathy, degeneration of sensory root
papillae, aphthous stomatitis, nasolabial seborrhea, forehead rash Ganglia
B12 Megaloblastic anemia, neurologic symptoms, sore tongue, None
weakness, neuropsychiatric manifestations
K Elevated prothrombin time None
ad m inistration (101). Lim ited d ata are available abou t the PN AC is reversible if PN is d iscontinued before irre-
effects of choline su pplem entation on reversing steatosis in versible liver d am age occu rs. Becau se of the d etrim ental
PN p atients (102). A pilot stud y of hom e PN patients w ith effects of bow el rest, early initiation of enteral or oral feed -
hep atic steatosis show ed that intravenous choline chlorid e ings and w eaning PN is the best w ay to p revent PN AC. In
sup p lem entation at 2 g/ d ay in PN for up to 24 w eeks w as ad d ition, it is essential to avoid overfeed ing, u se balanced
safe and effective in red u cing the d egree of hep atic steato- sou rces of calories, cycle PN , and avoid and p rom ptly treat
sis (103). More research, how ever, is need ed to clarify the sep sis.
role of choline in liver d isease and before rou tine choline Pharm acologic m easures have been used to p revent
su p p lem entation to PN can be recom m end ed . PN AC, im p rove bile flow, p rovid e sym p tom atic relief of
PN -associated cholelithiasis is the result of d ecreased cholestasis, and red u ce the toxic insu lts to the liver. Unfor-
gallblad d er contractility d uring fasting. In the absence of tu nately, there is little evid ence show ing d efinitive efficacy.
oral intake or enteral stimulation, there is d ecreased secre- Ursod eoxycholic acid has been show n to im prove bile flow
tion of cholecystokinin (CCK), a peptid e hormone secreted and red u ce the clinical signs and sym p tom s of cholestasis;
by the duodenum in response to meals to induce gallbladder how ever, a p rosp ective stu d y in infants (the grou p m ost
contractility (104). Fasting PN patients have been observed p rone to PN AC) failed to d emonstrate d ru g efficacy (127).
to have a d istend ed gallblad d er and absence of gallblad d er Cholecystokinin-octapeptid e (sincalid e) w as u sed in
contractions, a find ing not observed in enterally fed patients infants to ind uce gallblad d er contraction and im p rove bile
(105). As a result of bile stasis, bile accumulation in the bil- flow (128). In a recently p erform ed controlled trial, how -
iary tract facilitates cholesterol gallstone formation (106) and ever, u se of cholecystokinin w as not show n to be effective
calcium bilirubinate precipitation in the form of slud ge in p reventing PN AC (129). Treatm ent of bacterial over-
(107). Biliary slud ge, gallstones, and hyperviscous and tena- grow th w ith oral antibiotics (e.g., m etronid azole, gentam -
cious bile w ere recovered d uring gallblad d er surgery to icin, neom ycin) d u ring p rolonged bow el rest may be
relieve refractory cholestasis in PN -dependent patients beneficial in red u cing bacterial translocation across the
(108,109). Patients w ith short bow el synd rome are especially intestinal w all and p ossibly p revent their p otential hepato-
at increased risk for cholelithiasis and biliary sludge (110). toxic effects (130).
This is d ue to impaired bile flow, disrupted bile enterohep- The lip id com p osition w ithin total PN (TPN ) has been
atic cycling, and canalicular accumulation of toxic bile acids, garnering m ore attention as a potential contribu ting factor
such as lithocholic acid (111). Although use of cholecys- to the d evelop m ent of PN associated liver d isease
tokinin-octapeptid e has been suggested in patients receiving (PN ALD). Trad itional lip id em u lsions contain m ainly
a prolonged course of PN, results have been mixed at best om ega-6 p olyu nsatu rated fatty acid s (som etim es referred
(112,113), and a recent stud y has failed to show efficacy in to as n-6 PUFA) d erived from soy or safflow er oils. These n-
preventing cholelithiasis in neonates (114). 6 PUFAs have been associated w ith p roinflam m atory activ-
PN-associated cholestasis (PN AC) occurs primarily in ity (3,23,131). Som e researchers have su ggested that the
infancy and is less com m on in old er child ren and ad u lts accu m u lation of n-6 PUFA as w ell as other p rod ucts found
(115,116). Factors pred isposing to PN AC includ e d u ration in com mercial p rod u cts, inclu d ing p hytosterols, contribute
of PN , prematurity, overfeed ing, short bow el, bow el rest, to the d evelop m ent of PN AC (4,132). The u se of alternative
and sep sis (117,118). More recently, PN AC has been fatty acid s, su ch as m ed iu m chain triglycerid es, olive oil, or
d escribed in a number of ad ult patients on long-term PN om ega-3 fatty acid s have been p rop osed as p otential m eth-
(119). The etiology of PNAC is unknow n. Bow el rest lead s od s for treatm ent of PN ALD. Three sm all case series report
to increased intestinal permeability, alteration in gut hor- a d ram atic im p rovem ent in PN ALD in p atients treated
mone secretion, red uction in bile flow, d ecreased bile salt w ith om ega-3 fish oil based lip id s (6–8). In ad d ition to these
excretion, bacterial overgrow th, bacterial and end otoxin effects, several stu d ies com p aring fish oil su pplem ented
translocation from the gut, and impaired intestinal TPN to stand ard soy-based TPN , fou nd shorter postopera-
immu nologic mechanisms (120,121). All these factors may tive hosp ital stay (10), d ecreased severe infectious com pli-
contribute to the d evelopment of PN AC. Most recently, a cations (10), and d ecreased m ortality (11) associated w ith
d erangement in the expression of bile canalicular transport the form er. A larger stu d y show ed a trend tow ard s
proteins has been show n in a rod ent mod el of PN (122–124). d ecreased hosp ital length of stay in the fish oil grou p , bu t
These transport proteins are responsible for the prod uction this d id not reach statistical significance (12).
of bile w ithin the canalicular space, and a loss of this func- Olive oil or m ed iu m chain triglycerid e-based lip id for-
tion may w ell be a major mechanism in the d evelopment of m u lations have also been exam ined in smaller, short-term
PN AC. Liver function tests in patients w ith PN AC may clinical trials. While resu lts ind icate that these form ulations
show increased serum liver transaminases, alkaline phos- are safe to ad m inister, there are conflicting find ings as to
phatase, biliru bin, and gamma glutamyl transferase con- w hether there is a real clinical benefit in term s of red u ced
centrations (125). H ow ever, a rise in serum conjugated infectiou s com p lication rate or shorter hosp ital stay. At this
biliru bin concentration 2 mg/ d L is consid ered the m ost p oint, more research is need ed to clarify the m echanism of
commonly accepted marker of cholestasis. Jaund ice occurs action of these variou s lip id form u lations and their clinical
w ith ad vanced cholestasis (126). effects.
Short bow el synd rom e p atients w ith end -stage liver cations. Malpositioning occurs frequently w ith subclavian
d isease m ay benefit from com bined liver and bow el trans- access w ith the catheter tip ending in the ipsilateral jugular
plantation. Early referral of short bow el synd rom e p atients vein or the contralateral innominate. Therefore, it is manda-
at high risk for liver com p lications for bow el transplanta- tory to check the catheter position rad iographically before
tion m ay possibly becom e a viable life-saving option before usage—either with fluoroscopy or static images. Pneumoth-
irreversible liver d am age occurs (133). orax occurs in 1% to 2% of cases of central venous catheter
insertion; this usually occurs w hen obtaining subclavian
access and less commonly with the internal jugular vein.
■ COMPLICATIONS OF NUTRITION
This is d ue to transgression of the pleural space and punc-
SUPPORT DELIVERY ture of lung apex (136). Another complication of malposi-
Delivery system s d ep end on the rou te of nu tritional tioning is the pinch-off synd rome (137,138). In this
sup port—p arenteral or enteral. In ad d ition, there are a lim - cond ition, a catheter placed into the subclavian vein is
ited nu m ber of broad categories of these d elivery p rob- pinched between the first rib and clavicle d ue to it being
lem s, inclu d ing m echanical, infectious, and throm botic inserted too medially. It may manifest itself as catheter occlu-
com plications for the intravenous route, and m echanical sion d epend ing on bod y position or as the inability to aspi-
and infectiou s for the enteral rou te (Tables 21.5 and 21.6). rate blood . If clinically suspected , it should be confirmed by
chest rad iography and removed w ith insertion of a more lat-
erally placed device. Failure to replace such a line may lead
■ Parenteral nutrition to catheter d isruption and embolus of the d istal end . The
Mechanical d etails of proper central venous access insertion are beyond
the scope of this section, but Table 21.5 contains a list of the
Although PN can be delivered via the peripheral route, it has
potential complications.
several lim itations, includ ing osmolarity-ind uced throm bo-
sis and phlebitis, w hich limits the concentration of d extrose Infectious
to 10% in ad olescents and ad ults and 12.5% in infants and
Infectiou s com plication rates associated w ith PN range
small child ren, thus limiting the total number of calories via
from 7% to 27% (139). If p rop er sterile and aseptic tech-
this route. PN via central vein infusion is thus preferred .
niqu es are not u sed w hile obtaining central venou s access,
Central venous access is usually obtained via a percutaneous
acu te catheter infections can occu r. It is vital to perform
route to the internal jugular or subclavian or the common
p lacem ent w ith gow n, gloves, and m ask. This is especially
femoral veins. More commonly, access may be obtained by
true w hen perform ing tu nneled catheter access for pro-
peripherally inserted central catheters (PICC) (134). Needle
longed nu tritional su p p ort. Care m u st be taken w hen
injury to the vein or an adjacent artery is rare but does occur,
accessing these catheters as w ell. Use of central venou s
especially in unskilled hands (135). Malposition of the
catheters (CVC) for m u ltip le d ru gs and blood d raw s, as
catheter can lead to problems as w ell. This includ es card iac
w ell as PN , has been show n to increase infectiou s com pli-
injury, pericardial effusion and tamponade, and arrhyth-
cations (140,141). In fact, w hen a formal p rotocol for
mias. Ad d itionally, if the catheter is not located centrally,
catheter insertion and care is institu ted , a d ram atic red u c-
these hypertonic solutions can result in thrombotic compli-
tion in catheter infections can be seen. In one p rospective
stu d y, the rate of catheter infections d eclined from
11.3/ 1,000 catheter d ays to 1.6/ 1,000 catheter d ays over the
Table 2 1 .5 Pot en t ia l com p lica t ion s of cen t ra l 4-year p eriod in w hich these m ethod s w ere u sed (142). It
ven ou s a ccess ap p ears that m u ltip le central venou s lu m ens m ay pred is-
p ose p atients to a higher risk of infection, bu t this associa-
Pneumothorax
tion is not p roven (143). PICCs d id not have a significantly
Hemothorax low er incid ence of infection; how ever, PICCs have been
Subclavian artery/vein injury associated w ith higher rates of throm bop hlebitis (144).
Cardiac injury/arrhythmias Catheter infections may occur from one of three sources:
the insertion site, the hub, or seeded via the bloodstream.
Carotid artery injury
The hub has often been considered the most common source
Catheter malposition of CVC infections, and great care must be used to protect this
Catheter embolism site w hen gaining access to these catheters (145). Infections
Thromboembolism secondary to bacteria from around the entrance site includ e
skin contaminants such as staphylococci or streptococci
Thoracic duct injury
(146). These organisms can colonize the fibrin sleeve that
Lung injury d evelops around the catheter tip and start proliferating.
Nerve injury Other infections are a result of seed ing from other foci, such
Air embolism as bacterial translocation, and may be Gram-negative or
enteric in nature (147). One of the m ost common sources of
Table 2 1 .6 Pot en t ia l com p lica t ion s of en t er a l feed in g a n d p r even t ive in t er ven t ion s
Complication Possible Reasons Suggested Treatment
Gastrointestinal
Diarrhea (6–8 loose, Osmotic overload • Review medications for hypertonic elixirs, sorbitol-containing oral liquid medications,
watery stools per day) and antacids
• Dilute elixirs and change to nonsorbitol-containing oral liquid medications
• Provide continuous feeding rather than bolus
• May require judicious use of antidiarrheal medication
Lactose intolerance • Change formula to lactose-free
• Monitor lactose intake if also taking oral diet
Contaminated formula • Change bag and tubing every 24 hours
Nervous tension • Promote restful environment
Bacterial overgrowth; oral medications • Review oral medications, especially for antibiotics and H2 receptor antagonists for
possible side effects
Intestinal infection • Rule out and treat Clostridium difficile infection
Low residue feedings • Use of fiber-enriched formula may be helpful
Nausea Volume overload • Decrease total volume/flow rate
Vomiting Obstruction, delayed gastric emptying, • Rule out obstruction
drug-induced • Evaluate medication profile
Cramping Intolerance due to rapid administration • Decrease total volume/flow rate
Delayed gastric emptying Diabetes, gastric surgery, trauma, sepsis • Check gastric residuals every 4 hours and return up to 200 mLinto the stomach
• If residuals 200 mL, hold tube feeding for 1 hour and recheck
• May also consider small bowel feeding
Constipation Insufficient fluid intake • Increase fluid intake
Decreased bowel mobility • Increase physical activity as tolerated
Low residue feedings • Use of fiber-enriched formula may be helpful
Metabolic
Altered glucose, electrolyte, Excess or insufficient administration; • Monitor glucose, especially in diabetics and in elderly
LFTs, and renal function tests prolonged administration of tube feeding • Sudden glucose intolerance may indicate sepsis
containing low sodium; excessive free • Measure electrolytes and input and outputs
water • Weigh regularly
• Reassess appropriateness of feeding formula
• Reduce free water requirements
Dehydration Insufficient free water • Increase fluid intake
• Administer additional free water each day based on body weight
• Monitor input and output
Diarrhea • See gastrointestinal complications
Hyperglycemia • Monitor glucose, especially in elderly and diabetic patients
Overhydration Excess fluid administration; renal failure • Decrease volume of fluid administered
• Monitor input and output
• Reassess appropriateness of feeding formula; switch to a calorie dense formula
Mechanical
Dislodged tube Confused patient • Restrain patient, bridle tube, place decoy tube, or place permanent feeding tube
Obstructed tube Inadequate flushing • Flush tubes with 5–30 mLevery 4 hours, after checking gastric residuals, medication
administration, and stopping feeding
Incompatible medications • Administer medication individually; do not add medications to feeding bag
Tablets • Crush medications well or use liquid forms
• Have patient take tablet orally, if possible
• Suggested treatment: instill in tube a mixture of one crushed tablet of Viokase® with
one crushed tablet of sodium bicarbonate dissolved in 5 mLof warm water; clamp tube
for 5–10 minutes, then gently flush tube
Aspiration Rapid administration of feeding • Decrease administration flow rate
• Check gastric residuals every 4 hours
• Hold tube feeding if gastric residual volume 200 mLon two successive checks, hold
feeding for 1 hour and recheck residuals
Incorrect patient position • Raise head of bed at least 30 to 45 degree during continuous feeding and 1 hour
after and during bolus feedings
Tube malposition • Confirm placement with low upright chest x-ray
• Be aware that a feeding tube can come into the pharynx with coughing or other
activity; if in doubt, check by aspiration, insufflation, or x-ray
From Btaiche IF, Khalidi N, Kovacevich DS, eds. The parenteral and enteral nutrition manual, 9th ed. Ann Arbor, MI: The University of Michigan Hospitals and Health Centers; 2009.
CVC infections is the hub itself. In one stud y, the majority of that this ap p roach can also be u sed to p revent the d evelop -
CVC infections w ere d ue to an infected hub, w ith negative m ent of su ch infections (159).
skin cultures (145). Although tunneling of the catheter w as
initially thought to reduce the rate of CVC infections, this Thrombotic
does not appear to reduce infection rates (148). Chronic ind w elling central catheters are associated w ith
Fu ngal infections are d read ed p roblem s, as they are d evelop m ent of throm bi. These m ay p resent acu tely w ith
associated w ith higher m ortality, esp ecially in im m u no- ip silateral lim b sw elling and inability to infu se solu tions.
com p rom ised ad u lts (149). In general, a p ositive fu ngal Fortu nately, they rarely lead to a p u lm onary em bolism .
cu ltu re w ill requ ire catheter rem oval as they are otherw ise Treatm ent by catheter rem oval and replacem ent in an alter-
recalcitrant to therap y (150). Attem p ts to clear a fu ngal nate site is u su ally su fficient. Unfortu nately, in patients
infection are only occasionally su ccessfu l and often resu lt w ith long-term d ep end ence on PN , this m ay lead to loss of
in d eath. For m ost bacterial infections, if the p atient is clin- access sites and , w ith no access, loss of nu trition. Som e
ically not in sep tic shock, treating throu gh the catheter ad vocate the u se of anticoagu lation therap y in low d oses
w ith antibiotics is ap p rop riate (151,152). This ap p lies to (e.g., w arfarin or u rokinase) to p revent these com plica-
silastic catheters; tem p orary p olyvinyl chlorid e lines, how - tions, w ith som e su ccess (160,161); how ever, there is no
ever, m u st be rem oved . In general, bacterial infections w ill evid ence to su p p ort the rou tine u se of anticoagu lation to
clear from a silastic catheter 80% to 90% after the first prevent CVC-associated venous thrombosis (5). The catheter
infection and less frequ ently w ith su bsequ ent infections itself may also become occluded due to thrombosis. Such
(153). Lack of clearance requ ires rem oval of the catheter. problems may be treated with intracatheter lytic therapy.
Treatm ent failu re is m u ch m ore frequ ently seen in the Catheters that have been in place for longer periods of time
p resence of abscess, im m u nocom p rom ised statu s, and the may also suffer occlusion from calcium deposits or lipid
organism s Pseudomonas aeruginosa and Candida albicans. d eposits, w hich may respond to dilute infusion of hydrochlo-
Data from a series of p ed iatric p atients w ith short bow el ric acid or ethanol (162).
synd rom e su ggest that these p op u lations are at highest
risk for catheter infections (154,155). Patients w ho m ani-
fest w ith a catheter infection along the su bcu taneou s track
■ Enteral nutrition
requ ire catheter rem oval, as antibiotics are generally inef- Like p arenteral ad m inistration, enteral d elivery of nu tri-
fective in these cases. tion is associated w ith a w id e num ber of com plications
The usual w orkup of a patient on PN who develops an (Table 21.6).
acute, unexplained fever should includ e a blood culture. The
clinical practice guid elines for the d iagnosis and manage- Mechanical
ment of intravascular catheter-related infection by the Infec- Enteral nu tritional su p p ort is u su ally obtained by som e
tious Diseases Society of America recommend that paired form of access to the gastrointestinal tract. For relatively
blood samples are draw n from the suspected catheter and a short-term su p p ort, tem p orary tu bes via the nose or m outh
peripheral vein for culture. If a blood sample cannot be are u sed . These tu bes can irritate and d am age the m ucosa
draw n from a peripheral vein, then two blood samples of the nasal p assage, cau sing rhinorrhea, ep istaxis, and a
should be d raw n from d ifferent catheter lumens. A d efini- blockage of the sinu ses, lead ing to sinu sitis. A w ell-
tive d iagnosis of catheter-related blood stream infection d escribed sou rce of fevers of u nknow n origin in a p atient
(CRBSI) should be based on the find ing of the same organ- w ith a long-stand ing nasoenteric tu be is m axillary sinu si-
ism that grow s from at least one percutaneous blood culture tis. This is best treated by rem oval of the tu be, nasal d econ-
and from a catheter tip culture; alternatively, two blood sam- gestant sp rays, and occasional d rainage of the sinus.
ples should be draw n one from the catheter hub and from a Occasionally, if the feed ing tu be is not secu red appropri-
peripheral vein, so that, when cultured, they meet the CRBSI ately, the cartilage of the anterior nares m ay be d am aged .
criteria for quantitative blood cultures or d ifferential time to Inflam m ation arou nd the eu stachian tubes in the nasophar-
positivity (156). Empiric antibiotic therapy may be used if ynx m ay lead to otitis m ed ia. To avoid these p roblem s, the
the patient appears septic. Most fevers are d ue to some other new er enteral feed ing tu bes are sm aller and less rigid ;
source; how ever, if fever persists, a catheter change over a how ever, these sm aller tu bes m ay carry an increased risk of
w ire (for temporary lines) w ith a quantitative or semiquanti- being p ositioned in the tracheobronchial tree, esp ecially in
tative culture of the catheter tip should be perform ed . an obtu nd ed or sed ated p atient (163). To id entify this prob-
New er catheters that are impregnated w ith antibiotics may lem before d am age occu rs, it is necessary to obtain rad io-
reduce the incidence of infections (157). logic confirm ation of the tu be p osition p rior to initiating
Recent d ata have show n tremend ous benefit in preven- feed s. Au scu ltatory confirm ation alone, thou gh a help ful
tion of central venou s line infections w ith the u se of ethanol ad ju nct, is not ad equ ate.
lock therap y (158). A retrospective stu d y show ed that u se In certain p atients w ith gastric em p tying p roblem s or
of a 70% ethanol lock therap y w as able to both treat over reflu x, p ostp yloric tu bes are u sed . These are p laced via the
80% of central venou s line infections in a ped iatric hem a- nares and have w eighted tip s that allow them to be carried
tology oncology setting. A m ore recent paper has show n p ast the p ylorus into the d u od enum w ith p eristaltic action
(164). These tu bes m u st be marked after confirm ing p lace- As m entioned p reviou sly, sinu sitis and otitis m ed ia can
ment as they m ay be d islod ged . Occasional com p lications occu r in p atients w ith nasal tu bes. Sinu sitis is m ore com -
noted w ith these tubes have been d am age to the esophagus m on and is seen alm ost u niversally w ith these tu bes. It m ay
or stom ach w ith gastritis and perforations. These occu r p resent as u nexp lained fevers in p atients or w ith nasal d is-
more often w ith the m ore rigid tubes. Acu te gastric d isten- charge. Using sm aller caliber tu bes has d ecreased bu t not
tion m ay also occur, especially in patients receiving naso- eliminated this p roblem . A com p u terized tom ography (CT)
gastric bolu s feed ing or w ith gastroparesis. This can lead to scan of the head is frequ ently u sed to m ake this d iagnosis.
vom iting and asp iration (see the next section) as w ell as Treatm ent consists of m oving the tu be to the other sid e and
perforation of the stom ach. Ad d itionally, acute d istention em p loying nasal sp rays and antibiotics. If longer term
of the stom ach m ay cau se hyp otension from a vagal nu tritional su p p ort is d eem ed necessary, consid eration
resp onse. To avoid this, the stom ach should be asp irated shou ld be given to su rgical access.
period ically to ensu re that it is em ptying. Occasionally,
med ications m ay be requ ired to enhance gastric m otility or
a change to a p ostpyloric tu be m ay be called for. ■ SUMMARY
Long-term enteral access is u su ally obtained su rgically. Ad vances in nu tritional science over the last fou r d ecad es
Access can be either to the stom ach or to the jejunu m , have im p roved the care of cou ntless p atients. The m an-
d ep end ing on the patient’s specific need s. Technical com - agem ent of nu trition can have com p lications, how ever, in
plications from the operation m ay occur. These tu bes m ay the p rovision of too m u ch or too little of any nu trient or
also be m alp ositioned and d islod ged , requiring rep lace- su p p lem ent, as w ell as m echanical or infectiou s com p lica-
ment. In the p ast 20 years most enteral feed ing tu bes have tions of the d elivery m echanism . Know led ge of these
been p laced u sing m inim ally invasive techniqu es [p ercu ta- com p lications is critical to p rop er p lanning and p atient
neous end oscopic gastrostom y (PEG) or laparoscopic] m anagem ent.
(165,166). Early d islod gem ent of a PEG m ay cau se the
stom ach to p u ll aw ay from the abd ominal w all and lead to
peritonitis (165). After 3 m onths the stom ach is generally ■ REFERENCES
w ell ad hered to the abd om inal w all. When these tu bes 1. Ku d sk K, Croce M, Favian T, et al. Enteral versu s p arenteral feed ing.
becom e d islod ged , especially in child ren, the access hole Effects on sep tic m orbid ity after blu nt and p enetrating abd om inal
shrinks fairly rap id ly, often w ithin a few hou rs. The care- trau m a. Ann Surg 1992;215(5):503–511.
2. Bu zby G. Periop erative total p arenteral nu trition in su rgical p atients.
givers and patients m u st be instructed to take im m ed iate The Veterans Affairs Total Parenteral N u trition Coop erative Stu d y
action to rep lace the tu be if this occu rs. Grou p . N Engl J Med 1991;325(8):525–532.
3. Klein S, Kinney J, Jeejeebhoy K, et al. N u trition su p p ort in clinical
Infectious p ractice: review of p u blished d ata and recom m end ations for fu tu re
research d irections. JPEN J Parenter Enteral Nutr 1997;21:133–156.
Aspiration is the m ost feared com plication from enteral 4. H eyland DK, MacDonald S, Keefe L, et al. Total parenteral nu trition in
nu trition (167). This can result from either a p rim ary tu be the critically ill p atient: a m eta-analysis. JAMA 1998;280(23):2013–2019.
5. Braga M, Lju ngqvist O, Soeters P, et al. ESPEN gu id elines on p ar-
malposition in the tracheobronchial tree or from reflux/ enteral nu trition: su rgery. Clin Nutr 2009;28(4):378–386.
emesis. Aspiration of stomach contents may be particu larly 6. Minard G, Kud sk KA. Postop erative nu trition in su rgery for m ajor
harm ful as the acid lead s to severe pneu m onitis and a cap il- trau m a. Curr Opin Clin Nutr Metab Care 1998;1(1):35–39.
7. Bou langer BR, Brennem ann FD, Rizoli SB, et al. Insertion of a transp y-
lary leak into the alveoli, causing the ad ult respiratory d is- loric feed ing tube d u ring laparotom y in the critically inju red : ration-
tress synd rome (ARDS). Although enteral feed ings are ale and p lea for rou tine u se. Injury 1995;26(3):177–180.
clearly less expensive than PN , complications in the tw o 8. August D, Teitelbau m DH . Gu id elines for the u se of p arenteral and
enteral nu trition in ad u lt and p ed iatric Patients. JPEN J Parenter
grou ps are not d issimilar. In a recent m eta-analysis examin- Enteral Nutr 2002;26(1):1SA–137SA.
ing com plications by these tw o routes, complication rates 9. McClave SA, Martind ale RG, Vanek VW. Gu id elines for the p rovision
w ere the same in both groups (24). Although postp yloric and assessm ent of nu trition sup port therap y in the ad ult critically ill
p atient: Society of Critical Care Med icine (SCCM) and Am erican Soci-
feed ings have been ad vocated in the early postoperative ety for Parenteral and Enteral N u trition (ASPEN ). JPEN J Parenter
period (7), this may not have as great an ad vantage as ini- Enteral Nutr 2009;33:277–316.
tially perceived . In fact, the incid ence of aspiration d oes not 10. Mu llen JL, Bu zby GP, Wald m an MT. Pred iction of op erative m orbid -
ity and m ortality by p reop erative nu tritional assessm ent. Surg Forum
significantly d iffer for patients in relation to w hether they 1979;30:80.
are receiving postgastric or intragastric feed ings (168,169). 11. Cam eron JW, Rosenthal A, Olson AD. Malnu trition in hosp italized
In cases w here gastric acid secretion has been controlled child ren w ith congenital heart d isease. Arch Pediatr Adolesc Med 1995;
149(10):1098–1102.
w ith histamine receptor blocking d rugs or proton pump 12. Merritt RJ, Blackbu rn GL. N u tritional assessm ent and m etabolic
inhibitors, the stom ach contents becom e colonized w ith resp onse to illness of the hosp italized child . In: Su skind RM, ed . Text-
Gram-negative bacteria; aspiration of this w ould poten- book of Pediatric Nutrition. N ew York: Raven Press; 1981:285–307.
13. Baker J, Detsky A, Wesson D. N u tritional assessm ent: A com p arison
tially lead to a bacterial pneumonia. These complications of clinical jud gem ent and objective m easu rem ents. N Engl J Med 1982;
significantly p rolong hospital and intensive care stays, may 306:969–972.
lead to m ortality, and certainly lead to increased health care 14. Ingenbleek Y, You ng VR. Significance of transthyretin in p rotein
m etabolism . Clin Chem Lab Med 2002;40:1281–1291.
costs. Thus, taking precautions to avoid them should be 15. Detsky JM, Baker JP, O’Rou rke K, et al. Periop erative p arenteral nu tri-
part of rou tine and protocol d riven care. tion: A m eta-analysis. Ann Intern Med 1987;107:195–203.
16. Bistrian BR. N utritional assessm ent and therap y of p rotein–calorie 44. H u nter DC, Jaksic T, Lew is D, et al. Resting energy exp end itu re in the
m alnu trition in the hosp ital. J Am Diet Assoc 1977;71(4):393–397. critically ill: estim ations versu s m easu rem ents. Br J Surg 1988;75(9):
17. Bistrian BR. Interaction of nu trition and infection in the hosp ital set- 875–878.
ting. Am J Clin Nutr 1977;30(8):1228–1235. 45. H ernd on DN , H art DW, Wolf SE, et al. Reversal of catabolism by beta-
18. Keenan RA, Mold aw er LL, Yang RD, et al. An altered resp onse by blockad e after severe bu rns. N Engl J Med 2001;345:1223–1229.
perip heral leu kocytes to synthesize or release leu kocyte end ogenou s 46. Chiolero RL, Breitenstein E, Thorin D, et al. Effects of p rop ranolol on
m ed iator in critically ill, p rotein-m alnou rished p atients. J Lab Clin resting m etabolic rate after severe head inju ry. Crit Care Med 1989;17:
Med 1982;100(6):844–857. 328–334.
19. Reynold s JV, O’Farrelly C, Feighery C, et al. Im p aired gu t barrier 47. N irula R, Yam ad a K, Waxm an K. The effect of abru p t cessation of total
fu nction in m alnou rished p atients. Br J Surg 1996;83(9):1288–1291. parenteral nutrition on seru m glu cose: a rand om ized trial. Am Surg
20. Wiren M, Sod erholm JD, Lind gren J, et al. Effects of starvation and 2000;66(9):866–869.
bow el resection on p aracellu lar p erm eability in rat sm all-bow el 48. Bend orf K, Friesen CA, Roberts CC. Glu cose resp onse to d iscontinu a-
m u cosa in vitro. Scand J Gastroenterol 1999;34(2):156–162. tion of p arenteral nu trition in p atients less than 3 years of age. JPEN J
21. Torosian MH . Periop erative nu trition su p p ort for p atients u nd ergo- Parenter Enteral Nutr 1996;20(2):120–122.
ing gastrointestinal surgery: critical analysis and recom m end ations. 49. Jeejeebhoy KN , And erson GH , N akhood a AF, et al. Metabolic stu d ies
World J Surg 1999;23(6):565–569. in total parenteral nu trition w ith lip id in m an. Com p arison w ith glu -
22. Sand strom R, Drott C, H yltand er A, et al. The effect of p ostop erative cose. J Clin Invest 1976;57:125–136.
intravenous feed ing (TPN ) on outcom e follow ing m ajor su rgery eval- 50. Cam eron JL, Cap uzzi DM, Zu id em a GD, et al. Acu te p ancreatitis w ith
u ated in a rand om ized stu d y. Ann Surg 1993;217(2):185–195. hyperlip em ia: evid ence of p ersistence d efect in lip id m etabolism . Am
23. Group TVATPN CS. Periop erative total p arenteral nu trition in su rgical J Med 1974;56:482–487.
p atients. N Engl J Med 1991;325(N o. 8):525–532. 51. Aarsland A, Chinkes D, Wolfe RR. H ep atic and w hole-bod y fat syn-
24. Brau nschw eig C, Levy P, Sheean P, et al. Enteral com p ared w ith p ar- thesis in hu m ans d u ring carbohyd rate overfeed ing. Am J Clin Nutr
enteral nu trition: A m eta-analysis. Am J Clin Nutr 2001;74(4):534–542. 1997;65:1774–1782.
25. Bjerke H S, Shabot MM. Glu cose intolerance in critically ill su rgical 52. Sam ra JS, Sum m ers LK, Frayn KN . Sep sis and fat m etabolism . Br J
p atients: relationship to total p arenteral nu trition and severity of ill- Surg 1996;83:1186–1196.
ness. Am Surg 1992;58:728–731. 53. Garber AJ, Vinik A, Creep s SR. Detection and m anagem ent of lip id
26. Wolfe RR, O’Donnell TF, Stone MD, et al. Investigation of factors d isord ers in d iabetic p atients. Diabetes Care 1992;15:1068–1073.
d eterm ining the op tim al glu cose infu sion rate in total p arenteral 54. Muscaritoli M, Cangiano C, Cascino A, et al. Exogenou s lip id clear-
nu trition. Metabolism 1980;29:892–900. ance in com pensated liver cirrohsis. JPEN J Parenter Enteral Nutr
27. Bu rke JF, Wolfe RR, Mu llany CJ, et al. Glu cose requ irem ents follow ing 1986;10:599–603.
burn inju ry. Ann Surg 1979;190:274–285. 55. Attm an PO, Sam u ellson O, Alau p ovic P. Diagnosis and classification
28. Rosm arin DK, Ward law GM, Mirtallo J. H yp erglycem ia associated of d yslipid em ia in renal d isease. Blood Purif 1996;14:49–57.
w ith high, continuous infu sion rates of total p arenteral nu trition d ex- 56. Carm en JL. Lip id abnorm alities and acu te p ancreatitis. Hosp Pract
trose. Nutr Clin Pract 1996;11:151–156. 1977;12:95–101.
29. H ostetter MK. Perspectives in d iabetes: hand icap s to host d efense: 57. Ed d leston JM, Shelly MP. The effect on seru m lip id concentrations of a
effects of hyperglycem ia on C3 and Cand id a albicans. Diabetes 1990;39: p rolonged infusion of p rop ofol. H yp ertriglycerid aem ia associated
271–275. w ith propofol ad m inistration. Intensive Care Med 1991;17:424–426.
30. Van Oss CJ, Bord er JR. Influ ence of interm ittent hyp erglycem ic glu- 58. Tsu guhiko T, Mashim a Y, Yam am ori H , et al. Intravenou s intralip id
cose levels on the phagocytosis of m icroorganism s by hum an granu- 10% vs 20% hyp erlip id em ia and increase in lip op rotein X in hu m ans.
locytes in vitro. Immunol Commun 1978;7:669–676. Nutrition 1992;8:155–160.
31. Kjersem H , H ilsted J, Mad sbad S, et al. Polym orp honu clear leucocyte 59. Messing B, Peynet J, Pou p on J, et al. Effect of fat-em u lsion p hosp ho-
d ysfu nction d u ring short term m etabolic changes from norm o- to lipid s on seru m lip op rotein p rofile d u ring 1 m o of cyclic total p ar-
hyp erglycem ia in typ e 1 (insu lin d ep end ent) d iabetic p atients. Infec- enteral nutrition. Am J Clin Nutr 1990;52:1094–1100.
tion 1988;16:215–221. 60. Carp entier YA. Intravascular m etabolism of fat em u lsions. Clin Nutr
32. Rayfield EJ, Ault MJ, Keu sch GT, et al. Infection and d iabetes: the case 1989;8:115–125.
for glucose control. Am J Med 1982;72:439–450. 61. Roulet M, Wiesel PH , Pilet M, et al. Effects of intravenou sly infu sed
33. Bagd ad e JD, N ielson KL, Bu lger RJ. Reversible abnorm alities in egg phospholipid s on lipid and lipoprotein m etabolism in postopera-
p hagocytic function in p oorly controlled d iabetic p atients. Am J Med tive trau m a. JPEN J Parenter Enteral Nutr 1993;17:107–112.
Sci 1972;263:451–456. 62. Haumont D, Richelle M, Deckelbaum RJ, et al. Effect of liposomal
34. Furnay AP, Zerr KJ, Gru nkem eier GL, et al. Continu ou s intravenous content of lipid emulsions on plasma lipid concentrations in low birth
insulin infusion red u ces the incid ence of d eep sternal w ound infec- weight infants receiving parenteral nutrition. J Pediatr 1992;121:
tion in d iabetic patients after card iac su rgical p roced u res. Ann Thorac 759–763.
Surg 1999;67:352–362. 63. Kalfarentzos F, Kokkinis K, Leu kad iti K, et al. Com p arison betw een
35. Pom p oselli JJ, Baxter JK, Babineau TJ, et al. Early p ostop erative glu - tw o fat em u lsions: Intralipid 30 cent vs intralip id 10 cent in critically
cose control pred icts nosocom ial infection rate in d iabetic patients. ill p atients. Clin Nutr 1998;17:31–34.
JPEN J Parenter Enteral Nutr 1998;22:77–81. 64. N ord enstrom J, Thorne A. Com p arative stu d ies on a new concen-
36. McCow en KC, Malhotra A, Bistrian BR. Stress-ind u ced hyp er- trated fat em u lsion: Intralip id 30% vs. 20%. Clin Nutr 1993;12:160–167.
glycem ia. Crit Care Clin 2001;17:107–124. 65. Drum l W, Fischer M, Ratheiser K, et al. Use of intravenou s lip id s in
37. Gold en SH , Peart-Vigilance C, Kao WH , et al. Periop erative glycem ic critically ill p atients w ith sepsis w ithou t and w ith hep atic failu re.
control and the risk of infectious com plications in a cohort of ad ults JPEN J Parenter Enteral Nutr 1998;22:217–223.
w ith d iabetes. Diabetes Care 1999;22:1408–1414. 66. Abbott WC, Grakau skas AM, Bistrian BR, et al. Metabolic and resp ira-
38. Van d en Berghe G, Wou ters PJ, Weekers F, et al. Intensive insu lin ther- tory effects of continuous and d iscontinu ou s lip id infu sions. Occu r-
ap y in the critically ill p atients. N Engl J Med 2001;345(19):1359–1367. rence in excess of resting energy exp end itu re. Arch Surg 1984;119:
39. Van Den Berghe G, Wou ters PJ, Bou illon R, et al. Ou tcom e benefit of 1367–1371.
intensive insulin therap y in the critically ill: insulin d ose versus 67. Ireton-Jones CS, Turner WWJ. The u se of resp iratory qu otient to
glycem ic control. Crit Care Med 2003;31:359–366. d eterm ine the efficacy of nu trition su p p ort regim ens. J Am Diet Assoc
40. Finfer S, Chittock DR, Su SY, et al. The N ICE-SUGAR Stu d y Investiga- 1987;87:180–183.
tors. Intensive versus conventional glu cose control in critically ill 68. Elia M, Livesey G. Theory and valid ity of ind irect calorim etry d u ring
p atients. N Engl J Med 2009;360:1283–1297. net lip id synthesis. Am J Clin Nutr 1988;47:591–607.
41. Am ato P, Keating KP, Qu ercia RA, et al. Form u laic m ethod s of esti- 69. Guenst JM, N elson LD. Pred ictors of total p arenteral nu trition-
m ating caloric requirem ents in m echanically ventilated obese ind uced lip ogenesis. Chest 1994;105:553–559.
p atients: a reap praisal. Nutr Clin Pract 1995;10:229. 70. Covelli H D, Black JW, Olsen MS, et al. Resp iratory failu re p recip itated
42. Btaiche IF, Khalid i N . Metabolic com p lications of p arenteral nu trition by high carbohyd rate load s. Ann Intern Med 1981;95:579–581.
in ad u lts, p art 1. Am J Health Syst Pharm 2004;61:1938–1949. 71. Agu ilaniu B, Gold stein-Shap ses S, Pajon A, et al. Mu scle p rotein
43. Brow n G, Dod ek P. Intravenou s insu lin nom ogram im p roves blood d egrad ation is severely m alnou rished p atients w ith COPD su bject to
glucose control in the critically ill. Crit Care Med 2001;29:1714–1719. short-term TPN . JPEN J Parenter Enteral Nutr 1992;16:248–254.
72. Rod riguez JL, Askanazi J, Weissm an C, et al. Ventilatory and m eta- 101. Bu chm an AL. Choline d eficiency d u ring p arenteral nu trition in
bolic effects of glu cose infu sions. Chest 1985;88:512–518. hu m ans. Nutr Clin Pract 2003;18:353–358.
73. Brooks MJ, Melnik G. The refeed ing synd rom e: an ap p roach to u nd er- 102. Bu chm an AL, Du bin M, Jend en D, et al. Lecithin increases p lasm a free
stand ing its com p lications and p reventing its occu rrence. Pharma- choline and d ecreases hepatic steatosis in long-term parenteral nutri-
cotherapy 1995;15:713–726. tion patients. Gastroenterology 1992;102(4 p t 1):1363–1370.
74. Solom on SM, Kirby DF. The refeed ing synd rom e: a review. JPEN J 103. Bu chm an AL, Am ent M, Sohel M, et al. Choline d eficiency cau ses
Parenter Enteral Nutr 1990;14:90–97. reversible hepatic abnorm alities in patients receiving p arenteral nutri-
75. N esbakken R, Reinlie S. Magnesiu m and p hosp horu s: the electrolytes tion: p roof of a hu m an choline requ irem ent: a p lacebo-controlled trial.
of energy m etabolism . Acta Anaesthesiol Scand 1985;29:60–64. JPEN J Parenter Enteral Nutr 2001;25:260–268.
76. Lichtm an MA, Miller DR, Cohen J, et al. Red u ced red cell glycolysis, 104. Roslyn JJ, DenBesten L, Pitt H A, et al. Resid ent research aw ard .
2, 3 d ip hosphoglycerate and ad enosine trip hosp hate concentration, Effects of cholecystokinin on gallblad d er stasis and cholesterol gall-
and increased hem oglobin-oxygen affinity cau sed by hyp ophos- stone form ation. J Surg Res 1981;30(3):200–204.
p hatem ia. Ann Intern Med 1971;74:562–568. 105. Jaw aheer G, Pierro A, Lloyd DA, et al. Gall blad d er contractility in
77. O’Connor LR, Wheeler WS, Bethu ne JE. Effect of hyp op hosp hatem ia neonates: effects of p arenteral and enteral feed ing [p ublished erratum
on m yocard ial p erform ance in m an. N Engl J Med 1977;297:901–903. app ears in Arch Dis Child Fetal Neonatal Ed 1995;73(3):F198]. Arch Dis
78. Kraft MD, Btaiche IF, Sacks GS. Review of the refeed ing synd rom e. Child Fetal Neonatal Ed 1995;72(3):F200–F202.
Nutr Clin Pract 2005;20:625–633. 106. Gu rll N J, Meyer PD, DenBesten L. The effect of cholesterol crystals on
79. Lu ckey A, Parsa C. Flu id and electrolytes in the aged . Arch Surg 2003; gallblad d er fu nction in cholelithiasis. Surg Forum 1977;28:412–413.
138:1055–1060. 107. Allen B, Bernhoft R, Blanckaert N , et al. Slu d ge is calciu m biliru binate
80. Beaty L, Pem berton D. Treatment of water, electrolyte, and acid-base disor- associated w ith bile stasis. Am J Surg 1981;141:51–56.
ders in the surgical patient. N ew York: McGraw -H ill Com p anies; 1994. 108. Coop er A, Ross AJ, O’N eill JA Jr, et al. Resolu tion of intractable
81. Weinsier RL, Kru m d ieck CL. Death resulting from overzealou s total cholestasis associated w ith total parenteral nutrition follow ing biliary
p arenteral nutrition: the refeed ing synd rom e revisited . Am J Clin Nutr irrigation. J Pediatr Surg 1985;20(6):772–774.
1980;34:393–399. 109. Rintala R, Lind ahl H , Pohjavu ori M, et al. Su rgical treatm ent of
82. Silvis SE, Paragas PD. Paresthesias, weakness, seizures, and hypophos- intractable cholestasis associated w ith total parenteral nutrition in
phatemia in patients receiving hyperalimentation. Gastroenterology prem atu re infants. J Pediatr Surg 1993;28(5):716–719.
1972;62:513–520. 110. Caniano DA, Starr J, Ginn-Pease ME. Extensive short-bow el syn-
83. Eliahou H E, Feng PH , Weinberg U, et al. Acetate and bicarbonate in d rom e in neonates: Ou tcom e in the 1980s. Surgery 1989;105:119–124.
the correction of u raem ic acid osis. Br Med J 1970;4:399–401. 111. H ofm ann AF. Defective biliary secretion d u ring total p arenteral nu tri-
84. Richard s CE, Drayton M, Jenkins H , et al. Effect of d ifferent chlorid e tion: p robable m echanism s and p ossible solu tions. J Pediatr Gastroen-
infu sion rates on plasm a base excess d uring neonatal p arenteral nu tri- terol Nutr 1995;20(4):376–390.
tion. Acta Paediatrica 1993;82:678–682. 112. Sitzm ann JV, Pitt H A, Steinborn PA, et al. Cholecystokinin p revents
85. Bau ghm an FA, Pap p JP. Wernike’s encephalop athy w ith intravenou s parenteral nutrition ind u ced biliary slu d ge in hu m ans. Surg Gynecol
hyperalim entation: rem arks on sim ilarities betw een Wernike’s Obstet 1990;170(1):25–31.
encep halopathy and the p hosp hate d ep letion synd rom e. Mt Sinai J 113. Teitelbaum DH , H an-Markey T, Drongow ski RA, et al. Use of chole-
Med 1976;43:48–52. cystokinin to p revent the d evelop m ent of p arenteral nu trition-associ-
86. Kitam u ra K, Takahashi T, Tanaka H , et al. Tw o cases of thiam ine d efi- ated cholestasis. JPEN J Parenter Enteral Nutr 1997;21(2):100–103.
ciency-ind u ced lactic acid osis d u ring total parenteral nu trition. 114. Tsai S, Strou se P, Drongow ski R, et al. Use of cholecystokinin-octap ep -
Tohoku J Exp Med 1993;171:129–133. tid e to prevent TPN -associated gallstone d isease. J Pediatr Surg 2005;
87. Sheld on GF, Petersen SR, Snad ers R. H ep atic d ysfu nction d u ring 40(1):263–267.
hyp eralim entation. Arch Surg 1978;113(4):504–508. 115. Beath SV, Davies P, Pap ad op ou lou A, et al. Parenteral nu trition-
88. Zam ir O, N ussbau m MS, Bhad ra S, et al. Effect of enteral feed ing on related cholestasis in postsu rgical neonates: m u ltivariate analysis of
hep atic steatosis ind u ced by total p arenteral nu trition. JPEN J Parenter risk factors. J Pediatr Surg 1996;31(4):604–606.
Enteral Nutr 1994;18:20–25. 116. Teitelbau m DH , Tracy T. Parenteral nu trition-associated cholestasis.
89. Pow ell EE, Cooksley WGE, H anson R, et al. The natu ral history of Semin Pediatr Surg 2001;10(2):72–80.
nonalcoholic steatohepatitis: a follow -up stud y of forty-tw o patients 117. Btaiche IF, Khalid i N . Parenteral nu trition-associated liver com p lica-
for u p to 21 years. Hepatology 1990;11:74–80. tions in child ren. Pharmacotherapy 2002;22:188–211.
90. Sax H C, Bow er RH . H ep atic com p lications of total p arenteral nutri- 118. Teitelbau m DH . Parenteral nu trition-associated cholestasis. Curr Opin
tion. JPEN J Parenter Enteral Nutr 1988;12(N o. 6):615–618. Pediatr 1997;9:270–275.
91. Low ry SF, Brennan MF. Abnorm al liver fu nction d u ring p arenteral 119. Cavicchi M, Beau P, Crenn P, et al. Prevalence of liver d isease and con-
nu trition: relation to infu sion excess. J Surg Res 1979;26:300–307. tributing factors in p atients receiving hom e parenteral nu trition for
92. N u ssbaum MS, Fischer JE. Pathogenesis of hep atic steatosis d u ring p erm anent intestinal failu re. Ann Intern Med 2000;132(7):525–532.
total p arenteral nu trition. Surg Annu 1991;23(Pt 2):1–11. 120. Kiristioglu I, Antony P, Fan Y, et al. Total p arenteral nu trition-associ-
93. Palom bo JD, Schnu re F, Bistrian BR, et al. Im p rovem ent of liver func- ated changes in m ouse intestinal intraep ithelial lym p hocytes. Dig Dis
tion tests by ad m inistration of L-carnitine to a carnitine-d eficient Sci 2002;47(5):1147–1157.
patient receiving hom e p arenteral nu trition: a case rep ort. JPEN J Par- 121. Yang H , Finaly R, Teitelbau m DH . Alteration in ep ithelial p erm eabil-
enter Enteral Nutr 1987;11:88–92. ity and ion transport in a m ouse m od el of total parenteral nutrition.
94. Richard son TJ, Sgou tas D. Essential fatty acid d eficiency in fou r ad u lt Crit Care Med 2003;31(4):1118–1125.
patients during total parenteral nutrition. Am J Clin Nutr 1975;28:258–263. 122. Tazuke Y, Drongow ski RA, Btaiche I, et al. Effects of lip id ad m inistra-
95. Cam pos AC, Oler A, Megu id MM, et al. Liver biochem ical and histo- tion on liver ap op totic signals in a m ou se m od el of total p arenteral
logical changes w ith grad ed am ounts of total parenteral nu trition. nu trition (TPN ). Pediatr Surg Int 2004;20(4):224–228.
Arch Surg 1990;125:447–450. 123. Tazuke Y, Kiristioglu I, H eid elberger KP, et al. H ep atic P-glycop rotein
96. Zagara G, Locati L. Role of total p arenteral nu trition in d eterm ining changes w ith total p arenteral nutrition ad m inistration [see com m ent].
liver insufficiency in patients with cranial injuries. Glucose vs glucose JPEN J Parenter Enteral Nutr 2004;28(1):1–6.
lip id s. Minerva Anestesiol 1989;55(12):509–512. 124. Tazuke Y, Teitelbau m D. Alteration of canalicu lar transp orters in a
97. Reif S, Tano M, Oliverio R, et al. Total p arenteral nu trition-ind uced m ou se m od el of total p arenteral nu trition. J Pediatr Gastroenterol Nutr
steatosis: reversal by p arenteral lip id infu sions. JPEN J Parenter Enteral 2009;48(2):193–202.
Nutr 1991;15:102–104. 125. Beale E, N elson R, Bu cciarelli R, et al. Intrahep atic cholestasis associ-
98. H eym an MB, Storch S, Am ent ME. The fat overload synd rom e. Rep ort ated w ith p arenteral nu trition in p rem atu re infants. Pediatric 1979;64:
of a case and literatu re review. Am J Dis Child 1981;135:628–630. 342–347.
99. Tao RC, Peck GK, Yoshim u ra N N . Effect of carnitine on liver fat and 126. Vileisis RA, Inw ood RJ, H u nt CE. Prosp ective controlled stu d y of p ar-
nitrogen balance in intravenou sly fed grow ing rats. J Nutr 1981;111: enteral nutrition-associated cholestatic jau nd ice: effect of protein
171–177. intake. J Pediatr 1980;96(5):893–897.
100. Yao ZM, Vance DE. The active synthesis of p hosp hatid ylcholine is 127. H eu bi JE, Wiechm ann DA, Creu tzinger V, et al. Tau rou rsod eoxycholic
requ ired for very low d ensity lipoprotein secretion from rat hepato- acid (TUDCA) in the prevention of total parenteral nutrition-
cytes. J Biol Chem 1988;263:2998–3004. associated liver d isease.[see com m ent]. J Pediatr 2002;141(2):237–242.
128. Teitelbaum DH, Han-Markey T, Drongowski RA, et al. Use of cholecys- 149. Lecciones JA, Lee JW, N avano EE, et al. Vascu lar catheter associated
tokinin to prevent the d evelopment of parenteral nutrition-associated fu ngem ia: Analysis of 155 ep isod es. Clin Infect Dis 1992;14:875.
cholestasis. JPEN J Parenter Enteral Nutr 1997;21(2):100–103. 150. Wid m er AF. Managem ent of catheter-related bacterem ia and
129. Teitelbaum DH, Tracy TF Jr, Aouthmany MM, et al. Use of cholecys- fu ngem ia in patients on total p arenteral nu trition. Nutrition 1997;13(4,
tokinin-octapeptide for the prevention of parenteral nutrition-associated Sup p l):18S–25S.
cholestasis. Pediatrics 2005;115(5):1332–1340. 151. Merm el LA. Prevention of catheter-related infections. Ann Intern Med
130. Capron JP, Gineston JL, H erve MA, et al. Metronid azole in p revention 2000;132:391–402.
of cholestasis associated w ith total p arenteral nu trition. Lancet 1983; 152. O’Grad y N P, Alexand er M, Dellinger EP, et al. Gu id elines for the p re-
1(8322):446–447. vention of intravascu lar catheter-related infections. Centers for Dis-
131. Ku d sk K, Croce M, Fabian T. Enteral versu s p arenteral feed ing: effects ease Control and Prevention. MMWR Morb Mortal Wkly Rep 2002;
on septic m orbid ity after blunt and penetrating abd om inal traum a. 51(RR-10):1–29.
Ann Surg 1992;215:503–513. 153. Krzyw d a EA, And ris DA, Ed m iston CE. Catheter infections: d iagno-
132. Iyer K, Sp itz L, Clayton P. N ew insight into m echanism s of p arenteral sis, etiology, treatm ent and p revention. Nutr Clin Pract 1999;14:178.
nu trition—associated cholestasis: role of p lant sterols. J Pediatr Surg 154. Coran AG, Spivak D, Teitelbau m DH . An analysis of the m orbid ity
1998;33(1):1–6. and m ortality of short-bow el synd rom e in the ped iatric age grou p .
133. Teitelbaum D, Drongow ski R, Sp ivak D. Rap id d evelop m ent of Eur J Pediatr Surg 1999;9(4):228–230.
hyp erbilirubinem ia in infants w ith the short bow el synd rom e as a cor- 155. Johnson PR, Decker MD, Edwards KM, et al. Frequency of Broviac
relate to m ortality: Possible ind ication for early sm all bow el transcatheter infections in pediatric oncology patients. J Infect Dis 1986;154(4):
p lantation. Transplant Proc 1996;28(5):2677–2678. 570–578.
134. Correia M, Gu im araes J, d e Mattos L, et al. Perip heral p arenteral 156. Merm el LA, Allon M, Bouza E, et al. Clinical p ractice gu id elines for
nutrition: an option for patients w ith an ind ication for short-term par- the d iagnosis and m anagem ent of intravascu lar catheter-related infec-
enteral nu trition. Nutr Hosp 2004;19(1):14–18. tion: 2009 u pd ate by the Infectiou s Diseases Society of Am erica. Clin
135. Foley MJ. Rad iologic p lacem ent of long-term central venou s periph- Infect Dis 2009;49:1–45.
eral access system ports (PAS Port): resu lts in 150 p atients. J Vasc 157. Attar A, Messing B. Evid ence-based p revention of catheter infection
Interv Radiol 1995;6(2):255–262. d u ring parenteral nu trition.[see com m ent]. Curr Opin Clin Nutr Metab
136. Dom ino K, Bow d le T, Posner K. Inju ries and liability related to central Care 2001;4(3):211–218.
vascular catheters: a closed claim s analysis. Anesthesiology 2004; 158. Onland W, Shin C, Fu star S, et al. Ethanol-lock techniqu e for p ersist-
100(6):1411–1418. ent bacterem ia of long-term intravascu lar d evices in ped iatric
137. And ris DA, Krzyw d a EA, Schu lte W, et al. Pinch-off synd rom e: a rare p atients. Arch Pediatr Adolesc Med 2006;160(10):1049–1053.
etiology for central venou s catheter occlu sion. JPEN J Parenter Enteral 159. Mouw E, Chessm an K, Lesher A, et al. Use of an ethanol lock to p re-
Nutr 1994;18(6):531–533. vent catheter-related infections in child ren w ith short bow el syn-
138. H inke DH , Zand t-Stastny DA, Good m an LR, et al. Pinch-off syn- d rom e. J Pediatr Surg 2008;43(6):1025–1029.
d rom e: a com p lication of im p lantable su bclavian venou s access 160. And rew M, Marzinotto V, Pencharz P, et al. A cross-sectional stu d y of
d evices. Radiology 1990;177(2):353–356. catheter-related throm bosis in child ren receiving total parenteral
139. Lane R, Matthay M. Central line infections. Curr Opin Crit Care 2002;8: nu trition at hom e. J Pediatr 1995;126(3):358–363.
441–448. 161. Klerk C, Sm orenburg S, Bu ller H . Throm bosis p rop hylaxis in p atient
140. Fau bion WC, Wesley JR, Khalid i N , et al. Total p arenteral nutrition p opu lations w ith a central venou s catheter: a system atic review. Arch
catheter sepsis: im pact of the team ap p roach. JPEN J Parenter Enteral Intern Med 2003;163(16):1913–1921.
Nutr 1986;10(6):642–645. 162. Werlin SL, Lausten T, Jessen S, et al. Treatm ent of central venou s
141. Reed CR, Sessler CN , Glau ser FL, et al. Central venou s catheter infec- catheter occlusions w ith ethanol and hyd rochloric acid . JPEN J Par-
tions: concepts and controversies. Intensive Care Med 1995;21(2):177–183. enter Enteral Nutr 1995;19(5):416–418.
142. Berenholtz S, Pronovost P, Lip sett P, et al. Elim inating catheter-related 163. Dw olatzky T, Berezovski S, Fried m ann R. A p rosp ective com p arison
blood stream infections in the intensive care u nit. Crit Care Med of the u se of nasogastric and percutaneous end oscopic gastrostom y
2004;32(10):2014–2020. tu bes for long-term enteral feed ing in old er p eop le. Clin Nutr 2001;
143. Dezfu lian C, Lavelle J, N allam othu B, et al. Rates of infection for sin- 20(6):535–540.
gle-lu m en versu s m u ltilu m en central venou s catheters: A m eta-analy- 164. Boulton-Jones J, Lew is J, Jobling J, et al. Exp erience of p ost-p yloric
sis. Crit Care Med 2003;31(9):2385–2390. feed ing in seriou sly ill p atients in clinical p ractice. Clin Nutr 2004;23:
144. Cow l C, Weinstock J, Al-Ju rf A. Com p lications and cost associated 35–41.
w ith parenteral nu trition d elivered to hospitalized patients throu gh 165. Ganga UR, Ryan JJ, Schafer LW. Ind ications, com p lications, and long-
either su bclavian or p erip herally-inserted central catheters. Clin Nutr term resu lts of p ercutaneou s end oscop ic gastrostom y: a retrosp ective
2000;19:237–243. stud y. S D J Med 1994;47(5):149–152.
145. Sitges-Serra A, Pu ig P, Linares J, et al. H u b colonization as the initial 166. Gaud erer ML, Ponsky JL, Izant RJ Jr. Gastrostomy without laparotomy:
step in an ou tbreak of catheter-related sep sis d u e to coagu lase nega- A percutaneous endoscopic technique. J Pediatr Surg 1980;15:872–875.
tive staphylococci d u ring p arenteral nu trition. JPEN J Parenter Enteral 167. Metheny N A, Eisenberg P, Sp ies M. Asp iration p neu m onia in p atients
Nutr 1984;8(6):668–672. fed throu gh nasoenteral tu bes. Heart Lung 1986;15(3):256–261.
146. King DR, Kom er M, H offm an J, et al. Broviac catheter sep sis: the natu- 168. Spain DA, DeWeese RC, Reynold s MA, et al. Transp yloric p assage of
ral history of an iatrogenic infection. J Pediatr Surg 1985;20(6):728–733. feed ing tubes in patients w ith head injuries d oes not d ecrease com pli-
147. Ku rkchu basche AG, Sm ith SD, Row e MI. Catheter sep sis in short- cations. J Trauma 1995;39(6):1100–1102.
bow el synd rom e. Arch Surg 1992;127:21–25. 169. Strong R, Condon S, Soling M, et al. Equal aspiration rates from postpy-
148. Sitges-Serra A, Linares J. Tu nnels d o not protect against venou s- lorus and intragastric-placed small bore nasoenteric feeding tubes: A ran-
catheter-related sep sis [letter]. Lancet 1984;1(8374):459–460. domized prospective study. JPEN J Parenter Enteral Nutr 1992;16:59–63.
CHAPTER
22
Complications of Immunosuppression
Niraj M. Desai and Christina L. Klein
■ INTRODUCTION com m on sid e effects are su m m arized in Table 22.1 (1). The
activation of T cells and the inhibitory sites of action for
Mod ern ad vances in m ed ical therapy have resu lted in a com m only u sed im m u nosu p p ressive agents are show n in
large nu m ber of ind ivid u als w ith a com p rom ised im m u ne Figu re 22.1 (2).
system . The cau se of im m u nod eficiency m ay be intentional
(im m u nosu p p ression ad m inistration to p atients w ith ■ Corticosteroids
organ transp lants or w ith autoim m une d isease), the u nin-
tend ed consequ ence of a particu lar therap y (chem otherapy Corticosteroid s w ere first used clinically in 1949 and , since
for cancer), or the result of a d isease state (large bu rns or that tim e, have been u sed for a variety of ind ications inclu d -
acqu ired imm u nod eficiency synd rom e [AIDS]). As a resu lt ing allergies, autoimmu ne d iseases, arthritis, asthma, can-
of the increasing num ber of patients receiving im m u no- cer therapies, neurosurgery, organ transplantation, and
sup p ressive agents, the d iagnosis, treatm ent, and p reven- numerous others. Steroid s are the most commonly pre-
tion of immunosuppression related complications has scribed im m u nosu ppressive m ed ication d ue to their effi-
become commonplace. This chapter first review s immuno- cacy in a variety of d iseases, long-stand ing experience w ith
suppressive med ications and their specific side effects. Com- their use, and low cost. They are u su ally u sed in high
monly occurring com plications of imm unosuppression are d oses w hen therap y is initiated or for the rap id treatm ent
then review ed from the perspective of the consulting sur- of im m u ne activation (asthm a exacerbation, organ rejec-
geon. A thorough understanding of these complications is tion). Dosing is often then tap ered to a m aintenance d ose
essential w hen provid ing care to these complex patients. or com p letely d iscontinu ed . Dexam ethasone, p red nisone,
p red nisolone, and m ethylp red nisolone are exam p les of
com m only u sed steroid s.
■ IMMUNOSUPPRESSIVE AGENTS Corticosteroid s have a variety of effects on the immune
Over the p ast five d ecad es, several classes of im m u nosu p - system. Most importantly, they inhibit the production of sev-
p ressive agents have been d iscovered , w ith many new eral cytokines by T cells and antigen presenting cells (APCs),
comp ou nd s becom ing part of routine clinical u se. These includ ing IL-1, IL-2, IL-3, IL-6, tum or necrosis factor-alpha,
m ed ications are p rim arily u sed for the p revention and and interferon-gamma. Steroid s initially enter the cell and
treatm ent of rejection and have allow ed for an im pressive bind to intracellular receptors. The steroid -receptor complex
im p rovem ent in the su rvival of solid organ transp lant then enters the nucleus and binds to sequences of deoxyri-
recip ients. In ad d ition, im m unosupp ressive med ications bonucleic acid (DN A) on the promoter region of cytokine
have been u sed increasingly for the treatm ent of au toim - genes called glucocorticoid response elements, and thereby
m u ne d iseases. Im m unosup pressive agents are often u sed block the transcription of those cytokines. In ad d ition,
in at high d oses for a short tim e p eriod as ind u ction ther- steroids inhibit the action of nuclear factor-kappa B, another
ap y, for the treatm ent of rejection, or the treatm ent of an key element in the cytokine response (3,4). Given the effect
au toim m u ne flare. They are also used on a chronic basis in on multiple cytokines, steroids inhibit T cell activation at
low er d oses as m aintenance therapy. The available m ed ica- several stages. Additional immunosuppressive effects of
tions can be classified into five m ajor categories: corticos- steroids include inhibition of monocyte migration and sup-
teroid s, calcineu rin inhibitors (CN Is), m am m alian target of pression of chemokine prod uction.
rap am ycin (m TOR) inhibitors, antiproliferative agents, and Given the ubiquitous nature of glucocorticoid receptors
antibod ies. The im m u nosu ppressive m ed ications and their in most human cells, corticosteroids are associated with
adverse effects on a variety of tissues. Transient side effects
can occur with short term use of high-dose steroids, such as
Niraj M. Desai: Department of Surgery, The Johns Hopkins hypertension and diabetes mellitus. However, severe compli-
University School of Med icine, Baltimore, MD 21205. cations occur with long-term use, even w hen steroids are
Christina L. Klein: Dep artm ent of Su rgery, Washington taken at low maintenance d oses. The metabolic side effects of
University School of Med icine, St. Lou is, MO 63110. steroids are hypertension, diabetes, hyperlipid emia, sod ium
227
Table 2 2 .1 Su m m a r y of im m u n osu p p r essive m ed ica t ion sid e effect s

Medication Side Effects
Corticosteroids Hypertension, glucose intolerance, hyperlipidemia, fluid retention, protein wasting, adipose weight gain,
cataracts, glaucoma, peptic ulcers, pancreatitis, osteoporosis, osteonecrosis, mood disturbances, psychosis,
acne, delayed wound healing
Cyclosporine Hypertension, glucose intolerance, hyperlipidemia, nephrotoxicity, electrolyte disturbances, neurotoxicity, gingival
hyperplasia, hirsutism
Tacrolimus Hypertension, glucose intolerance, hyperlipidemia, nephrotoxicity, electrolyte disturbances, neurotoxicity, alopecia
Sirolimus Hyperlipidemia, anemia, leukopenia, thrombocytopenia, mouth sores, gastrointestinal disturbances, lymphedema,
impaired wound healing, pneumonitis
Azathioprine Leukopenia, thrombocytopenia, gastrointestinal disturbances, pancreatitis
Mycophenolate mofetil/ Leukopenia, thrombocytopenia, gastrointestinal disturbances
mycophenolic acid
Antithymocyte globulin Fever, chills, rash, leukopenia, thrombocytopenia, allergic reactions
Intravenous immune globulin Fever, chills, rash, aseptic meningitis, acute renal dysfunction, hypersensitivity reaction
Muromonab-CD3 (OKT3) Fever, chills, rigors, headache, myalgia, hypertension, flash pulmonary edema, aseptic meningitis,
hypersensitivity reaction
Basiliximab/daclizumab Hypersensitivity reaction (rare)
Alemtuzumab Fever, rash, nausea, shortness of breath, chest discomfort, hypersensitivity reaction
Rituximab Fever, rash, nausea, shortness of breath, chest discomfort, hypersensitivity reaction
Adapted from Hardinger KL, Koch MJ, Brennan DC. Current and future immunosuppressive strategies in renal transplantation. Pharmacotherapy2004; 24:1159–1176, with permission.
FIGURE 22.1. Signaling pathways involved in

CD40 Signal three
Antigen presenting cell Cytokines T cell activation. Sites of inhibition by commonly
CD80/86 used immunosuppressive medications are indi-
cated in parentheses. (From Helderman J H,
MHC Goral S. Transplantation immunobiology. In:
IL-2R Danovitch GM, ed. Handbook of kidney transplan-
Signal two tation, 3rd ed. Philadelphia, PA: Lippincott Williams
Signal one
& Wilkins; 2001:17–38, with permission.)
CD28 CD154 IL-2R

(basiliximab, Other
daclizumab) cytokine
T cell receptors
CD4 receptor
Tyrosine kinase
CD3
(OKT3) mTOR
Tyrosine kinase (sirolimus,
everolimus)
T cell
Increased intracellular Ca++ Cyclin
Calcineurin
(cyclosporine,
tacrolimus)
Cell
Induction of cytokine and cycle
other T cell activation genes
(corticosteroids) (azathioprine,
mycophenolate,
T cell nucleus leflunomide)
Chapter 22 • Complications of Immunosuppression 229
and fluid retention, protein w asting, grow th retardation, and Table 2 2 .2 M ed ica t ion in t era ct ion s
adipose w eight gain. Gastrointestinal (GI) side effects include for cyt och rom e P450 IIIa
gastritis, duodenal ulcers, and pancreatitis. The ocular com- su bst r a t es—cyclosp or in e, t a crolim u s ,
plications are glaucoma and cataracts. Osteoporosis often a n d sirolim u s
affects vertebral bodies of the spine, while osteonecrosis often
Increased Immunosuppressant Decreased Immunosuppressant
affects the femoral head. Psychiatric effects such as mood dis-
Levels Levels
turbances and psychosis, cosmetic side effects including acne
Ketoconazole Rifampin
and the d evelopment of Cushingoid features, and delayed Fluconazole Rifabutin
wound healing are all observed with steroids (1,3–5). This Itraconazole Phenytoin
broad range of sid e effects associated w ith chronic steroid Voriconazole Phenobarbital
use, along with the development of more specific immuno- Erythromycin Carbamazepine
suppressive medications, has led to efforts to minimize or Clarithromycin St. John’s wort
completely avoid the use of steroids (6,7). However, for the Diltiazem Isoniazid
majority of patients with organ transplants and w ith autoim- Verapamil
mune disease, steroids remain a cornerstone of immunosup- Cimetidine
pressive therapy. Danazol
Grapefruit juice
Nefazodone
■ Calcineurin inhibitors Fluvoxamine
Amiodarone
The cu rrently available CN Is are cyclosp orine and
tacrolim u s (form erly know n as FK-506). Both agents Adapted from Hardinger KL, Koch MJ, Brennan DC. Current and future immunosup-
inhibit the activation and p roliferation of T lym p hocytes pressive strategies in renal transplantation. Pharmacotherapy2004;24:1159–1176,
by su p p ressing the p rod u ction of the cytokines inter- with permission.
leu kin-2 (IL-2), IL-4, interferon-gam m a, and tu m or necro-
sis factor-alp ha by T lym p hocytes. The agents are
biochem ically d istinct – cyclosp orine is an 11 am ino acid an y p atient via eith er an oral or su blin gu al rou te, even
cyclic p olyp ep tid e p rod u ced by the fu ngal sp ecies after m ajor abd om inal su rgery (1). Rath er than ad m inis-
Tolypocladium inflatum Gams and tacrolim u s is a m acrolid e tering intravenou s cyclosp orine, it is p referable to con-
antibiotic p rod u ced by the fu ngu s Streptomyces tsukubaen- vert a p atient from cyclosp orine to oral tacrolim u s if
sis. Both agents have d istinct cytop lasm ic bind ing p roteins absorp tion of d ru g is a concern in the p ostop erative set-
(im m u nop hilins), w ith cyclosporine bind ing to cyclop hilin ting. In contrast to cyclosp orine, w here ad m inistration
and tacrolimu s bind ing to FKBP-12. H ow ever, in both w ith food ten d s to increase bioavailability, ad m inistra-
cases, the d ru g-im m u nophilin com plex bind s calcineu rin, tion of tacrolim u s w ith food can d ecrease the rate and
and thu s inhibits its ability to u pregulate the activity of cer- extent of absorp tion.
tain nu clear regu latory proteins (1,4). Both agents have a Oral cyclosp orine and tacrolim u s are u su ally given
relatively narrow therap eu tic w ind ow and close m onitor- tw ice d aily. They are both m etabolized in the liver by the
ing of d rug levels is necessary to achieve a balance betw een cytochrom e P450 IIIA (CYP3 A) p athw ay and are excreted
efficacy and toxicity. in the bile. Potential d ru g interactions are im p ortant to rec-
The original oil-based oral cyclosp orine form u lation ognize, and vigilance in m onitoring d ru g levels is required
d ep end s u p on bile for absorp tion and has erratic absorp - w hen any agent is ad d ed or ad ju sted that ind u ces or
tion p atterns. In contrast, cyclosp orine m od ified (also inhibits CYP3 A levels (Table 22.2) (1). There is only m ini-
know n as cyclosp orine m icroem u lsion), d ep end s less on m al renal excretion of either d ru g and neither is signifi-
bile for absorp tion and exhibits increased bioavailability cantly affected by d ialysis. Cyclosp orine and tacrolim us
an d m ore consistent absorp tion. In term s of d osin g, the levels have trad itionally been m easu red as m orning trou gh
tw o cyclosp orine form u lations are not consid ered inter- levels; how ever an increasing trend has been to m easure
changeable. Ap p rop riate d ru g levels can som etim es be the cyclosp orine level 2 hou rs after oral d osing (C 2 level).
m aintained w ith a low er relative d ose of cyclosp orine The ap propriate therapeu tic levels d epend on the type of
m od ified , an d m on itoring of levels is m an d atory if the organ transp lant, the length of tim e since transplantation,
p atien t is changed to an altern ate form u lation. Intra- and other factors (8).
venou s cyclosp orine (nonm od ified ) is rarely u sed ; how - CN Is are associated w ith nu m erou s toxicities. N ephro-
ever w hen necessary, ap p roxim ately one-third of the toxicity is a critical sid e effect that is d ose d ep end ent and
total oral d aily d ose is ad m inistered intravenou sly either results from vasoconstriction of the afferent arteriole,
over 2 to 6 hou rs or by 24 hou r continu ou s infu sion. resu lting in a “p rerenal” typ e of renal d ysfu nction. In ad d i-
Tacrolim u s d oes n ot d ep end u p on bile for absorp tion an d tion, long term u se of CN Is can lead to the d evelopment of
has excellen t oral bioavailability. Du e to its read y absorp - interstitial fibrosis d u e to the p rod u ction of p rofibrotic
tion, tacrolim u s very rarely need s to be given intra- cytokines (4,9,10). Concomitant administration of CNIs with
venou sly w ith therap eu tic levels achievable in alm ost other nephrotoxic medications, such as aminoglycosid es,
amp hotericin B d eoxycholate, and nonsteroid al anti- of everolimus is 28 hours and typical d osing is tw ice d aily.
inflam m atory d ru gs, should be avoid ed . Intravenou s con- Both d rugs are m etabolized in the liver and counter trans-
trast shou ld be u sed cau tiou sly, taking sp ecific m easu res, ported to the gu t lumen lead ing to elimination in the feces.
su ch as hyd ration, ad m inistration of N -acetylcysteine or The CYP3 A pathw ay is involved in d rug metabolism; thus,
sod iu m bicarbonate, and p ossible ad ju stm ent of the CN I recognizing p otential d rug interactions is im portant (Table
d ose, to p rotect the kid neys. Another m ajor sid e effect that 22.2) (1).
often resu lts in the d evelop m ent of frank d iabetes is glu - A m ajor d istinction betw een m TOR inhibitors and the
cose intolerance. The incid ence of p ost-transp lant d iabetes CN Is is the lack of renal toxicity from vasoconstriction
is higher in those receiving tacrolim u s com p ared to those from u sing the form er. H ow ever, significant p roteinuria
on cyclosp orine (11). The d evelop m ent of d iabetes m ay be has been observed in som e ind ivid uals w ith the u se of
m ild and requ ire only d iet control, or it m ay be m ore m TOR inhibitors; thu s, they also have nep hrotoxic poten-
severe and requ ire an oral agent or insu lin to treat. tial. When com bined w ith a CN I, m TOR inhibitors ap pear
Other com m on sid e effects of CN Is inclu d e hyp erten- to actu ally increase the renal toxicity associated w ith the
sion, electrolyte abnorm alities, hyp erlip id em ia, and CN I (4). This effect is p robably m ost p ronou nced w ith
neu rotoxicity. H yp ertension, althou gh seen w ith both cyclosp orine, bu t is also seen w ith tacrolim u s. Given this
cyclosp orine and tacrolim u s, is often m ore severe w ith p otential renal toxicity, the com bined u se of a CN I and an
cyclosp orine. This sid e effect is d u e to both renal and m TOR inhibitor on a chronic basis is avoid ed .
p erip heral vasoconstriction. Electrolyte abnorm alities on Another im portant toxicity of m TOR inhibitors is hyp er-
CN Is inclu d e hyp erkalem ia d u e to im p aired renal excre- lipid em ia (hypercholesterolem ia and hypertriglycerid em ia)
tion of p otassiu m , and hyp om agnesem ia d u e to w asting affecting up w ard s of 50% of patients (4). In most instances,
of m agnesiu m in the u rine (4). H yp erlip id em ia is m ore the lipid abnormalities can be managed by placing the
often seen w ith cyclosp orine than w ith tacrolim u s. N eu - patient on either a H MG-CoA red u ctase inhibitor (“statin”)
rologic sid e effects are m ore often associated w ith or a fibrate d epend ing on the specific lipid abnormality. A
tacrolim u s, and m ay be m ild , su ch as trem or or head ache, uniqu e and interesting sid e effect of m TOR inhibitors is the
or m ay be severe, su ch as seizu res and p osterior reversible d evelop m ent of p ainfu l m ou th sores that are associated
encep halop athy synd rom e. Tw o com m on cosm etic sid e w ith high d ru g levels and generally resolve w ith d ose
effects that are sp ecific to cyclosp orine are gingival hyp er- red u ction. The m TOR inhibitors can also cau se hem ato-
p lasia and hirsu tism , w hile alop ecia is som etim es seen logic abnorm alities su ch as leu kop enia, throm bocytop enia,
w ith tacrolim u s (1). While the cosm etic sid e effects of and anem ia that m ay requ ire d ose red u ction or changing
cyclosp orine m ay seem m inor com p ared to the p atho- im m u nosu p p ression. Lym p hed em a is an increasingly rec-
p hysiologic on es m entioned above, they are im p ortant to ognized com p lication of m TOR inhibitors and can p resent
the p atient and can resu lt in m ed ication noncom p liance any tim e after initiation (1). Im p aired w ou nd healing is an
an d graft loss. Du e to a m ore favorable sid e effect p rofile, im portant sid e effect from the surgeon’s perspective that is
tacrolim u s has becom e the p referred CN I for m ost solid d iscu ssed later in this chap ter.
organ transp lant recip ients, and is alm ost exclu sively
u sed in p ed iatric p atients. Generic p rep arations of both
cyclosp orine and tacrolim u s are available and in com m on
■ Antiproliferative agents
u se. It is recom m end ed that frequ ent m onitoring of levels A variety of antiproliferative agents are used for immuno-
be p erform ed w hen a p atient is changed from brand ed to suppression. These agents w ork by inhibiting DNA synthesis
generic p rod u ct (or vice versa) to ensu re that the intend ed and therefore cell proliferation. Azathioprine, mycopheno-
therap eu tic range is m aintained . late mofetil (MMF), and mycophenolate sodium are used in
transplant recipients as part of maintenance immunosup-
pression, and in patients with autoimmune diseases. Other
■ Mammalian target of rapamycin inhibitors commonly used antiproliferative agents include cyclophos-
Sirolimus and everolimus are mTOR inhibitors. Sirolimus is phamide and methotrexate for treatm ent of cancer and
a macrocyclic antibiotic produced by the bacteria Strepto- im m u ne-m ed iated d iseases.
myces hygroscopicus, and everolimus is the 2-hydroxyethyl Azathioprine is a pu rine analog that inhibits lym p ho-
derivative of sirolimus. The mTOR inhibitors also bind to cyte and m yelocyte p roliferation. It is typ ically ad m inis-
FKBP-12 in the cytoplasm of cells (like tacrolimus); how ever, tered orally as part of a maintenance im m u nosu ppression
the mechanism of action is quite d ifferent. The d rug/ FKBP- regim en, althou gh intravenou s d osing at one-half the oral
12 complex inhibits mTOR, a key regulatory protein kinase d ose is occasionally necessary. Azathiop rine shou ld be
that controls cytokine-d epend ant cell proliferation (1). Like avoid ed , or the d osing red u ced significantly, if ad m inis-
the CN Is, the mTOR inhibitors require monitoring of d rug tered w ith allop u rinol or febu xostat, since xanthine oxid ase
levels to achieve proper therapeutic efficacy. is necessary for the conversion of azathiop rine to inactive
Both sirolimus and everolimus are available in oral form m etabolites. The m ajor sid e effect observed is hem atologi-
only and are read ily absorbed . The half-life of sirolimus is cal, w ith a reversible, d ose-d ep end ent leu kop enia and ane-
60 hours, allow ing for once d aily d osing, w hile the half-life m ia most com m only observed . In ad d ition, hep atotoxicity
and acu te p ancreatitis are rarely seen in p atients on aza- Intravenou s im m u ne globu lins (IVIGs) are also poly-
thiop rine, w ith both cond itions being reversible w ith clonal antibod y preparations that are com m only u sed to
tim ely cessation of therapy (1,4). treat au toim m u ne and inflam m atory d iseases, and are
MMF and mycophenolate sodium both become mycophe- increasingly being u sed in organ transp lant recipients.
nolic acid (MPA) in vivo. A product of several Penicillium IVIG is p rep ared by p ooling im m u noglobin G (IgG) anti-
sp ecies, MPA affects DN A rep lication by noncom p etitive bod y from thou sand s of norm al volu nteers. It has com plex
reversible inhibition of inosine m onop hosp hate d ehyd ro- im m u noregu latory p rop erties, bu t is not im m u nosupp res-
genase, an im p ortant enzym e for de novo gu anosine synthe- sive and therefore d oes not lead to the associated com p lica-
sis. Becau se lym p hocytes d epend u pon de novo gu anosine tions (16). As w ith antithym ocyte globu lin, infusion-related
synthesis, MPA has a m ore selective cytostatic effect on sid e effects are observed . When IVIG is u sed in high d oses,
lym p hocytes com p ared to other cell typ es that have a sal- self-resolving asep tic m eningitis can d evelop. The high
vage p athw ay. Both d rugs are prim arily ad m inistered osm otic load of the m ed ication can cau se tu bu lar inju ry
orally in tw o d ivid ed d oses, althou gh an intravenou s form that m ay lead to acu te renal d ysfu nction (4). Renal d ys-
of MMF can be given at the sam e d osing regim en. The fu nction associated w ith IVIG ad m inistration has m ost
m ajor sid e effects of both MMF an d m ycop henolate com m only been rep orted in the setting of rapid ad m inistra-
sod iu m are related to the GI tract and are generally d ose- tion and the u se of p rod u cts stabilized w ith su crose.
d ep end ent. N au sea, d iarrhea, and bloating are often seen, Currently there are several monoclonal antibod ies avail-
w hile esop hagitis and gastritis are u ncom m on and m ay be able that target the T lymphocyte. In contrast to p olyclonal
related to invasive cytomegalovirus (CMV) d isease. Evalua- antibod ies, each of these agents has a sp ecific target on the
tion of MMF-related GI d istress often includ es colonoscopy T lymphocyte that the antibod y bind s to and on w hich it
and m u cosal biop sy, and a sp ectru m of histologic changes exerts its mechanism of action. The old est of these agents is
is d escribed (12,13). H em atological sid e effects inclu d ing muromonab-CD3 (OKT3), a mouse monoclonal antibod y
anem ia, leu kop enia, and throm bocytop enia are also fairly against the hu man T cell surface molecu le CD3. OKT3 lead s
com m on and u su ally im p rove by tem p orary m ed ication to the rapid d epletion of T cells and blocks the action of acti-
d iscontinu ation and resu m p tion at low er d oses once vated cytotoxic T cells. Severe sid e effects w ith initial
cou nts recover (1,4). ad ministration are fairly common d u e to a cytokine release
synd rome that occu rs. Fever, chills, rigors, head ache, and
muscle pain are commonly observed in patients receiving
■ Antibodies OKT3, especially w ith the first few d oses. In patients that
Antibod ies are often ad m inistered for ind u ction therap y are flu id overload ed , “flash” pu lmonary ed ema can occur
in the critical early p eriod after transp lantation to and shou ld be closely monitored for. Volu me status shou ld
d ecrease the risk of acu te rejection and to allow for low er be optimized prior to ad m inistering this agent. An aseptic
overall intensity of m aintenance im m u nosu p p ression. meningitis picture has also been observed in patients
They are also u sed for the treatm ent of steroid resistant receiving OKT3 (4). Basilixim ab is a m onoclonal antibod y
acu te rejection. Antibod y therap ies can be d ivid ed into that targets the IL-2 receptor that is used for ind uction ther-
the p olyclonal p rep arations that have a broad range of apy only. This antibod y blocks the IL-2 recep tor on T cells,
antibod y sp ecificities, and the m onoclonal p rep arations preventing activation and p roliferation, bu t d oes not lead to
that target a single sp ecific m olecu le to evoke their m ech- d epletion and an associated cytokine storm (1).
anism of action. Antibody preparations approved for use in hematology,
Rabbit-d erived and horse-d erived polyclonal antithy- oncology, and autoimmunity are being used “off-label” in
mocyte globu lin p reparations are cu rrently available. They transplant. Alemtuzumab is an anti-CD52 antibod y that
both contain a variety of antibod ies against m any lym p ho- d epletes T and B lymphocytes and monocytes. It has been
cyte su rface antigens—these antibod ies bind to the su rface used for both induction therapy and for the treatment of
of the lym p hocyte, cau se d epletion, and thu s interfere w ith rejection (1). A prolonged depletion in the w hite blood cell
cell-m ed iated and hum oral im m u ne responses (1,14). This count can occur, w ith many patients still having abnorm ally
d epletion occurs by both com plem ent-d epend ent cell lysis low counts 6 to 12 months after receiving alemtuzumab (17).
and by m acrop hage phagocytosis. The sid e effects of this Rituximab is a monoclonal antibody d irected against the
med ication inclu d e infu sion related ones such as fever, CD20 marker on B cells and is used for prophylaxis and
chills, head ache, and rarely anaphylaxis. In ad d ition, treatment against antibod y-med iated immunity (1). Its use
severe lym p hocyte d ep letion and throm bocytop enia m ay in kidney transplantation has increased d ue to the growing
occu r, w hich can lim it the ability to safely ad m inister su c- number of transplants performed in sensitized and ABO-
cessive d oses (4). Lym phocyte counts rem ain abnorm ally incompatible recipients. Both alemtuzumab and rituximab
low for several m onths in m ost patients and m ay persist for have infusion-related sid e effects such as fever, rash, nausea,
several years in som e (15). Thus, it is im portant to rem em - shortness of breath, chest d iscomfort, and allergic reactions.
ber that recip ients of antithym ocyte globulin m ay d evelop Eculizumab, a humanized monoclonal antibod y specific for
com plications related to persistent lym phopenia w eeks, complement com ponent C5a, inhibits mem brane attack
months, or even years after treatm ent. complex formation and is approved for use in paroxysmal
nocturnal hemoglobinuria. This agent is under investigation of the global imm unosuppressed state of the patient. This
in kidney transplant recipients for desensitization protocols section w ill cover w hole bod y and organ system based prob-
and treatment of antibody mediated rejection (18). lems associated with immunosuppression, especially as they
pertain to the consulting surgeon involved in the care of
these patients.
■ Medications in development
The greater understanding of immune activation at the cellu-
lar level has allowed for the development of several new bio-
■ Infection
logics, including fusion proteins and small molecules. The The m ajority of the m orbid ity and m ortality from im m u no-
fusion proteins combine a receptor targeting a ligand of inter- su p p ression w as once p rim arily d u e to infection. These
est with the Fc portion of an IgG molecule. They target the infectiou s com p lications not only resu lted from com mon
“immune synapse” between the APC and the T lymphocyte p athogens seen in nonim mu nosu p p ressed p atients, bu t
(Fig. 22.1). The fusion protein LEA29Y (Belatacept), w hich often w ere cau sed by op p ortu nistic agents that attacked the
strongly binds to CD80 and CD86 on APCs and interrupts T immune d eficient host primarily. With experience, clinicians
cell activation, has completed phase III clinical trials in renal d eveloped effective p rophylactic strategies against the m ore
transplant recipients and is under governmental review. Ale- commonly seen infections. This experience, coupled w ith
facept, a fusion protein that binds to CD2 on T lymphocytes, the development of more T cell specific agents, decreased the
also inhibits T cell activation. It is approved for use in psoria- overall incidence of infectious complications. Despite these
sis and ongoing clinical trials are being conducted in trans- advances, infectious complications remain a major concern
plant patients. Early clinical experience w ith a monoclonal w hen caring for immunosuppressed individuals.
antibody against CD154 d emonstrated major thrombotic The variety of pathogens that have been observed in
events, including myocard ial infarction and stroke; thus, any immunosuppressed patients far exceed s w hat is seen in the
new agent w ill be carefully scrutinized for safety and efficacy “normal” host, w ith many of these opportunistic pathogens
prior to receiving approval for use in patients (19). only being observed in these individuals. Bacterial infections
Small molecule immunosuppressive drug development are often resistant to routinely used antibiotics because of
also continues with numerous agents being studied . Janus previous patient exposure to these agents or colonization of
kinase 3 (JAK3) is an important intracellular signaling pro- the patient w ith resistant bacteria during prolonged hospital
tein involved in cytokine med iated T cell proliferation (20). stays. Vancomycin resistant Enterococcus (VRE), methicillin-
Phase II clinical trials using a JAK3 inhibitor (CP-690550) in resistant Staphylococcus aureus (MRSA), and extend ed -spec-
renal transplant patients have demonstrated promising trum beta-lactamase producing Escherichia coli and Klebsiella
results compared to standard CNI-based regimens. Potential species are examples. Cystic fibrosis patients aw aiting lung
adverse effects includ e increased rates of CMV disease and transplantation can become colonized w ith Pseudomonas
BK virus nephropathy, as w ell as anemia (18). Protein kinase aeruginosa, Stenotrophomonas maltophilia, or Burkholderia cepa-
C (PKC) med iates signalling d ow nstream of the T-cell recep- cia that are resistant to beta lactams, aminoglycosides, and
tor, and PKC inhibitors are being stud ied in transplant. fluoroquinolones, lead ing to high morbid ity and mortality
Phase II trials involving tacrolimus w ithdrawal in renal after transplantation (22). Mycobacterial infection with
transplant patients receiving a PKC inhibitor (AEB071) w ere either Mycobacterium tuberculosis or atypical mycobacterium
halted due to an increased incidence of acute rejection. H ow - occurs far more frequently in im munosuppressed patients,
ever, PKC inhibitors are still under investigation as ad junc- but is still rare in developed countries (22).
tive therapy in both CNI and mTOR based regimens (18). Viral infections are often the consequ ence of reactiva-
Bortezom ib, a p roteosom e inhibitor approved for the tion of latent infections once the p atient has becom e
treatm ent of m u ltip le m yelom a, is being investigated off- im m u nosu p p ressed . In organ transp lant recip ients, an
label in kid ney transplant d esensitization protocols and for extrem ely problem atic viral infection w as CMV u ntil pro-
treatm ent of antibod y m ed iated rejection (21). It d irectly p hylaxis w ith antiviral therap y becam e rou tine. CMV d is-
targets the m atu re p lasm a cell, unlike other therapies cu r- ease can occu r as a viral synd rom e w ith fever, m alaise,
rently u sed for p revention and treatm ent of antibod y m ed i- leu kop enia, and throm bocytop enia, and it can also present
ated rejection. as a tissu e invasive d isease cau sing p neu m onitis, hepatitis,
retinitis, or GI tract d isease (22). Other viral d iseases d ue to
■ COMMON PROBLEMS ASSOCIATED Ep stein-Barr, herp es sim p lex, hu m an herp esviru s-6 and -7,
varicella zoster, resp iratory syncytial, influ enza, par-
WITH IMMUNOSUPPRESSION voviru s, and ad enoviru s are all d escribed (22).
The com plications that occur due to immunosuppression Invasive fu ngal infections are consid ered the m ost d iffi-
can affect any part of the bod y and are w id e ranging in their cult to treat infections in immu nosu pp ressed p atients. Pneu-
scope. Many of them are related to the previously mentioned mocystis jiroveci (formerly know n as Pneumocystis carinii)
sid e effects of a particular imm unosuppressive agent; how - causes a pneumonia that is characterized by hypoxemia
ever, additional complications occur that are the result of and d yspnea that is d isproportional to physical exam and
combination therapy w ith m ultiple agents or a consequence radiographic findings. This disease w as the initial d efining
illness in 63% of AIDS patients in 1987 and affected up to

15% of transplant recipients (22,23). Fortunately, effective
prophylaxis strategies have reduced these rates consid er-
ably. Candida species can cause mucocutaneous infection,
esophagitis, pyelonephritis, candidemia, endocard itis, brain
abscess, sinusitis, empyema, peritonitis, and wound infec-
tion. Aspergillus species most commonly cause lung and
upper respiratory tract infections, including sinusitis, tra-
cheobronchitis, necrotizing pneumonia, and empyema. Dis-
seminated d isease w ith brain abscess formation can occur as
can fungal ball formation in preexisting cavities. This organ-
ism is especially problematic for lung transplant recipients
(22,24). Cryptococcus neoformans most commonly causes cen-
tral nervous system disease and pulmonary disease. In
organ transplant recipients, there is a typical timeline for
occurrence of the m ore comm on fungal infections—Candida FIGURE 22.2. Abdominal CT scan demonstrating cancer metastases to the
in the first few weeks after transplantation, Aspergillus and liver and spleen of unknown primary origin in a recipient 4 months after kidney
Pneumocystis in the first 1 to 6 months after transplantation, transplantation. A CT scan 3 months earlier was normal.
and Cryptococcus after 6 months (22). Of course, these times
can vary based upon environmental factors and the overall
degree of immunosuppression in the ind ividual patient. Treatment of solid organ and skin cancers in patients on
im m u nosu pp ressive therapy shou ld follow established
guid elines for that p articu lar cancer. When possible, surgi-
■ Malignancy cal resection w ith ad equate margins should be performed to
Malignancy has been consid ered a greater p roblem in those control the p rim ary site of d isease. Ad d itional chem other-
receiving im m u nosu p p ression com p ared to the general ap y shou ld be ad m inistered w hen ind icated . Even w ith
pop u lation, w ith the absolute increase in risk d ep end ing an aggressive ap p roach to cancer treatm ent, the d evelop -
on the am ou nt of im m u nosu p p ression u sed and the typ e of m ent of recurrences and d istant m etastases is com m on on
malignancy (25–27). The m ajority of the stu d ies regard ing im m u nosu p p ressive therap y. If p ossible, consid eration
malignancy and im m unosupp ression are based u pon shou ld be given to imm u nosu p p ression red u ction or w ith-
transp lant recip ients, althou gh the find ings shou ld be d raw al. Regard less of w hether immunosuppressive therapy
app licable to all im m unosup pressed patients. In kid ney can be red uced , frequent monitoring for the d evelopment of
transp lant recip ients, the risk of d evelop ing cancers of the recurrence and metastases should be performed since the
colon, lu ng, p rostate, stom ach, esophagus, pancreas, ovary, propensity for rapid tumor spread in these patients is well
and breast are ap proxim ately tw o-fold greater than for the d ocumented (Fig. 22.2).
general p op u lation for the first 3 years follow ing transp lan- Tw o cancers that occu r in the general p op u lation bu t
tation. Testicu lar and blad d er cancers are increased three- are observed at m u ch higher rates in im m u nosu p p ressed
fold , and leu kem ia, hepatobiliary cancers, cervical and ind ivid u als d eserve ad d itional m ention. Post-transp lant
vu lvovaginal cancers are increased ap p roxim ately five-fold lym p hop roliferative d isease (PTLD) rep resents a variety
(28). Thu s, p revention strategies and screening m ethod s for of B lym p hocyte d isord ers ranging from m ild p olyclonal
these com m on cancers are likely to be even m ore relevant hyp erp lasia to m alignant m onoclonal lym p hom a. In the
for im m unosupp ressed ind ivid uals. m ajority of instances, the d isease ap p ears related to
Skin cancer is the most common malignancy in patients Ep stein-Barr viru s (EBV) m ed iated transform ation of B
on immunosuppressive therapy, causing serious morbid ity cells. The incid ence is estim ated betw een 1% and 10% of
and potential mortality. Several stu d ies have show n that the transp lant recip ients (30). In one series of 500 liver trans-
incid ence of skin cancers in transplant p atients is betw een p lant recip ients, 2.4% d evelop ed PTLD at a m ean of
40% and 80% after 20 years of immu nosu pp ressive therap y. 19.5 months after transp lantation (31). Patients may p resent
Com pared to the general population, m elanom a occu rs tw o w ith fever, fatigu e, w eight loss, a high EBV viral load , and
to four times more often, squamous-cell carcinoma occurs lym p had enop athy—either by p hysical exam or by im ag-
65 to 250 times more frequently, and basal-cell carcinoma ing stu d y. Patients can also p resent w ith solid organ
occu rs 10 tim es more often (29). As a result, the number of m asses, skin lesions, central nervou s system sym p tom s,
squamous-cell skin cancers exceed s the number of basal- and tonsil enlargem ent, esp ecially in child ren. Biop sy is
cell skin cancers in transplant recipients—the opposite of som etim es requ ired to confirm the d iagnosis, help d eter-
the general pop ulation. The key risk factor for d evelopm ent m ine the severity of the d isease, and d eterm ine therap y.
is u ltraviolet light exposu re, and patients on im m u nosu p- Treatm ent for m ild er form s is u su ally by im m u nosu p p res-
pression shou ld be cou nseled regard ing prevention strate- sion red u ction and antiviral therap y, w hile m ore m alig-
gies and carefu l skin exams to aid early d etection. nant variants requ ire chem otherap y and im m u notherap y
w ith anti-CD20 m onoclonal antibod y (32). Su rgical resec- exam ple, renal failu re p atients have a 10 to 20 tim es higher
tion or rad iation for d isease localized to a single lesion has mortality from card iovascular events than the general pop-
also been rep orted . ulation (36). H ow ever, several stu d ies have d emonstrated
Kaposi’s sarcom a is characterized by m u ltiple angiom a- that kid ney transplantation red uces this mortality risk
tou s lesions. There is an 80- to 500-fold increased incid ence w hen compared w ith ongoing d ialysis; thus, the potential
in im m u nosu p p ressed patients, and hu m an herpesviru s 8 harm caused by im m unosu ppressive therapy is overshad -
(H H V-8) has a cau sal role. Most patients w ith Kaposi’s sar- ow ed by the benefit of transplantation (37,38). Within the
com a have m u cosal or skin lesions, w ith m ost skin lesions pop ulation of immunosu ppressed patients, d ifferences in
occurring on the legs. Patients w ith visceral d isease u su ally card iovascular mortality have been observed betw een
present w ith lesions in the lungs, GI tract, or lym ph nod es grou ps of p atients on d ifferent immu nosup pressive med -
(29). Im m u nosu p p ression red u ction is first-line therap y for ications, im plying a contribu tory role of these m ed ications
Kaposi’s sarcom a, often resulting in d isease regression, to card iovascular complications. Perhap s the best w ay to
w ith chem otherap y being reserved for p ersistent d isease. assess the influ ence of immu nosup pressive agents on car-
d iovascular complications is by examining their impact on
the risk factors of card iovascular d isease (36).
■ Impaired wound healing Many of the immunosuppressive agents negatively
Im p aired w ou nd healing has been recognized to be a con- im pact card iovascular risk factors, such as d iabetes, hyper-
sequ ence of corticosteroid therap y since its introd u ction. tension, and hyperlipid emia. As mentioned previou sly, cor-
Several stu d ies have d ocu m ented that steroid ad m inistra- ticosteroid s, tacrolim us, and cyclosporine all cause d iabetes,
tion before or at the tim e of su rgery im p airs w ou nd healing hypertension, and hyperlip id em ia to varying d egrees. In
as measu red by tensile strength. H istologic stud ies have ad d ition, sirolimus and everolimu s also cause hyperlip i-
show n that steroid s interfere w ith the m igration of m ono- d emia to a greater extent than any of the other immunosup-
cytes and m acrop hages into the w ound , thus red u cing the pressive agents (1,4,36). Mod ification of risk factors throu gh
inflam m atory phase of w ound healing and red ucing the d iet and exercise is encouraged in patients on immunosup-
nu m ber of fibroblasts in the w ou nd . Stu d ies w ith corticos- pressive med ications. In ad d ition, the aggressive treatment
teroid s have d em onstrated a tw o-fold to five-fold increase of these risk factors w ith pharmacologic agents is w id ely
in w ou nd healing com p lications com pared to control sub- practiced . It is imp ortant to remember that p atients on long-
jects not receiving steroid s (5). stand ing immunosuppression w ill often have card iac d is-
More recently, m TOR inhibitors have been d ocu m ented ease, either as a result of native d isease or the result of these
to lead to im p aired w ound healing. This im pairm ent is med ications. Thus, noninvasive stress testing is recom-
related to the antip roliferative effects of the d ru g on m any mend ed prior to major elective proced ures in this patient
d ifferent cell typ es. From the transp lantation literatu re, it pop ulation.
has been d em onstrated that sirolim us cau ses a five-fold
increased incid ence of w ound infections, lymp hoceles, and
hernias in kid ney recipients, and an increased incid ence of
■ Gastrointestinal disease
bronchial anastomosis d ehiscence in lung recipients (33,34). Seriou s and often life threatening com p lications involving
Other anecd otal rep orts d escribe d ecreased w ou nd healing the entire GI tract have been reported in association w ith
in transplant patients on sirolimu s und ergoing other proce- immu nosu pp ressive therapy. Mu cosal u lceration lead ing to
d u res. Consid eration shou ld be given to tem porarily su b- bleed ing or perforation has been rep orted w ith the esopha-
stitu ting an m TOR inhibitor w ith a CN I at the tim e of an gus, stomach, small intestine, and colon. In ad d ition, biliary
operative p roced u re, or m uch earlier in the setting of elec- tract d isease and pancreatitis have also been frequently
tive su rgery. The u se of ad d itional closure m ethod s su ch as observed . The most commonly observed problems are gas-
retention su tu res shou ld be consid ered w hen op erating on trod uod enal ulcers and colon p erforations. H istorically, the
patients receiving an m TOR inhibitor. Other than steroid s initial culprit w as corticosteroid s, w ith numerous reports
and m TOR inhibitors, the other im m unosupp ressive m ed - d ocu m enting GI com plications in 10% to 30% of patients on
ications d o not significantly inhibit w ound healing. H ow - steroid s, and a high associated mortality (5,39). As addi-
ever, the consequ ences of w ound infections can be severe tional immunosuppressive agents w ere introduced, red uced
and thus vigilant observation for the d evelopment of wound d oses of corticosteroid s have been used and the incid ence of
com plications is recom m end ed . GI com plications has d ecreased . In ad d ition, the availability
of histamine recep tor antagonists and proton pump
inhibitors has allow ed for routine prophylaxis against gas-
■ Cardiovascular disease trod uod enal ulcer d isease and red uced the incid ence of
Card iovascular d isease in patients on imm unosuppression u pp er GI comp lications d ramatically (40).
is frequ ently observed , but the exact contribu tion of The highest rate of GI complications appears to occur in
im m u nosu pp ressive agents to card iovascu lar com p lica- recipients of heart and lung transplants. In one report, a 20%
tions is d ifficult to assess since preexisting d isease often car- rate of GI complications was observed within 30 days follow-
ries its ow n risk of card iovascular complications (35). For ing cardiac transplantation, including perforated duodenal
u lcer, p ancreatitis, colonic p neu m atosis, cholecystitis, d escribed elsew here in this chap ter. The systemic signs and
app end icitis, and colonic necrosis. Most of these p atients sym p tom s of CMV d isease inclu d e fever, m alaise, lethargy,
und erw ent su ccessfu l surgical intervention w ith over 90% and leu kop enia. CMV d isease of the GI tract is character-
surviving with normal GI function (41). Another report docu- ized by mu cosal u lcerations, erosions, and hem orrhage
mented a 40% rate of major GI complications follow ing lung that can affect the esop hagu s, stom ach, sm all bow el, and
transplantation, with 18% requiring an operative procedure colon. Lesions in these sites can lead to intestinal tract
and the remainder being managed with endoscopic interven- bleed ing or p erforation. The d iagnosis of CMV d isease in
tion or medications. Most of these GI complications occurred the intestinal tract is often m ad e by the p resence of GI
within the first month after lung transplantation (42). A more sym p tom s in the setting of a high viral load d etected by
recent analysis of renal transplant recipients documented a p olym erase chain reaction (44). H ow ever, significant GI
10% rate of severe GI complications following transplanta- tract CMV d isease m ay be p resent in the absence of sym p -
tion, with the most common problems being gastroduodenal toms, and investigation w ith end oscop y and biopsy is rec-
ulcers, colonic diverticulitis, and pancreatitis (43). om m end ed w hen CMV d isease is su spected (45).
Diagnosis of GI complications in immunosuppressed Treatm ent of GI tract CMV d isease is w ith system ic antivi-
ind ivid uals is often d ifficu lt because system ic signs su ch as ral therap y, and in severe cases, CMV im m u ne globu lin is
abd ominal pain, fever, and leu kocytosis are often minim al also ad m inistered . In som e situ ations, p atients m ay present
or absent d espite significant d isease. Abd ominal d istension w ith p erforation, and requ ire su rgical intervention, albeit
an d h yp oactive bow el sou nd s m ay be th e on ly signs of w ith a high m orbid ity and m ortality.
an abd ominal catastrophe. A high ind ex of su spicion is
required to d iagnose these GI complications, w ith frequent
abd ominal exams and the liberal u se of d iagnostic stu d ies
■ Chronic renal insufficiency and failure
being helpfu l. Plain rad iograp hs, compu ted tomography Renal insu fficiency and renal failu re are relatively com -
scans, contrast stud ies, selective arteriography, and upp er m on p roblem s that d evelop in p atients that receive long-
and low er end oscopy have all been reported to be helpfu l in term im m u nosu p p ressive therap y (10). Althou gh this is
making the d iagnosis in these patients. Once the d iagnosis p rim arily a consequ ence of CN I therap y, other com p lica-
of a major GI complication is mad e, immed iate and aggres- tions of im m u nosu p p ression su ch as hyp ertension, d ia-
sive intervention is required to optimize patient outcomes. betes, and dyslipidemia all contribute to the development of
When operative therapy is necessary, most experienced su r- chronic kid ney d isease. The prolonged use of cyclosporine or
geons ad vocate a conservative approach in term s of p er- tacrolimus leads to tubular atrophy, interstitial fibrosis, and
forming the simplest proced ure that controls the problem at arteriole hyalinosis in the kidney (46). This development of
hand . When small bow el resection is necessary, intestinal renal failure is most pronounced in recipients of nonrenal
continuity can usually be restored safely. H ow ever, w hen solid organ transplants, primarily d ue to the dependence on
large bow el resection is necessary, d iversion is preferred cyclosporine or tacrolimus to prevent rejection and thereby
over an anastomosis d ue to the risk of breakd ow n and the prolong graft and patient survival. Preexisting renal disease
d evelopment of further complications. Meticulous surgical from chronic hypoperfusion often contributes as w ell, partic-
care can lead to successful outcomes in patients w ith major ularly in heart and liver recipients. The cumulative incidence
im m u nosu pp ression related GI com p lications. of chronic renal failure in the United States at 5 years follow -
CMV is a com m on hu man p athogen that can lead to sig- ing transplantation is 10.9% for heart, 21.3% for intestine,
nificant d isease in im m unosupp ressed ind ivid u als, as 18.1% for liver, and 15.8% for lung recipients (Fig. 22.3) (47).
FIGURE 22.3. Cumulative inci-

dence of chronic renal failure in
recipients of nonrenal solid organ
transplants in the United States.
(From Ojo AO, Held PJ , Port FK,
et al. Chronic renal failure after
transplantation of a nonrenal organ.
N Engl J Med 2003;349:931–940,
with permission.)
Althou gh the m ajority of p atients on CN I therapy d o not Ad renal insu fficiency has been a m ajor concern in
d evelop chronic renal failure, most have some d egree of p atients receiving chronic glu cocorticoid therap y, since
impaired renal function (48). Patients on CN Is have a mean an early rep ort of d eath d u e to ad renal atrop hy in a
glomeru lar filtration rate that is approximately 40% less p atient receiving steroid s u nd ergoing an op eration (52).
than that of comparable patients not on CN Is, w ith this d if- Thu s, for m any years these p atients received ad d itional
ference being a result of red uced renal blood flow and there- large d oses of steroid s at the tim e of stress. H ow ever,
fore red uced ultrafiltration (9,46,49). Impaired renal function m ore recent stu d ies have d ocu m ented the safety of avoid -
may or may not be fully reflected in the plasma creatinine, ing “stress steroid s” in p atients receiving m aintenance
and it may require calculation or measu rement of the creati- p red nisone therap y of 5 to 10 m g/ d ay (53,54). “Stress
nine clearance to appreciate the d egree of renal d ysfunction steroid s” shou ld not rou tinely be given in the p eriop era-
present. When caring for these patients, it is important to tive setting to p atients on chronic steroid therap y, since
prevent intravascular volu me d epletion because hyp ov- their ad m inistration increases the risk of infection, d elays
olemia fu rther exacerbates the chronic effects of CN I on w ou nd healing and often significantly increases blood
renal fu nction. It is also recom m end ed that the u se of glu cose levels. When m inor or m od erate stress is
nephrotoxic med ications be avoid ed and interventions that exp ected , steroid s shou ld be continu ed at m aintenance
can further d istu rb renal function (i.e., intravenous contrast) d oses and the p atient shou ld be observed for signs of
be minim ized in patients receiving CN Is. ad renal insu fficiency, su ch as hyp otension, m yalgia,
The m anagem ent of d ialysis access in im m u nosu p - arthralgia, ileu s, fever, hyp onatrem ia, and eosinop hilia. If
pressed p atients is often qu ite comp licated . The preferred signs of ad renal insu fficiency d evelop , then a 24- to
long-term access is an arterial-venou s fistu la becau se infec- 48-hou r cou rse of “stress steroid s” shou ld be given. When
tious com plications are often severe in these p atients and a m ajor stressor occu rs in a p atient on chronic steroid
are m u ch m ore likely to occu r w ith artificial grafts, p eri- therap y, su ch as m ajor m u ltiorgan trau m a or a ru p tu red
toneal d ialysis catheters, and hem od ialysis catheters. The aortic aneu rysm , m ost clinicians agree that ad renal insu f-
id eal therap y for the recip ient of a nonrenal solid organ ficiency shou ld be investigated and ad m inistration of
transplant w ith renal failure is renal transplantation since “stress steroid s” shou ld be consid ered .
the patient is alread y receiving im m u nosup pressive ther-
apy. This is an increasingly com m on scenario w ith rep orts
ind icating good ou tcom es (50).
■ SUMMARY
The com plications of im m unosup pression rem ain a chal-
lenging p roblem for p atients and their healthcare
■ Endocrine abnormalities p rovid ers. While nu m erou s ind ivid u als have su ffered d ue
Diabetes mellitus is the most common endocrine abnormal- to im m u nod eficiency d isease states, there is little d ou bt
ity in patients on immunosuppression and is largely due to that the lives of others have been extend ed and enhanced
the use of steroids and CNIs. The diabetes is primarily due to by the availability of various m ed ications that allow for the
insulin resistance, although it may also result from dimin- control of au toimm u nity, transp lant rejection, and cancer.
ished insulin release. Risk factors for diabetes includ e The hop e for both grou p s of p atients is based on the grow -
African-American race, family history of d iabetes, obesity, ing nu m ber of therap eu tic agents com bined w ith the
hepatitis C, and older age. The contribution of steroids to dia- increased u nd erstand ing of the hu m an im m u ne system . It
betes is dose related—the majority of individuals receiving is to be hop ed that there w ill soon be a d ay w hen the nega-
high doses of steroids in the immediate period following tive consequ ences of im m unod eficiency w ill be prevented .
transplantation demonstrate impairment in glucose toler- Until then, a thorou gh u nd erstand ing of the com plications
ance; however, as the dose is red uced , most patients return to associated w ith im m u nosu p p ression com bined w ith an
near normal glucose levels. Since CNIs are most commonly aggressive ap p roach to d iagnosis and treatm ent w ill gener-
used in conjunction with corticosteroids, their contribution to ally lead to op tim al ou tcom es.
ind ucing diabetes is difficult to assess. It is generally accepted
that both cyclosporine and tacrolimus can cause diabetes and
that the risk is greater w ith tacrolimus. One analysis of renal ■ REFERENCES
transplant recipients demonstrated that 18% of patients 1. H ard inger KL, Koch MJ, Brennan DC. Cu rrent and fu tu re im m u nosu p -
receiving tacrolimus had developed d iabetes by tw o years p ressive strategies in renal transp lantation. Pharmacotherapy 2004;24(9):
1159–1176.
after transplantation compared to 8% of those receiving 2. H eld erm an J, Goral S. Transp lantation im m u nobiology. In: Handbook of
cyclosporine (11). Targeting lower therapeutic CNI levels as kidney transplantation, 3rd ed . Philad elp hia, PA: Lip p incott William s &
well as minimization of steroid dosing w ill often improve Wilkins, 2001:17–38.
3. H ricik DE, Alm aw i WY, Strom TB. Trend s in the u se of glu cocorticoid s
glycemic control (51). Management of patients with in renal transplantation. Transplantation 1994;57(7):979–989.
immunosuppression induced diabetes is similar to others 4. Danovitch G. Im m unosu pp ressive m ed ications and p rotocols for kid -
and includes diet and exercise, oral agents, or insulin. The ney transp lantation. In: Handbook of kidney transplantation, 4th ed .
Philad elp hia, PA: Lip pincott William s & Wilkins, 2005:72–134.
general goal is to maintain a hemoglobin A1c below 7% and 5. Diethelm AG. Surgical m anagem ent of com p lications of steroid ther-
to monitor and prevent diabetes related complications. ap y. Ann Surg 1977;185(3):251–263.
6. Matas AJ, Kand asw am y R, H u m ar A, et al. Long-term im m unosu p- 31. Norin S, Kimby E, Ericzon BG, et al. Posttransplant lymphoma–a single-
pression, w ithou t m aintenance p red nisone, after kid ney transp lanta- center experience of 500 liver transplantations. Med Oncol 2004;21(3):
tion. Ann Surg 2004;240(3):510–516; d iscu ssion 516–517. 273–284.
7. Wood le ES, First MR, Pirsch J, et al. A prospective, rand om ized , d ouble- 32. Verschu uren EA, Stevens SJ, van Im hoff GW, et al. Treatm ent of p ost-
blind , p lacebo controlled , m u lticenter trial com p aring early (7 d ay) transplant lym phoproliferative d isease w ith rituxim ab: the rem ission,
corticosteroid cessation versu s long-term , low -d ose corticosteroid ther- the relapse, and the com p lication. Transplantation 2002;73(1):100–104.
apy. Ann Surg 2008;248(4):564–577. 33. Dean PG, Lu nd WJ, Larson TS, et al. Wou nd -healing com p lications
8. N ash an B, Cole E, Levy G, et al. Clin ical valid ation stu d ies of N eoral after kid ney transplantation: a p rosp ective, rand om ized com p arison of
C(2) m onitoring: a review. Transplantation 2002;73(Su p p l 9):S3–S11. sirolim u s and tacrolim u s. Transplantation 2004;77(10):1555–1561.
9. Myers BD, Ross J, N ew ton L, et al. Cyclosp orine-associated chronic 34. Groetzner J, Kur F, Sp elsberg F, et al. Airw ay anastom osis com p lica-
nephrop athy. N Engl J Med 1984;311(11):699–705. tions in d e novo lung transplantation w ith sirolim u s-based im m u no-
10. Bennett WM, DeMattos A, Meyer MM, et al. Chronic cyclosporine su pp ression. J Heart Lung Transplant 2004;23(5):632–638.
nephrop athy: the Achilles’ heel of im m u nosu p p ressive therap y. Kidney 35. Kasiske BL, Chakkera H A, Roel J. Exp lained and u nexp lained ischem ic
Int 1996;50(4):1089–1100. heart d isease risk after renal transp lantation. J Am Soc Nephrol 2000;
11. Wood w ard RS, Schnitzler MA, Baty J, et al. Incid ence and cost of new 11(9):1735–1743.
onset d iabetes m ellitu s am ong U.S. w ait-listed and transp lanted renal 36. Boots JM, Christiaans MH , van H ooff JP. Effect of im m u nosu p p ressive
allograft recip ients. Am J Transplant 2003;3(5):590–598. agents on long-term su rvival of renal transplant recipients: focu s on the
12. Selbst MK, Ahrens WA, Robert ME, et al. Sp ectru m of histologic card iovascu lar risk. Drugs 2004;64(18):2047–2073.
changes in colonic biopsies in patients treated w ith m ycophenolate 37. Wolfe RA, Ashby VB, Milford EL, et al. Com p arison of m ortality in all
m ofetil. Mod Pathol 2009;22(6):737–743. patients on d ialysis, patients on d ialysis aw aiting transp lantation, and
13. Papad im itriou JC, Cangro CB, Lu stberg A, et al. H istologic featu res of recip ients of a first cad averic transp lant. N Engl J Med 1999;341(23):
m ycophenolate m ofetil-related colitis: a graft-versu s-host d isease-like 1725–1730.
pattern. Int J Surg Pathol 2003;11(4):295–302. 38. Ojo AO, H anson JA, Meier-Kriesche H , et al. Su rvival in recip ients of
14. Gaber AO, First MR, Tesi RJ, et al. Resu lts of the d ou ble-blind , rand om - m arginal cad averic d onor kid neys com pared w ith other recipients and
ized , m ulticenter, p hase III clinical trial of Thym oglobu lin versu s w ait-listed transp lant cand id ates. J Am Soc Nephrol 2001;12(3):589–597.
Atgam in the treatm ent of acute graft rejection episod es after renal 39. Penn I, Groth CG, Brettshneid er L, et al. Su rgically correctable intra-
transp lantation. Transplantation 1998;66(1):29–37. abd om inal com p lications before and after renal hom otransplantation.
15. Brennan DC, Flavin K, Low ell JA, et al. A rand om ized , d ou ble-blind ed Ann Surg 1968;168(5):865–870.
com parison of Thym oglobulin versu s Atgam for ind u ction im m uno- 40. Tropp m ann C, Pap alois BE, Chiou A, et al. Incid ence, com p lications,
sup pressive therap y in ad u lt renal transp lant recip ients. Transplantation treatm ent, and ou tcom e of u lcers of the u p p er gastrointestinal tract
1999;67(7):1011–1018. after renal transp lantation d u ring the cyclosp orine era. J Am Coll Surg
16. Kazatchkine MD, Kaveri SV. Im m u nom od u lation of au toim m u ne and 1995;180(4):433–443.
inflam m atory d iseases w ith intravenou s im m u ne globu lin. N Engl J 41. DiSesa VJ, Kirkm an RL, Tilney N L, et al. Managem ent of general su rgi-
Med 2001;345(10):747–755. cal com p lications follow ing card iac transp lantation. Arch Surg 1989;
17. Calne R, Moffatt SD, Friend PJ, et al. Cam p ath IH allow s low -d ose 124(5):539–541.
cyclosp orine m onotherap y in 31 cad averic renal allograft recipients. 42. Lubetkin EI, Lipson DA, Palevsky HI, et al. GI complications after ortho-
Transplantation 1999;68(10):1613–1616. topic lung transplantation. Am J Gastroenterol 1996;91(11):2382–2390.
18. Vincenti F, Kirk AD. What’s next in the p ip eline. Am J Transplant 43. Sarkio S, Halme L, Kyllonen L, et al. Severe gastrointestinal complications
2008;8(10):1972–1981. after 1,515 adult kidney transplantations. Transpl Int 2004;17(9):505–510.
19. Vincenti F. What’s in the p ip eline? N ew im m u nosu p p ressive d ru gs in 44. Good gam e RW. Gastrointestinal cytom egaloviru s d isease. Ann Intern
transplantation. Am J Transplant 2002;2(10):898–903. Med 1993;119(9):924–935.
20. N ashan B. Review of T-cell activation: im pact of Janu s kinase 3 inhibi- 45. Mayoral JL, Loeffler CM, Fasola CG, et al. Diagnosis and treatm ent of
tion. Transplantation 2003;75(11):1783–1785. cytom egaloviru s d isease in transp lant p atients based on gastrointesti-
21. Everly MJ, Everly JJ, Su sskind B, et al. Bortezom ib p rovid es effective nal tract m anifestations. Arch Surg 1991;126(2):202–206.
therapy for antibod y- and cell-m ed iated acu te rejection. Transplantation 46. You ng EW, Ellis CN , Messana JM, et al. A p rosp ective stu d y of renal
2008;86(12):1754–1761. stru cture and fu nction in p soriasis patients treated w ith cyclosporin.
22. Green M, Avery R, Preiksaitis J. Gu id elines for the p revention and Kidney Int 1994;46(4):1216–1222.
m anagem ent of infectiou s com plications of solid organ transplanta- 47. Ojo AO, H eld PJ, Port FK, et al. Chronic renal failu re after transp lanta-
tion. Am J Transplant 2004;10S:6–166. tion of a nonrenal organ. N Engl J Med 2003;349(10):931–940.
23. Morris A, Lund gren JD, Masu r H , et al. Cu rrent ep id em iology of Pneu- 48. Avitzur Y, De Lu ca E, Cantos M, et al. H ealth statu s ten years after p ed i-
m ocystis pneu m onia. Emerg Infect Dis 2004;10(10):1713–1720. atric liver transplantation–looking beyond the graft. Transplantation
24. Patterson TF, Kirkp atrick WR, White M, et al. Invasive asp ergillosis. 2004;78(4):566–573.
Disease spectru m , treatm ent p ractices, and ou tcom es. I3 Asp ergillu s 49. H olland er AA, van Saase JL, Kootte AM, et al. Beneficial effects of con-
Stu d y Group. Medicine (Baltimore) 2000;79(4):250–260. version from cyclosp orin to azathiop rine after kid ney transp lantation.
25. Trofe J, Beebe TM, Bu ell JF, et al. Posttransplant m alignancy. Prog Trans- Lancet 1995;345(8950):610–614.
plant 2004;14(3):193–200. 50. Coop ersm ith CM, Brennan DC, Miller B, et al. Renal transp lantation
26. Penn I. The effect of im m u nosu p p ression on p re-existing cancers. follow ing p reviou s heart, liver, and lu ng transp lantation: an 8-year
Transplantation 1993;55(4):742–747. single-center experience. Surgery 2001;130(3):457–462.
27. Feng S, Bu ell JF, Chari RS, et al. Tu m ors and transp lantation: The 2003 51. Gaston RS, Chand rakantan A. Diabetes m ellitu s after kid ney trans-
Third Annu al ASTS State-of-the-Art Winter Sym p osiu m . Am J Trans- plantation. Am J Transplant 2003;3(5):512–513.
plant 2003;3(12):1481–1487. 52. Fraser CG, Preu ss FS, Bigford WD. Ad renal atrop hy and irreversible
28. Kasiske BL, Snyd er JJ, Gilbertson DT, et al. Cancer after kid ney shock associated w ith cortisone therap y. J Am Med Assoc 1952;149(17):
transp lantation in the United States. Am J Transplant 2004;4(6): 1542–1543.
905–913. 53. Brom berg JS, Alfrey EJ, Barker CF, et al. Ad renal su p p ression and
29. Euvrard S, Kanitakis J, Clau d y A. Skin cancers after organ transplanta- steroid su p plem entation in renal transp lant recip ients. Transplantation
tion. N Engl J Med 2003;348(17):1681–1691. 1991;51(2):385–390.
30. Green M. Managem ent of Ep stein-Barr viru s-ind u ced p ost-transp lant 54. Brom berg JS, Baliga P, Cofer JB, et al. Stress steroid s are not requ ired for
lym phoproliferative d isease in recipients of solid organ transplanta- patients receiving a renal allograft and u nd ergoing op eration. J Am Coll
tion. Am J Transplant 2001;1(2):103–108. Surg 1995;180(5):532–536.
PART
III
Complications of
Thoracic Surgery
CHAPTER
23
Complications of Intubation,
Tracheotomy, and Tracheal Surgery
Kevin Fung and Norman D. Hogikyan
■ INTRODUCTION ■ Nasal complications

The d evelop m ent of orotracheal intu bation for the ad m in- N asotracheal intu bation is ind icated for su rgical p roce-
istration of anesthesia by William Macew en in 1878 w as d u res involving the oral cavity w hen end otracheal intu ba-
one of the m ost im p ortant ad vances in the history of su r- tion is expected to be p rolonged and w hen there is a
gery. With the p assage of tim e, how ever, acu te and chronic contraind ication to orotracheal intu bation.
com p lications of intu bation have becom e evid ent. Tra-
Acute Epistaxis
cheotom y is cu rrently ind icated in p atients for prolonged
ventilation in ord er to avoid long-term com p lications of Ep istaxis can occu r as a resu lt of inju ry to nasal m u cosa
intu bation. Benefits attribu ted to tracheotom y inclu d e d u ring nasotracheal intu bation. Inju ry can occur at the
enhanced p atient com fort, im proved pu lm onary toilet, level of the sep tu m (Kiesselbach p lexu s), lateral nasal w all
d ecreased ventilator-associated pneum onia, and acceler- (branches of internal m axillary artery), nasal tu rbinates, or
ated ventilator w eaning, althou gh strong su pportive evi- nasop haryngeal m u cosa. Treatm ent consists of d irect pres-
d ence is lacking (1). Althou gh som e view tracheotom y as a su re, anterior nasal p ack, top ical d econgestion, or otolaryn-
routine p roced u re, the potential com plications are signifi- gologic consu ltation for cau terization or p osterior nasal
cant and can be d evastating. As a consequ ence of p ro- p ack if p ersistent and p rofu se. The follow ing preventive
longed intu bation, acqu ired laryngotracheal stenosis can m easu res are su ggested .
occu r and is the m ost com mon ind ication for tracheal resec- 1. Preop erative recognition and correction of bleed ing d is-
tion. An u nd erstand ing of the com plications of p roced u res ord ers
involving the airw ay, includ ing intubation, tracheotom y, 2. Preoperative recognition of abnormal anatomy (i.e., d evi-
and tracheal su rgery, is im portant for all su rgeons. ated nasal septum, septal spur, nasal polyps, enlarged
adenoids)
■ Terminology 3. Ad equ ate top ical d econgestion (i.e., p seu d oephed rine,
oxym etazoline, cocaine)
The terms “vocal cord ” and “vocal fold” are used in various 4. Use of an ap p rop riate size tu be (i.e., internal d iam eter
w ays in the literature. Although both terms refer to the same 6.5 m m for m en and 6.0 m m for w omen) (4)
anatomical structures, vocal fold is the more correct contem- 5. Ju d iciou s u se of lu brication and heat to p rep are the tu be
porary term and will be used throughout the chapter. 6. Prop er techniqu e (i.e., angu lation of the tu be in an infe-
rior and p osterior d irection along the nasal floor)
■ INTUBATION Traditionally, it has been believed that in the presence of a
The su rgeon shou ld em p loy cu rrent techniqu es to achieve midline nasal septum, the right nostril should be used for
airw ay control d u ring ad m inistration of general anesthesia nasotracheal intubation because endotracheal tubes have a
and their associated com plications. Injury can occu r to any bevel on the tip such that the flat side faces to the left. A recent
part of the u p p er aerod igestive tract as a consequ ence of prospective study randomized nostril side in 128 patients
the intu bation event itself or as a consequence of the end o- undergoing nasotracheal intubation and found no difference
tracheal tu be resid ing in the airw ay. Inju ries are classified in the incidence of epistaxis or the difficulty of intubation (4).
accord ing to anatom ic location as w ell as tim ing⎯acu te
Chronic Sinusitis
(i.e., com p lications d u ring the intubation event) versu s
chronic (i.e., com plications w hile the patient is intu bated ) The ostiom eatal com plex rep resents the final com m on path-
(2,3). Pertinent risk factors for these injuries are su m m a- w ay of paranasal sinus d rainage. Its patency ensu res prop er
rized in Table 23.1. ventilation, aeration, m ucociliary clearance, and prevention
of effu sion and infection. In response to the presence of an
Kevin Fung and Norman D. Hogikyan: University of end otracheal tube in the nasal cavity, ed ema and inflamma-
Western Ontario, Lond on, Ontario, Canad a 800 tion of the lateral nasal w all m ucosa can lead to obstru ction
241
242 Part III • Complications of Thoracic Surgery
Table 2 3 .1 Risk fa ct or s for in t u ba t ion Preventive m easu res inclu d e p reop erative recognition of
com p lica t ion s p oor d entition or loose teeth and the u se of a tooth gu ard
d u ring intu bation. Inju ries m ay inclu d e d ental fracture,
Patient factors avu lsion, and p artial root avu lsion. It is im p ortant to
Unfavorable anatomy⎯short, thick neck ensure that an avulsed tooth is recovered in ord er to pre-
Abnormal anatomy⎯facial skeletal abnormality, trismus vent asp iration. Once the tooth is recovered , it shou ld be
Preexisting anatomic conditions⎯loose dentition, nasal septal p laced in saline and a d ental consu ltation shou ld be
deviation, cervical spine abnormalities
obtained to consid er reim p lantation (3). In the case of a par-
Preexisting medical conditions⎯gastroesophageal reflux disease (GERD),
tial fractu re, d ental restoration can be consid ered . In the
diabetes, coagulopathy
case of a p artial avu lsion, the tooth can be sp linted or w ired
Tube factors to an ad jacent tooth.
Tube too large
Cuff pressure too high Lip Injury
Coexisting nasogastric (NG) tube
The u pper lip can be lacerated if it is cau ght betw een the
Technical factors laryngoscop e blad e and the u p p er teeth. Likew ise, the
Forceful intubation
low er lip can be inju red as the laryngoscop e or the end otra-
Poor visualization of larynx
cheal tu be d rags the lip d ow n across the low er teeth.
Numerous intubation attempts
Sup erficial injuries can be treated conservatively w ith topi-
cal antibiotic ointm ent, and d eep er lacerations can be p ri-
m arily closed w ith attention to accu rate ap p roxim ation of
of the ostiomeatal complex, thereby resulting in effu sion the verm illion bord er.
and infection w ithin the paranasal sinuses. Obstru ction is
less com m on than previou sly thought. A stu d y of nasotra- Temporomandibular J oint Injury
cheally intubated patients d emonstrated sinus effusion on The tem porom and ibu lar joint can be d islocated as a conse-
ultrasound w ithin 3 d ays of intu bation in 31% of patients qu ence of forcefu l intu bation or d ifficu lt intu bation. At risk
(5). N o patients d eveloped sinusitis and all effusions are p atients w ith facial skeletal abnorm alities. Clinically,
resolved w ith removal of the tube. Longer-term intubation the m and ible is fou nd to be locked in op en p osition. The
is associated with a higher incidence of sinusitis. At risk are m echanism involves d isru p tion of the ligamentou s attach-
immunocompromised patients and head injury patients m ent of the tem p orom and ibu lar d isc to the cond yle and
w ith blood in the sinuses. Clinical m anifestations of sinusitis subsequ ent d isplacem ent of the d isc in the anterom ed ial
includ e purulent rhinorrhea, fever, facial pain, and unilateral d irection d u e to the p u ll of the lateral p terygoid m u scle.
facial sw elling. Pus obtained from the ostiomeatal complex Im m ed iate m anu al red uction u nd er anesthesia w ith m u s-
w ith end oscopic guid ance should be sent for culture and cle relaxation is recom mend ed . Postop eratively, the patient
sensitivity. Computerized tomography (CT) can d emon- shou ld be on a soft d iet for 2 w eeks.
strate effusion, but not all effusions represent true bacterial
sinusitis. Sinusitis is not an important source of sepsis unless Mucosal Injury
purulent sinusitis exists (2). Treatment involves removal of Inju ry to the m ucosa of the oral cavity or oropharynx can
the tube if possible, a 3-d ay course of topical d econgestant be su p erficial, d eep , or fu ll-thickness. Risk factors includ e
(i.e., pseud oephed rine, oxymetazoline, cocaine), and cul- u nfavorable anatomy (i.e., short, thick neck), lim ited neck
ture-d irected antibiotics, includ ing coverage for anaerobes extension, and trism u s. Inju ry can m anifest as laceration,
and Staphylococcus aureus. Occasionally, antral lavage is nec- hem atom a, infection, or p erforation. Su p erficial lacerations
essary in refractory cases. are treated conservatively w hile fu ll-thickness lacerations
are closed p rimarily. In the event of hem atom a, antibiotics
Nasal Alar Necrosis
shou ld be ad m inistered to p revent infection. Infection out-
Within hou rs, p ressu re necrosis can occu r from the nasotra- sid e the pharynx can lead to abscess form ation in the
cheal tu be or its secu ring ties. This rare com plication has retrop haryngeal or parapharyngeal spaces and can sp read
been rep orted in isolated case reports in the literature (6,7). via tissu e p lanes to the m ed iastinu m . N eck abscess shou ld
Su rgical correction of this d evastating cosm etic p roblem is be d rained su rgically. Perforation can be treated conserva-
extrem ely d ifficu lt. Prevention consists of proper cu shion- tively w ith nothing by m ou th (N PO) and antibiotics if iso-
ing betw een the nose, the tu be, and secu ring ties. lated , bu t shou ld be rep aired via an external cervical
ap p roach w ith closed su ction d rainage if large. Definitive
■ Oral cavity and oropharyngeal complications airw ay m anagem ent w ith p rolonged intu bation or tra-
cheotom y m ay be necessary. It is im p ortant to note that
Acute Dental Injury p ositive pressure ventilation in the presence of pharyngeal
Inju ry to d entition is a relatively com m on com p lication of inju ry can lead to su bcu taneou s em p hysem a, p neum om e-
intu bation, w ith a rep orted incid ence of 1 in 150 to 1 in d iastinu m , or p neu m othorax. These com p lications are d is-
1,500 intu bations (8). This is an avoid able com p lication. cu ssed in the section on com p lications of tracheotom y.
Chapter 23 • Complications of Intubation, Tracheotomy, and Tracheal Surgery 243
■ Acute laryngeal complications extubation, od ynophagia, w eak cough, and dysphagia.

Diagnosis is m ad e by bed sid e aw ake flexible laryngoscopy,
Mucosal Injury
revealing an immobile vocal fold, and the injured arytenoid
Mu cosal inju ry to the larynx can be su perficial, d eep , or cartilage is tipped anteriorly and med ially (i.e., intubation
transm u ral. Su p erficial m u cosal injury heals sp onta- injury) or posteriorly and laterally (i.e., extubation injury).
neou sly w ithin d ays. Minor m ucosal injury can resu lt in One w ould also expect to see contractile activity in vocal fold
trou blesom e bleed ing into the airw ay (3), and attem p ts at musculature w ith phonation on stroboscopic evaluation
suctioning can precipitate laryngeal ed em a. Su p erficial (11). Definitive d iagnosis is mad e by d irect laryngoscopy
mu cosal injury can also lead to vocal fold hem atom a, w ith palpation of the joint. Laryngeal electromyography
w hich resolves sp ontaneou sly and d oes not requ ire inter- (EMG) and CT scan may also be helpful (11). The most
vention excep t for voice rest. Vocal fold hem atom a is m ore important differential diagnosis to rule out is vocal fold
com m only left-sid ed becau se of right-hand ed intubators. paralysis from recurrent laryngeal nerve (RLN) injury. In
Deep m u cosal inju ry can resu lt in cartilage exp osu re w ith this case, the joint w ould be freely mobile, and treatment is
subsequ ent chond ritis. Sym ptom s includ e pain, d ysp ho- d iscussed in the section on complications of tracheal surgery.
nia, and od ynop hagia. Patients w ith severe ed em a are Voice therapy for d ysphonia associated w ith suspected ary-
treated w ith steroid s and antibiotics (9). Airw ay obstru c- tenoid d islocation or subluxation may be helpful in som e
tion requ ires d efinitive airw ay m anagem ent. Transm u ral patients (11), although manual endoscopic reduction is ind i-
laryngeal injuries should und ergo surgical repair via an cated as the d efinitive treatment (12).
open, laryngofissure approach. Laryngotracheal sep ara-
tion can occu r from intu bation in the setting of acu te laryn- Recurrent Laryngeal Nerve Injury
geal trau m a. Aw ake tracheotom y is the preferred m ethod The RLN typically enters the larynx betw een the cricoid
of airw ay control in this scenario. and thyroid cartilages near their articu lation and travels a
short d istance su bm u cosally. A cu ffed end otracheal tu be
Laryngospasm
m ight com p ress the nerve in this region. Patients m ay
Inad equate anesthesia on ind uction can lead to laryn- d evelop vocal fold p aralysis. Vocal fold p aralysis can be an
gospasm as a response to noxious stimuli anyw here in the acu te inju ry or can occu r as a consequ ence of long-term
bod y or stimulation of the airw ay. Aspiration of gastric con- intu bation and inap p rop riately high cu ff p ressu re. Patients
tents m ay be an inciting event. Laryngospasm can also occur com p lain of hoarseness and d ysp hagia p ostextu bation.
follow ing extubation. The mechanism of airw ay obstruction Principles of d iagnosis and m anagem ent of RLN injury are
is adduction of the true and false vocal folds, foreshortening d iscu ssed in the section on tracheal su rgery.
of the larynx, pressing the preepiglottic soft tissues against
the upper surface of the vocal folds, and complete closure of
the larynx (10). Because there is no air movement through the ■ Chronic laryngeal complications
larynx, there is no stridor despite obvious respiratory effort. Laryngeal inju ry is com m on follow ing p rolonged intu ba-
Management consists of immediate removal of the noxious tion. After 10 d ays of intu bation, the incid ence of erythema
stimulus, proper positioning (i.e., head extended on a flexed and vocal fold u lceration is 94% and 67%, resp ectively, and
neck) and positive pressure bag and mask ventilation. Light- m ost resolve w ithin 8 w eeks (13). The m echanism is
ening the anesthetic may restore tone to vocal fold abductors, straightforw ard : The posterior position of the end otracheal
thus enabling easier ventilation. If ventilation is not possible, tu be in the airw ay lead s to com pression of the m ucosa
a short-acting muscle relaxant such as succinylcholine should overlying the cricoid cartilage, m ed ial asp ect of the ary-
be administered, follow ed by maintenance of ventilation via tenoid cartilages, interarytenoid region, and su bglottis,
a mask or endotracheal intubation if necessary. Prevention lead ing to ischem ic necrosis w hen the force of com p ression
consists of ad equate anesthesia on ind uction, avoid ance of exceed s m u cosal cap illary p erfu sion p ressu re [i.e., 25 m m
unnecessary stimuli while the patient is lightly anesthetized, H g (14)]. Follow ing p rolonged p eriod s of intu bation, gran-
and application of topical lidocaine on the vocal folds fol- u lation and fibrosis can resu lt. Contribu ting factors inclu d e
lowing endoscopic laryngeal surgery. p resence of a nasogastric (N G) tu be, gastroesophageal
reflu x d isease (GERD), d iabetes, systemic vascu lar d isease,
Arytenoid Dislocation/Subluxation and m u ltip le intu bation attem p ts (3).
The p aired arytenoid s are irregu lar p yram id al-shap ed car-
tilages situ ated on the cricoid cartilage. The base of the ary- Laryngotracheal Stenosis
tenoid cartilage is concave and articu lates w ith the cricoid Acquired postintubation stenosis is traditionally classified as
via the cricoarytenoid joint. This synovial joint allow s rota- glottic, subglottic, and tracheal. The incid ence following pro-
tion and translation, w hich are fu nd am ental m ovem ents longed intubation has been found to be 4% after 5 to 10 days
for p rop er vocal fold fu nction. Inappropriately forcefu l or and 14% beyond 10 days (15). Patients are initially asympto-
blind intu bation can resu lt in arytenoid d islocation or matic but w ill d evelop symptoms weeks to months later.
su blu xation. Overall, how ever, this is a very u ncom m on Symptoms may include d ecreased exercise tolerance, dys-
com p lication. Clinical featu res inclu d e hoarseness after phonia, stridor, or dyspnea.
A B
FIGURE 23.1. Two different extremes of posterior glottic

stenosis. A relatively simple interarytenoid scar band (A) with
demonstration of mucosalized tract posterior to scar band by
passage of suction tip (B). Severe stenosis with dense posterior
commissure scarring (C). Definitive surgical management
depends on the location and extent of disease.
Accu rate aw ake flexible end oscop ic exam ination is cu ts throu gh the larynx and u p p er trachea is u sefu l to fu r-
important to d etermine laryngeal function and extent of ther d elineate the extent of stenosis for d iagnosis and surgi-
glottic involvement. If there is combined laryngeal and tra- cal p lanning. Im aging stu d ies, inclu d ing chest x-ray and
cheal d amage, the larynx should be ad d ressed first (16). lateral neck x-ray, as w ell as p u lm onary fu nction stu d ies,
Stenosis at the level of glottic larynx is typ ically posterior, at su ch as flow -volu m e loop s, are im p recise.
the level of the posterior vocal fold s, vocal processes of the Patients w ithou t a critical d egree of airw ay com p ro-
arytenoid cartilages, and interarytenoid region. A classifica- m ise can be m anaged in the elective setting. Initial airw ay
tion system for posterior glottic stenosis has been d efined m anagem ent in the setting of acu te resp iratory d istress
that ranges from a relatively sim ple interarytenoid scar inclu d es tem p orizing m easu res su ch as elevation of the
band (Figs. 23.1A and B) to d ense posterior commissu re head of the bed , cool hu m id ified air, nebu lized racem ic
scarring involving both cricoarytenoid joints (Fig. 23.1C) ep inep hrine, corticosteroid s, and heliox (i.e., a m ixtu re of
(17). Su bglottic stenosis occu rs at the level of the cricoid oxygen and heliu m that is low in d ensity and flow s m ore
cartilage, the narrow est p ortion of the airw ay (Fig. 23.2). efficiently throu gh a constricted airw ay). Critical airw ay
Becau se stenoses can occu r sim u ltaneou sly from the larynx stenosis that p reclu d es the p ossibility of intu bation is
to the trachea, it is im perative to end oscopically assess the m anaged w ith im m ed iate tracheotom y. If critical stenosis
entire upper resp iratory tract prior to surgical intervention. is not im m ed iately p resent, the p atient shou ld be trans-
Aw ake end oscopy in the outpatient clinic is the optimu m ferred to the op erating room w ith an experienced anesthe-
w ay to assess vocal fold m obility, w hile operative laryn- siologist, otolaryngologist, and op erating room staff.
goscopy and bronchoscopy u nd er general anesthesia is Available equipm ent should inclu d e a tracheotom y set,
often em p loyed to d eterm ine the level and d egree of inju ry, laryngoscop e, d ilators, rigid bronchoscop es, and end otra-
staging, and to confirm the d iagnosis. End oscopy of the cheal tu bes of variou s sizes. The bronchoscop e can be used
su bglottic larynx and trachea u sing top ical anesthesia in to establish an airw ay rapid ly and to d ilate the stenotic seg-
the outpatient clinic has also been d escribed as an alterna- m ent if necessary. If a tracheotom y is p erform ed , it shou ld
tive to op erative end oscopy (18). CT scan w ith fine (2 m m ) be d one through the area of m axim al tracheal d am age in
A B
FIGURE 23.2. A: Mild short-segment subglottic stenosis. B: Severe subglottic stenosis.
ord er to p reserve length for subsequ ent reconstru ction (19). anastomosis. The details of tracheal resection for postintuba-
A T-tu be can be used to stent the stenotic segm ent w hile tion tracheal stenosis are d iscussed elsew here (22). Basic
aw aiting su rgery. principles include:
Glottic stenosis. Posterior glottic stenosis is often a chal- 1. Accurate preoperative end oscopic evaluation of the
lenging clinical problem. Options for posterior glottic steno- anatom y of the stenotic segm ent
sis inclu d e d irected treatm ent at the area of stenosis itself, 2. Preservation of tracheal blood sup ply
su ch as sim p le excision of a scar band , scar excision w ith 3. Tension-free anastom osis, w hich m ay requ ire one or a
end oscop ic p ostcricoid ad vancem ent flap (20), op en p lace- com bination of variou s d escribed tracheal m obilization
m ent of a p osterior cartilage graft, or open scar excision via techniqu es (23)⎯finger d issection in the pretracheal
laryngofissu re w ith mu cosal graft and p ostoperative stent- p lane, su p rahyoid release, infrahyoid release, hilar
ing w ith either a Montgom ery T-tu be or a solid laryngeal release, reim p lantation of left m ainstem bronchu s, and
stent for 6 to 8 w eeks. Alternatively, enhancem ent of the air- neck flexion
w ay can be accom plished by red uction or release of glottic 4. Carefu l p atient selection (i.e., no m echanical ventilation,
tissu e that m ay or m ay not be d irectly involved w ith the op tim ization of m ed ical cond itions)
scar. This inclu d es proced u res such as arytenoid ectom y or
p osterior cord otom y. ■ Vocal process granuloma
Postintubation laryngeal granulomas arise at the medial
Subglottic stenosis. If the stenotic segm ent is 10 m m long, aspect of the arytenoids, where there is greatest mechanical
treatm ent can includ e end oscopic ap proaches, su ch as CO 2 compression from the endotracheal tube. Terms in the litera-
laser excision w ith a m icrotrap d oor m u cosal flap or rad ial tu re u sed to d escribe this d isease entity includ e “contact
incisions follow ed by d ilation. Ad d itionally, top ical m ito- ulcer,” “contact granuloma,” and “vocal process granuloma.”
m ycin-C is believed to be a u sefu l ad ju nct for lim iting Patients present w ith hoarseness after extubation, globus
restenosis (21). When an end oscopic approach is u nfavor- sensation (i.e., sensation of a lu m p in the throat), or laryn-
able, external ap p roaches are w arranted , su ch as cricoid d i- geal p ain. Aw ake laryngoscop y is d iagnostic (Figs. 23.3A
vision w ith cartilage graft or cricotracheal resection and and B). Typ ical end oscop ic find ings inclu d e proliferative
p rim ary thyrotracheal anastom osis. tissu e ap p earing p ale gray to red in color, p olypoid , nod u -
lar, or u lcerated in shap e, and a p osterior location. Biopsy
Tracheal Stenosis should be consid ered if the appearance is not typical or
Treatment depends on the length of the stenotic segment, there is no history of recent intu bation.
w hether the stenosis is circumferential or not, and whether it Thinking of these lesions as w ounds rather than as mass
is thin (membranous) or thick (fibrotic). Thin, short-segment lesions helps to guide treatment. Medical treatment includes
stenosis can be managed w ith endoscopic dilation and CO 2 proton pump inhibitors and antireflux behavior, based on the
laser excision. Long-segment stenosis is best managed exter- premise that subclinical reflux can irritate the posterior glottis
nally w ith segmental resection and primary end -to-end and delay healing of the granuloma (24). Voice therapy may
A B
FIGURE 23.3. Bilateral postintubation laryngeal granulomas with large right-sided lesion and smaller left-sided one (A) and unilateral
small granuloma (B).
be useful if voice abuse is felt to be an important contribut- the airw ay (tracheal stenosis), fu ll-thickness erosion into
ing factor impeding the healing process (25). These conser- the esop hagu s (tracheoesop hageal fistu la, TEF), tracheitis,
vative measures usually result in successful resolution. The or loss of cartilaginou s su p p ort (tracheom alacia). Tracheal
current otolaryngologic literature supports this nonsurgical stenosis is d iscu ssed in the section on laryngeal com p lica-
approach because of the high rate of recurrence follow ing tions of intu bation. TEF is d iscu ssed in the section on late
granuloma excision (25). com p lications of tracheotom y.
Several other treatm ents are d escribed in the cu rrent lit-
erature. There is w eak evid ence su pporting the u se of Tracheitis
antibiotics, system ic steroid s, and inhalational steroid s Mu cosal u lceration that becom es fu ll-thickness resu lts in
(25). Botu linu m toxin typ e A (Botox®; Allergan Inc., Irvine, exp osed cartilage that can becom e second arily infected .
CA) injection into the thyroarytenoid m u scle has d em on- Risk factors for tracheitis inclu d e p atient factors (i.e.,
strated som e efficacy (26). Rationale for this treatm ent is to ad vanced age, im m u nosu p p ression, d iabetes, reflu x) and
red u ce the force of vocal fold contact and therefore the tu be factors (i.e., tu be too large, cu ff p ressu re too high).
trau m a to the granu lom a. Injection of a large d ose, 10 to Treatm ent includ es broad -spectrum antibiotics and pu l-
15 U, p u ts the vocal fold at rest and allow s the granu lom a m onary toilet.
to heal. Others ad vocate an ad d itional, sm aller d ose, 3 to 5
U, injected into the contralateral thyroarytenoid m u scle to Tracheomalacia
p revent overcom p ensation d u ring the healing p hase (27). This entity is characterized by abnorm al d ynam ic tracheal
A tem p orarily w eak breathy voice is an exp ected sid e collap se second ary to inad equ ate stru ctu ral integrity of the
effect. tracheal cartilage. Destru ction of tracheal cartilage can
result from ischem ic inju ry from a cuffed end otracheal tube
and from tracheotom y (28). There is d istention of the air-
■ Tracheal complications w ay w ith insp iration and collap se w ith exp iration. If
Tracheal Rupture severe, tracheom alacia can m anifest as airw ay obstruction.
Intu bation can be com p licated by p enetration of the p oste- The airw ay can be stented w ith positive pressure ventila-
rior m em branou s w all or proxim al bronchu s, lead ing to tion or a long end otracheal tu be and can be byp assed w ith
false passage. Penetration can be caused by a long stylet a tracheotom y if the affected area is located high in the tra-
protru d ing beyond the tip of the end otracheal tube, force- chea. Definitive rep air consists of tracheal resection w ith
fu l intu bation, or m u ltiple intu bation attem pts. Clinical p rim ary anastom osis or tracheoplasty w ith cartilage graft.
manifestations inclu d e gastric d istension, p neum om ed i-
astinum , and p neu m othorax. This u ncom m on com p lica- ■ Tube complications
tion requ ires p rom p t airw ay control and su rgical rep air.
Long-term intu bation can resu lt in d am age to the tra- Cuff Laceration
chea in a fashion sim ilar that to the larynx. Pressu re Du ring the intu bation event, the cu ff of the end otracheal
necrosis of th e trach eal m u cosa lead s to u lceration , tu be can be lacerated . This m anifests as a cu ff leak d u ring
inflam m ation, cartilage exp osu re, granu lation, and fibro- ventilation. Once recognized , the tu be shou ld be changed
sis. Pressu re inju ry can m anifest as cicatricial scarring of p rom ptly.
Cuff Leak for w om en (29)], p u lse oxim etry, end -tid al CO 2 m onitoring,
A cu ff leak can also resu lt from a tu be that is too sm all for and fiberop tic bronchoscop y.
the p atient’s airw ay. In this scenario, the tu be shou ld be
changed prom ptly. ■ Special considerations
Tube Obstruction Laryngeal Mask Ventilation
Once the p atient is su ccessfu lly intu bated , the tu be itself This m od e of ventilation is com m only used in short elec-
cou ld obstru ct externally (i.e., patient biting on the tu be), tive cases. The m ain ad vantage is ease of u se. The laryngeal
internally (i.e., secretions, blood , foreign bod y), or as a m ask is p laced at the laryngeal inlet and the cu ff is inflated
resu lt of the tu be tw isted on itself. Obstru ction m anifests as to ensu re a seal. If the cu ff is overinflated or the m ask is
d ifficu lty w ith ventilation, increased ventilation p ressu re, p laced in a p oor p osition, m u cosal inju ry can occur in the
d ecreased breath sound s, hypoxia, and hypercap nia. If the form of abrasions, lacerations, ed em a, or u lcerations (30).
patient is biting on the tu be, a bite block shou ld be p laced Inju ry can m anifest as hoarseness or airw ay obstru ction.
and the level of anesthesia should be increased . Material
w ithin the tu be, if present, should be su ctioned . Any tw ists J et Ventilation
in the tu be shou ld be straightened , and the tube shou ld be In end oscop ic su rgery involving the larynx or trachea, ven-
secu red . Intu bation of a false p assage can m anifest in a sim - tilation can be achieved by jet ventilation through a rigid
ilar fashion. laryngoscop e or bronchoscop e and obviates the need for
translaryngeal intu bation. If the vocal fold s are not ad e-
Tube Displacement qu ately exp osed p rior to jet ventilation, the jet of air cou ld
Either the su rgeon or the patient rousing to noxiou s stim u li inju re the laryngeal or p haryngeal m u cosa, causing ed em a,
cou ld inad vertently extu bate the patient. Surgery of the hem atom a, or laryngosp asm . An ad equ ate expiratory
head and neck is prone to this problem becau se of the need p athw ay m u st be m aintained . If com p lete expiration d oes
to m anip u late these stru ctu res d u ring surgery. The follow - not occur betw een breaths or if excessive pressure is used ,
ing p reventive m easu res are recom m end ed : barotrauma can result, manifesting as pneumomed iastinum
or p neu m othorax.
1. Arrange the tu be and the ventilation circu it so that they
are secu red in a cephalad d irection w hen the op erative
field inclu d es both sid es of the neck (e.g., thyroid su r- ■ TRACHEOTOMY
gery, bilateral neck d issection).
2. Employ nasotracheal intubation for transoral proced ures. The w ord tracheotom y com es from the Greek and m eans
3. Secu re the tu be to the p atient’s d entition u sing a circu m - “cu tting the trachea.” Asclep iad es of Bithynia is cred ited
d ental stitch d u ring transoral p roced u res w hen nasotra- w ith p erform in g th e first trach eotom y in 100 B.C. The
cheal intu bation is not p ossible. ind ications for tracheotom y tod ay inclu d e u p p er airw ay
obstruction, long-term ventilation, and need for pulmonary
toilet. This procedure can be performed emergently, as in
■ Cervical spine injury laryngeal trauma, acute airw ay ed ema, or obstructing laryn-
It is im p ortant to recognize p atients at risk for d evelop ing a geal neoplasm, or electively, as in critically ill patients w ho
cervical sp ine inju ry as a consequ ence of intubation. These require long-term ventilation.
includ e patients w ith acute head trau m a and preexisting A retrosp ective review of 1,130 con secu tive op en tra-
cond itions (e.g., osteogenesis im perfecta, Dow n synd rom e, ch eotom ies p erform ed over a 10-year p eriod revealed
Morqu io synd rome, lytic bone lesions). If the cervical sp ine 49 major complications and eight d eaths d irectly attributable
is not cleared by rad iology, the neck shou ld be imm obilized to the procedure. The most common complications w ere tra-
in a hard collar and inline m anu al traction shou ld be cheal stenosis (21) and hemorrhage (9,31). Although some
app lied d u ring intu bation. Also useful in su ch cases are view tracheotomy as a routine procedure, the significance of
blind nasotracheal intu bation, fiberop tic bronchoscop ic the potential complications w arrants a detailed understand-
intu bation, or tracheotom y. ing. Com plications are classified into intraoperative, early
postoperative, and late postoperative.
■ Intubation of incorrect structure

■ Intraoperative complications
Incorrect p lacem ent of the end otracheal tu be into the
esop hagu s, m ainstem bronchus, or false passage can resu lt Damage to Adjacent Structures
in d isastrou s consequ ences. If unrecognized , this com p lica- As w ith any surgical proced ure, an intimate know led ge of
tion w ill lead to hypoxia, brain d am age, and d eath. The p ertinent anatomy is m and atory. Du ring tracheotomy, one
anesthesiologist m ust be able to recognize correct intratra- must be aw are of ad jacent structures, includ ing the RLN in
cheal tu be placem ent by d etection of equ al breath sound s, the tracheoesophageal groove, the com m on carotid artery
chest rise, tu be p osition at incisors [23 cm for m en, 21 cm and internal ju gular vein laterally, the thyroid isthmus and
anterior ju gu lar veins anteriorly, the innominate artery infe- Direct laryngoscopy and rigid bronchoscopy w ith saline
riorly, the lu ng apices inferolaterally, and the esophagu s lavage shou ld be p erform ed to extingu ish the fire, to re-
posteriorly. establish airw ay control, and to assess d am age.
Recurrent Laryngeal Nerve Injury

The RLN is in the tracheoesophageal groove and therefore ■ Early postoperative complications
should never be injured if d issection is precisely mid line. The early p ostop erative p eriod , beginning in the recovery
This complication is usually identified when there is d ys- room , is the setting for several im p ortant treatable com pli-
phonia after plugging the tracheostomy tube or decannula- cations. These can be thou ght of as p roblem s w ith the tra-
tion and is verified w ith ind irect laryngoscopy. Management cheotom y tu be, p roblem s associated w ith air ou tsid e the
of RLN injury is d iscussed in the section on complications of tracheobronchial tree, and other p roblem s.
tracheal surgery.
Tube Problems
Esophageal Injury
Cannula obstruction. The tracheotom y tu be itself can be ob-
Transm u ral inju ry to the p osterior w all of the trachea can
stru cted by blood , secretions, or m u cu s. This p roblem is
extend into the esophagu s. Managem ent consists of
m anifested clinically by d ecreased bilateral breath sou nd s
prom p t airw ay stabilization follow ed by su rgical rep air.
and hyp oxia. Cannu la obstru ction is easily m anaged w ith
TEF can also be a long-term com p lication of tracheotom y
su ction or rem oval and cleaning of the inner cannu la. Pre-
and is d iscu ssed later in this section.
vention of obstru ction is achieved by m eticu lou s tra-
Hemorrhage cheostom y care, inclu d ing hu m id ified air and frequ ent
su ctioning after instillation of 1 to 2 cc of sterile saline (3).
Minor hemorrhage can be life-threatening if it interferes
w ith the airw ay. Bleed ing usually originates from the ed ges Accidental decannulation. When accid ental d ecannu lation
of the thyroid isthmus if this structure is divided during the occu rs, it is im p ortant for the su rgical staff to rep lace the
procedure. Depend ing on surgeon preference, the thyroid tu be using the p roper introd ucer and to confirm placem ent
isthmus can be divided sharply and suture ligated, carefully by verifying good ventilation or w ith flexible end oscop y
divided w ith monopolar cautery, or left intact. Whatever the throu gh the tu be. A tu be that is blind ly p laced by w ell-
technique chosen, it is ad visable to check hemostasis at this m eaning p aram ed ical p ersonnel can resu lt in false p assage.
site prior to incision of the trachea in ord er to avoid bleed ing Prevention of d ecannulation is achieved by securing the tra-
into the airw ay and to decrease risk of airw ay fire associated cheostomy tube to the patient with suture and tracheostomy
w ith the use of cautery in proximity to an open airw ay (32). ties. Anticip ation is p aram ou nt in cases in w hich recannu-
Major hem orrhage from great vessels is life-threatening. lation m ay be d ifficu lt, su ch as in obese p atients w ith abun-
Bleed ing from the innom inate artery is d iscussed in the d ant cervical subcutaneous tissue, in difficult tracheotomies,
section on tracheoinnom inate artery fistu la (TIF). Bleed ing and in p ed iatric cases. In su ch cases, the su rgeon can con-
from the internal ju gu lar vein or comm on carotid artery is sid er placem ent of gu id e sutures to assist w ith recannula-
managed w ith recognition of the inju ry, proxim al and d is- tion. N onabsorbable su tu res can be p laced arou nd ad jacent
tal vascu lar control, and rep air or ligation by a su rgeon tracheal rings, brou ght ou t of the w ou nd on either sid e of
w ith ap p rop riate exp ertise. the tracheostom y tu be, and taped to the skin. In the event of
d ecannulation, manual tension of these sutures w ould bring
Airway Fire
the airw ay to the skin to p erm it easy recannu lation. The
Supplemental oxygen may be present in the airw ay, origi- Björk flap is an inferiorly based flap of anterior tracheal w all
nating from the ventilator through the endotracheal tube or at the tracheostom a that is su tu red to the overlying su bcu -
from mask ventilation if an awake tracheotomy is performed taneou s tissue; it is another useful techniqu e in cases w ith
und er local anesthesia. In either scenario, the surgeon should the p otential for d ifficu lt recannu lation (34).
be aware that an electrical arc from electrocautery, in the pres-
ence of supplemental oxygen, can result in airw ay fire. Air- False passage. Consequ ences of the tracheotomy tube being
way fire is a devastating but rare complication that has been in the subcutaneous tissue betw een the skin and the trachea
reported in the literature (32,33). Combustion is easily avoid - inclu d e su bcu taneou s em p hysem a, p neu m om ed iastinu m ,
able with proper precautions. There should be open commu- p neu m othorax, and hyp oventilation (i.e., loss of airw ay).
nication betw een the anesthesiologist and the surgeon, This problem m ay occu r w ith initial tube placem ent or by
particularly at the time of surgical entry into the airway. retraction of the d istal end of the tube w ith patient m ove-
Electrocau tery sh ou ld not be u sed in the p resence of an m ent or tu be m anip u lation. Managem ent consists of
oxygen-enriched environment and potentially combustible p rom p t recognition, re-establishm ent of the airw ay, and
material. In the event of airw ay fire, supplemental oxygen treatment of the com plication. In the early postoperative pe-
shou ld be im m ed iately d iscon tin u ed . All p otentially riod , the tracheotom y tract is not w ell form ed , and there-
flam m able m aterial sh ou ld be rem oved from th e p atient, fore, recannu lation shou ld be p erform ed w ith ap propriate
inclu d ing the end otracheal tu be and su rgical d rap es. lighting, p atient p ositioning, and equ ip m ent.
Air outside the tracheobronchial tree. As a consequ ence of the d evelop m ent of tracheal stenosis inclu d e excessively large
surgery itself, p ositive p ressu re ventilation into a false p as- op ening into the trachea, neglected infection or chond ritis,
sage, or inju ry to pleura, air can d issect into variou s tissu e and excessive traction or m ovem ent of the tracheotom y
p lanes, resu lting in su bcu taneou s em p hysem a, p neu m o- tu be. Som e au thors also cite sp ecific tracheostom a tech-
m ed iastinu m , or p neu m othorax. These com p lications are niqu es (i.e., inferiorly based Björk flap , excision of w ind ow,
u ncom m on (incid ence of 0.34%) (31). They share sim ilar and H -shap ed w ind ow ) as risk factors for d evelopm ent of
mechanisms⎯excessive d issection of tissu e planes, cannu la tracheal stenosis (38). Tracheal stenosis follow ing tra-
blockage, assisted ventilation w ith excessive pressu re (35), cheotom y can be classified anatom ically into su p rastom al
excessive cou ghing against a mechanical ventilator, ru p tu re (su bglottic), stom al, and infrastom al. Som e p atients pres-
of subpleural bleb, and d iscrepancy betw een size of tracheal ent early, w ith granu lation tissu e at the tip of the cannu la.
opening and size of cannu la. Prevention consists of avoid - Granu lation occu rs as a resu lt of friction of the tip against
ing u nnecessary paratracheal d issection, creating an op en- the tracheal m u cosa. Most p atients p resent follow ing
ing into the trachea that is sim ilar in size to that of the d ecannu lation. Com p laints inclu d e shortness of breath,
cannu la, and avoid ing tight closu re of the tracheotom y site. exertional d ysp nea, cou gh, or bip hasic strid or and resp ira-
We d o not close the su rgical w ound arou nd the cannu la. tory d istress if severe. Sym p tom s m ay be exacerbated w ith
a viral resp iratory illness and m ay m im ic bronchitis,
Subcutaneous emphysema. This com plication is herald ed by asthm a, or p neu m onia.
the p resence of neck sw elling and crepitu s. One m u st first
exclu d e p neu m om ed iastinu m and p neu m othorax. Man- Fistulae
agem ent inclu d es rem oval of skin su tu res, replacem ent of Erosion of the tracheotom y tube into an ad jacent stru ctu re is
cannu la w ith one of a larger size, insertion of a cu ffed tu be, a d read ed , potentially life-threatening, and preventable
ad equ ate sed ation, and ventilation of the p atient. complication. The tube can erod e anteriorly into the innom-
inate artery (TIF) and posteriorly into the esophagus (TEF),
Pneumomediastinum and pneumothorax. Managem ent in-
and d ecannu lation can resu lt in persistent tracheocuta-
cludes observation, chest tube placement, adequate sedation,
neous fistula if the w ound d oes not heal completely. Mecha-
or red uction in positive end -expiratory pressure (PEEP).
nisms includ e a tracheotomy that is too low (i.e., below the
third tracheal ring), a cu ff that is inflated too high, and local
Other problems. In p atients w ith chronic u pp er airw ay ob-
w ou nd healing p roblem s (i.e., infection, irrad iation, and
stru ction, tracheotom y resu lts in im m ed iate relief of ob-
tu be m ovem ent d u ring m echanical ventilation).
stru ction bu t can also resu lt in p ostobstru ctive p u lm onary
ed ema. This is treated by m echanical ventilation w ith PEEP Tracheoesophageal Fistula
and ap p rop riate d iuresis.
The incid ence of this uncom m on bu t highly m orbid com p li-
cation is 0.5% (39). TEF is life-threatening because of con-
■ Late postoperative complications tam ination of the airw ay and interference w ith nu trition.
Long-term com p lications of tracheotom y inclu d e stenosis TEF is com m only associated w ith tracheal stenosis since it
and fistu lae. These p roblem s are typ ically related to d irect shares a com m on p athophysiology. Patients present w ith a
p ressu re necrosis at the cu ff site (36). Initial m u cosal u lcer- d ram atic increase in tracheal secretions, resem bling enteral
ation lead s to cartilage exp osu re, infection, and necrosis. A feed ings. Coughing may follow oral sw allow ing. Gastric
fibrotic strictu re or fu ll-thickness p osterior p erforation d istension m ay occu r second ary to ventilated air into the
into the esop hagu s or anterior p erforation into the innom - stomach. Initial d iagnosis is mad e w ith end oscopy through
inate artery can occu r (19). Tracheostom y tu be cu ffs the stom a and can be confirm ed w ith m ethylene blue d ye
shou ld be kep t betw een 20 and 25 m m H g becau se p res- sw allow and observation of d ye in the trachea. Bariu m
su res above 25 m m H g have been show n to occlu d e su b- sw allow is d iagnostic. If the patient is ventilated , a low -
m u cosal tracheal cap illaries (14). Since the ad vent of high p ressure cuffed end otracheal tube shou ld be ad vanced
volu m e, low -p ressu re cu ffs, and sp ecially d esigned tra- below the fistu la site and a gastrostomy p erformed for gas-
cheotom y tu bes for u nu su al neck anatom y, these com p li- tric d rainage and a jeju nostom y for enteral nutrition (39).
cations have d ecreased . There is evid ence that TEFs d o not close spontaneously (19).
Therefore, m anagem ent is su rgical. Princip les of surgical
Tracheal Stenosis management includ e multilayered repair w ith interposition
This section w ill focu s on tracheal stenosis as it relates to of muscle betw een the esop hagus and trachea.
tracheotom y. The d iagnosis and m anagem ent of tracheal
stenosis follow ing intu bation are d iscu ssed in the section Tracheoinnominate Artery Fistula
on com p lications of intu bation. TIF is a rare, often fatal com plication that occurs w hen a tra-
Fortu nately, tracheal stenosis follow ing tracheotom y is cheostomy tube erod es anteriorly into the posterior w all of
a rare com p lication. One stu d y of 2,000 tracheotom ies the innominate artery. TIF can also occu r as a consequence
d em onstrated the incid ence of tracheal stenosis to be 0.5% of tracheal resection and tracheal stenting. The incid ence is
(37). Technical factors in tracheotom y contribu ting to reported to be 0.3% follow ing tracheotomy, and most occur
betw een 1 and 2 w eeks postoperatively (40). The mortality notom y w ith m ajor vascu lar rep air. Once in the op erating
rate is 75% (41). Survival d epend s on prompt recognition room , m ore d etailed end oscop y u nd er general anesthesia
and management. Prevention, throu gh the use of the fol- can be p erform ed to confirm the d iagnosis.
low ing proced u res, is vital: Bleed ing from a TIF can occur w ithout a recognized sen-
tinel bleed . In this case, im m ed iate bed sid e m anagem ent is
1. Avoid p lacing the tracheostom a too low ; it shou ld id e-
crucial because of the risk of imminent exsanguination.
ally be betw een the second and third tracheal rings.
Tamponad e w ith hyperinflation of the tracheostomy tube
2. Be aw are of a high innom inate artery. Routine intraop er-
cuff is a useful temporizing maneuver. If this fails, the air-
ative p alp ation shou ld be ad vocated for this possibility.
w ay shou ld be controlled w ith an orotracheal tu be from
3. Use a proper sized pliable nonreactive tracheostom y
above and ad vanced d istal to the bleed ing site w hile the tra-
tube, the cu ff p ressu re of w hich w ill not exceed 25 m m
cheostomy tube is removed . Digital pressure through the
H g (14).
stom a against the m anubrium of the sternu m w ill tam pon-
4. Avoid tight closu re of the tracheostom y w ou nd to p re-
ad e the bleed ing source 90% of the time (42). This maneuver
vent local contam ination. Tracheotom y shou ld be p er-
can be performed either through the lumen of the trachea or
form ed throu gh a sm all cu taneou s incision w ithou t
in the pretracheal fascial plane (44). Once the airw ay has
su bsequ ent w ou nd closu re.
been stabilized in this fashion, the p atient should be
5. Use flexible connection tu bing to the ventilator su p-
brou ght rapid ly to the OR for d efinitive management.
p orted by an ad ju stable arm to prevent extraneou s
Definitive su rgical m anagem ent of TIF is obtained via a
m ovem ent and angu lation.
m ed ian sternotom y to achieve p roxim al and d istal control
6. Use a flexible end oscop e (i.e., nasopharyngoscop e or
of the innom inate artery. An u p p er p artial sternotom y that
p ed iatric bronchoscope) to ensu re proper p osition of the
is carried laterally into the right third intercostal sp ace has
tube if p osition is equivocal.
been d escribed to p revent sternal w ou nd contam ination
Abou t 50% of p atients w ith TIF d evelop a sentinel by tracheal secretions (43). The innom inate artery is
bleed —that is, a history of m inor self-lim ited bleed ing exp osed p roxim al and d istal to the TIF. If an aberrant left
prior to p resentation (42). Therefore, the surgeon mu st be carotid artery is fou nd , p roxim al control is obtained d istal
mind fu l of the possibility of TIF in the setting of d elayed to its takeoff. Review of the literatu re reveals that p rim ary
posttracheotom y bleed ing. In the case of a sentinel bleed , rep air of the d am aged artery is not recom m end ed becau se
w e recom m end end oscopy through the tracheostom y tube of the high failu re rate (43). Definitive m anagem ent shou ld
to exam ine the d istal airw ay and then end oscop y throu gh be ind ivid u alized and m ay inclu d e revascu larization or
the stom a d u ring grad u al w ithd raw al of the tracheostom y resection of the fistu lou s segm ent and coverage w ith vas-
tu be over the scop e to m ore carefu lly assess the anterior cu larized om entu m . The read er is d irected to a recent
tracheal w all for erosion. Angiography is not help fu l review for a d iscu ssion of m anagem ent op tions and con-
becau se of tim e constraints and lim ited accu racy (43). If troversies (45).
im m inent TIF is su sp ected , p reparations shou ld be m ad e to
go to the op erating room prom ptly by obtaining large bore Tracheocutaneous Fistula
intravenou s access, cross m atching blood , and consu lting This is an uncom m on com p lication that results from epithe-
su rgical colleagu es cap able of p erform ing m ed ian ster- lialization betw een tracheal mucosa and skin (Fig. 23.4).
A B
FIGURE 23.4. Tracheocutaneous fistula demonstrating epithelialized tract between tracheal mucosa and skin.
N ormally, up on d ecannulation, the tracheostomy w ou nd 3. Postoperative chest x-ray⎯to rule ou t pneum othorax
closes second arily w ithin d ays. Failure of closure results in and p neu m om ed iastinu m
tracheocutaneous fistula and is seen in patients w ith pro- 4. Well-trained p aram ed ical p ersonnel, fam ily, and appro-
longed tracheostom y tube placem ent, poor nu trition, p riate u se of equ ip m ent and m onitors
immu nosu pp ression, rad iation therapy, and local infection. 5. Postoperative surveillance bronchoscopies at regu lar
Clinical m anifestations includ e poor cosm esis, d ifficu lt intervals (i.e., every 6 m onths) or w henever ind icated
phonation, and local skin irritation from secretions. Single- w ith a change in clinical statu s (51)
stage surgical closure has been d escribed w hereby a peris-
tomal circular incision is mad e, creating an epid ermal flap
that is inverted in ord er to line the tracheal surface, and the ■ Percutaneous tracheotomy
external skin is closed prim arily (46). Other authors em pha- The concep t of p ercu taneou s tracheotom y originated in
size the importance of interposing vascularized tissue, such 1969 (52) and has been recently p op u larized (53). Percu ta-
as strap mu scles, betw een the tracheal closure and the over- neou s tracheotom y has gained p op u larity becau se it is a
lying skin (47). bed sid e p roced u re that is relatively brief and inexp ensive
and requ ires no op erating room tim e. There are nu m erou s
Granuloma
techniqu es of p ercu taneou s tracheotom y, inclu d ing p ro-
Granu lation tissu e can occu r anyw here along the tra- gressive d ilational techniqu e, nonp rogressive d ilational
cheostom y tract, com m only on the anterior tracheal w all techniqu e, and translaryngeal tracheotom y (54). These
near the su p erior aspect of the stom a. If granu lation is techniqu es have been d escribed w ith or w ithou t end o-
broad -based and is not causing airw ay obstru ction, obser- scop ic gu id ance. The p roblem of accid ental d ecannu la-
vation is accep table. Med ical m anagem ent w ith meticu lou s tion can be trou blesom e to d eal w ith becau se there is no
stom a care and silver nitrate cau tery is also usefu l. If gran- form al op ening in the trachea; therefore, recannu lation
ulation tissu e is p ed u nculated and causing airw ay com p ro- can be d ifficu lt and reintu bation m ay be necessary. A com -
mise, im m ed iate rem oval w ith cup ped forcep s and p lication u niqu e to this p roced u re is m isgu id ed w ire
cau terization w ith silver nitrate is w arranted . p lacem ent, w hich can be p aratracheal, m ed iastinal, or
su bm u cosal.
A recent m eta-analysis com p ared op en tracheotom y
■ SPECIAL CONSIDERATIONS w ith p ercu taneou s tracheotom y (55). This analysis of ran-
d om ized , controlled stu d ies d em onstrated that although a
■ Pediatric tracheotomy p ercutaneou s tracheotomy is faster and less expensive than
The incid ence of com p lications follow ing tracheotom y in op en tracheotom y, there is a 60% greater likelihood of
the p ed iatric p op u lation is higher than in ad ults. The com - m inor early com p lications w ith the p ercu taneou s tech-
plication rate in the literature varies consid erably, ranging n iqu e (od d s ratio 1.6; 95% con fid en ce interval 1.01–2.66;
from 7.8% to 77% (31). A recent report by Carr et al. p res- p 0.04). With resp ect to major com p lications, ou t of 1,273
ents a d etailed analysis. The au thors fou nd a com p lication p atients analyzed in 14 stu d ies, three of 522 percutaneou s
rate of 11% in the early p ostoperative period (i.e., before the tracheotom ies (0.58%) and one of 628 op en tracheotom ies
first tu be change) and 63% in the late postop erative p eriod (0.16%) resu lted in a p eriop erative d eath (p 0.33).
(i.e., after the first tu be change) (48). In this stu d y, the m ost Althou gh this is not statistically significant, further d ata
common complications were stomal granuloma (26%), tra- are necessary over larger p op u lations of p atients. Further-
cheitis (18%), and asp iration p neu m onia (9%), and seriou s m ore, there are cu rrently a variety of d ifferent percuta-
com p lications w ere tu be obstru ction (9%) and accid ental neou s techniqu es that shou ld be fu rther stu d ied . On the
d ecan nu lation (6%). The in cid ence of trach eal stenosis basis of this literatu re and d irect clinical exp erience, the fol-
rep orted in the literatu re ranges from 1% to 12% (49). The low ing consid erations w ith p ercu taneou s tracheotom y are
reported incidence of pneumothorax and pneumomed i- recom m end ed :
astinum is also quite varied in the literature, ranging from 0%
to 60% (49). The tracheotomy-related mortality rate varies 1. A team app roach betw een su rgeons and critical care
from 0.7% (48) to 6% (50). The reason for the high reported sp ecialists is essential to select the ap p rop riate tra-
rate of complications in children is intuitive—child ren have cheotom y techniqu e for a given p atient.
more p liable soft tissues of the neck, sm aller anatomy, and 2. The p roced u re shou ld be p erform ed by su rgeons cap a-
a tend ency to m ove against a ventilator. Review of the p er- ble of d oing op en tracheotom y.
tinent literatu re id entified the follow ing consid erations 3. End oscop ic gu id ance is obligatory.
w ith p ed iatric tracheotomy (48,50,51): 4. Absolu te contraind ication⎯em ergency airw ay.
5. Relative contraind ications—obesity, enlarged thyroid ,
1. Vertical skin incision—to perm it easier d issection and coagu lop athy, althou gh som e au thors su ggest that this
visu alization is safe in coagulopathic or heparinized patients becau se
2. Gu id e su tu res on the trachea—to perm it safer recannu - sm all vessels are com p ressed rather than transected or
lation in case of accid ental d ecannu lation cau terized (56).
■ Cricothyroidotomy on cricothyroid otom y com p lications. Several stu d ies have

d ocu m ented a high incid ence of voice d istu rbance follow -
In 1921, Chevalier Jackson published a land m ark p ap er ing cricothyroid otom y, ranging from 40% to 75% (60,63,64).
cond em ning cricothyroid otom y (57). H e stated that “high The m echanism involves (i) scarring of the cricothyroid
tracheotom y shou ld never be d one” becau se of the high m em brane, w hich lim its the p ivoting of the thyroid carti-
observed rate of laryngeal stenosis (57). This d octrine lage on the cricoid cartilage that is necessary to increase
rem ain ed u n ch allen ged u n til 1976, w h en Bran tigan an d length and tension of the vocal fold s, and (ii) glottic scar-
Grow p u blished stu d y of a large series of card ioth oracic ring, as a consequ ence of the close p roxim ity (10 m m ) of the
su rgery p atien ts w ho u n d erw en t cricothyroid otom y for true vocal fold s w ith the u pper lim it of the cricothyroid
elective airw ay m an agem en t (58). Cricoth yroid otom y is m em brane (59).
ap p rop riate in th e em ergency airw ay situ ation becau se it In su m m ary, su bglottic stenosis can occu r follow ing
is rap id and can be life-saving. The con troversies are cricothyroid otom y, even in carefu lly selected p atients, and
(i) w hether cricothyroid otom y should be converted to for- vocal d ysfu nction is a com m on com p lication that is d iffi-
mal tracheostomy for long-term airw ay m anagem ent and cu lt to m anage. We conclu d e that (i) cricothyroid otom y is
(ii) whether elective cricothyroidotomy should be performed. ind icated in the em ergency airw ay setting, (ii) em ergency
Jackson review ed 200 cases of chronic laryngeal stenosis cricothyroid otom y shou ld be exp ed itiou sly converted to
and fou nd that 158 cases w ere d ue to “high tracheotomy” a form al tracheotom y in an elective setting in ord er to
(57). N ot all cases w ere true cricothyroid otomies, as most lim it vocal d ysfu nction and p revent su bglottic stenosis,
involved d ivision of the cricoid cartilage and 32 cases w ere and (iii) elective cricothyroid otom y for long-term airw ay
performed through the cricothyroid membrane and thyroid m anagem ent may be ind icated in cases in w hich it is cru cial
cartilage. Many patients had an u nd erlying inflam m atory to m aintain separation betw een the cervical w ou nd and the
disord er of the larynx that m ay have pred isposed them to m ed ian sternotom y w ou nd and is contraind icated in
the d evelopment of stenosis. Jackson reasoned that the sub- p atients w ho have been intu bated for 7 d ays or longer,
glottis is the narrow est segment of the airw ay and that the p atients w ith coexisting laryngeal p athology, occu pational
subglottic mucosa is intolerant to trauma. H e therefore and p rofessional voice u sers, and p atients u nd er the age of
ad vocated “low tracheotomy” below the second tracheal 18 (59).
ring in ord er to prevent laryngeal stenosis. Brantigan and
Grow challenged this d octrine in their review of 655 tho-
racic surgery patients w ho und erw ent elective cricothy-
■ TRACHEAL SURGERY
roid otomy. They observed no cases of chronic subglottic Ind ications for tracheal resection inclu d e p rim ary tracheal
stenosis but found five cases of chronic tracheal stenosis at tu m ors, tu m ors invad ing the trachea, and stenosis. The
the cuff site, all requiring tracheal resection. They cite absence m ost com m on ind ication for tracheal resection and recon-
of cross-contamination of median sternotomy wounds, sim- stru ction is p ostintu bation tracheal stenosis (45); therefore,
plicity, and safety as the basis of their recommend ation that m ost com p lications of tracheal su rgery can be avoid ed by
routine elective cricothyroid otom y is appropriate. H ow - p revention of tracheal stenosis. Prevention is achieved by
ever, follow -up w as lim ited (i.e., obtained in m any cases atrau m atic intu bation techniqu e, p rop er selection of end o-
w ith telephone calls to patients or referring physicians) and tracheal tu be, p rop er inflation of a low -p ressu re cu ff, and
data on vocal qu ality w as lacking. Subsequently, several avoid ance of long-term end otracheal intu bation. H ow -
stud ies d emonstrated variable rates of subglottic stenosis, ever, w hen tracheal resection is ind icated , the su rgeon
ranging from 1% to 48%. A meta-analysis of 875 patients m u st be aw are of p otential ad verse ou tcom es, their m an-
w ho und erw ent cricothyroid otomy revealed a 4% overall agem ent, and their p revention. Tracheal resection and p ri-
incid ence of su bglottic stenosis. The authors d em onstrated m ary anastom osis are highly su ccessfu l. A recent series of
that if patients w ith contraind ications to cricothyroid otomy 23 cases of acqu ired u p p er airw ay stenosis treated w ith
are exclud ed , this incid ence d rops to 1% (59). Contraind ica- segm ental resection and p rim ary reanastom osis had a
tions includ e prolonged end otracheal intubation at 7 d ays d ecannulation rate of 96% (65). The comp lication rate of tra-
or greater (59), coexisting laryngeal infection (57,60), and cheal surgery has been found to increase as the anastomotic
upp er airw ay d ifficulties after end otracheal intu bation. level rises (45).
Other risk factors for subglottic stenosis follow ing elective
cricothyroid otom y inclu d e p rolonged cannulation beyond ■ Intraoperative complications
30 d ays (61) and patients und er the age of 18 (59,62). This
seemingly low incid ence of subglottic stenosis contrasts Recurrent Laryngeal Nerve Injury
w ith a 0.5% incid ence of tracheal stenosis follow ing tra- Given its p roxim ity to the trachea, the RLN is prone to
cheotomy (37). Subglottic stenosis is significantly more d if- inju ry d u ring tracheal su rgery. This is p articu larly tru e in
ficu lt to manage than tracheal stenosis and shou ld therefore the up per cervical trachea and near the laryngotracheal
be prevented w henever possible. ju nction. Meticu lou s su rgical techniqu e and know led ge of
The effect of cricothyroid otom y on voice has been neg- p ertinent anatom y are the m ost im portant safeguard s to
lected in m u ch of the early, nonotolaryngologic literatu re lessen the likelihood of inju ry.
The p rim ary clinical m anifestations of u nilateral RLN p ossible sp ontaneou s recovery, a p eriod of 6 m onths to
inju ry are a p aralyzed vocal fold and d ysphonia (66). Som e 1 year is generally ad vocated .
patients w ill also have d ysphagia and signs of asp iration. Voice therap y by a sp eech p athologist shou ld be consid -
Airw ay com p rom ise, usually w ith strid or d ue to bilateral ered to help am eliorate sym ptom s d u ring a period w hen
vocal fold p aralysis, is the hallm ark of bilateral RLN inju ry. sp ontaneou s recovery is p ossible, in p oor su rgical cand i-
Treatment options for unilateral RLN injury include the d ates, or for p atients w hose sym p tom s are tow ard the less
nonsurgical alternatives of observation or voice therapy. Sur- severe sid e of the sp ectru m . Vocal therap y m ay also be
gical treatment options include vocal fold medialization with em p loyed as an ad ju nctive treatm ent either p reoperatively
injection laryngoplasty or laryngeal framework surgery, or or p ostop eratively in su rgically treated p atients.
laryngeal reinnervation (67). The ideal treatment option, that Although surgical medialization of a paralyzed vocal
is able to restore physiologic movements, is not yet at hand. fold d oes not restore norm al d ynamic laryngeal physiology,
Exp ectant m anagem ent is appropriate in circu m stances it is typically a very effective geometrical solution for incom-
w here the p aralysis m ay be tem porary, such as a neu - plete glottic closure (Fig. 23.5). Med ialization allow s the con-
rapraxia d u e to traction inju ry or w hen the sym p tom sever- tralateral, normal vocal fold to make better contact w ith the
ity d oes not mand ate treatm ent. When observing for paralyzed vocal fold d uring phonation and d eglutition.
FIGURE 23.5. Patient with uni-

lateral vocal fold paralysis due to
right recurrent laryngeal nerve
(RLN) injury during inspiration (A)
and phonation (B) prior to laryn-
geal framework surgery with type-
I thyroplasty. Same patient during
inspiration (C) and phonation (D)
postsurgical medialization of the
paralyzed vocal fold.
A B
C D
Injection laryngop lasty is an end oscop ic techniqu e in Major Hemorrhage

w hich a su bstance is injected into the p aralyzed vocal fold Major hem orrhage d u ring tracheal su rgery is u su ally from
in ord er to ad d bu lk and m ed ialize the free ed ge. A temp o- inju ry to the innom inate artery. It is im p ortant to secure the
rary su bstance, su ch as a Gelfoam (Upjohn, Kalam azoo, airw ay em ergently by p lacem ent of a cu ffed end otracheal
MI), can be u sed to relieve sym ptom s w hen spontaneou s tu be at or d istal to the bleed ing site. Details of management
recovery of m obility is still possible. A w id e variety of other of innom inate artery bleed ing are d iscu ssed in the section
injectable su bstances of longer d u ration are also em p loyed , on com p lications of tracheotom y.
w ith the search for an id eal p ermanent injectable su bstance
continu ing.
Op en laryngeal fram ew ork su rgery is frequ ently u sed ■ Postoperative complications
to treat p atients w ith u nilateral vocal fold paralysis, and Complications follow ing tracheal surgery can be thought of
the m ed ialization thyrop lasty or type-I thyroplasty is the as problems at the site of the anastomosis (i.e., d ehiscence,
m ost com m only em ployed fram ew ork proced ure. This granulation, tracheal stenosis, TIF) and problems that coex-
op eration involves p recise op ening of the thyroid cartilage ist w ith the acquired tracheal stenosis (i.e., tracheom alacia,
lateral to the p aralyzed vocal fold and p lacem ent of an laryngeal d ysfunction). In general, prevention of these com-
approp riate imp lant into the paraglottic space (68). The plications is possible w ith the follow ing consid erations:
proced u re is typ ically perform ed u nd er local anesthesia in
ord er to assess voice w ith varying d egrees of m ed ialization 1. Accurate preop erative assessm ent of laryngeal function
to d eterm ine the optim um geom etry. Options for graft 2. Accurate end oscopic and rad iographic assessm ent of
m aterial inclu d e Silastic, Gore-Tex (W. L. Gore & Associ- the extent of stenosis, tracheal anatom y, and p resence of
ates, Inc., Flagstaff, AZ), and various prefabricated kits. associated tracheomalacia
Efficacy of typ e-I thyrop lasty has been d em onstrated u sing 3. Minim izing tension on the anastom osis; ap p rop riate u se
a variety of ou tcom e m easu res (69,70). of releasing maneu vers
Cu rrently em ployed laryngeal reinnervation tech- 4. Avoid ance of circu m ferential tracheal d issection in
niques, p articu larly the ansa cervicalis to RLN nerve trans- ord er to p reserve blood su p p ly
fer (71), can im p rove voice by restoring bulk and tone to 5. Awareness of predisposing conditions such as mechanical
vocal fold m u scu latu re (72). They d o not, how ever, restore ventilation, prior radiation therapy, immunosuppression,
physiologic m ovem ent. Cu rrent research in laryngeal rein- Wegener granulomatosis, and relapsing polychondritis
nervation inclu d es exp loring the p otential for gene therap y 6. Mu ltid iscip linary ap p roach, inclu d ing otolaryngology,
in the treatm ent of laryngeal paralysis (73,74). thoracic su rgery, and anesthesiology
Managem ent of bilateral RLN inju ry u su ally requ ires 7. Prevention of acqu ired p ostintubation stenosis by atrau-
su rgical intervention to establish an ad equ ate airw ay. m atic intu bation techniqu e, p rop er selection of end otra-
Assu rance of airw ay p atency is d one acu tely by intu ba- cheal tu be, p rop er inflation of low -p ressu re cuff, and
tion follow ed by tracheotom y or by tracheotom y alone. avoid ance of long-term intu bation
Once a stable su rgical airw ay has been established , d eci-
Dehiscence
sions abou t long-term m anagem ent can be m ad e. In the
setting of p ossible tem p orary p aralysis, observation is Excessive tension on the anastomosis can result in dehis-
ap p rop riate. If p erm anent bilateral p aralysis exists, tra- cence. This results from improper mobilization of the trachea
cheotom y can be u sed as th e lon g-term airw ay m anage- or excessive resection. Clinically, acute d ehiscence is mani-
m ent strategy. Alternatively, p roced u res to enhan ce the fested by subcutaneous emphysema. Treatment is emergent,
glottic airw ay, su ch as p osterior cord otom y or ary- consisting of rigid bronchoscopy, re-exploration and repair.
ten oid ectom y, can be p erform ed (75). In form ed consent The repair can be reinforced w ith a local muscle flap.
for these p roced u res m u st inclu d e the know led ge that a Accurate id entification of extent of d isease and prop er
d egree of voice com p rom ise is an exp ected trad e-off for p reop erative p lanning p revents this com p lication. If a long
airw ay im p rovem en t. segm ent of trachea need s to be resected , the su rgeon m u st
be aw are of techniqu es to increase m obilization of the lar-
Superior Laryngeal Nerve Injury ynx and trachea. These inclu d e finger d issection in the p re-
Inju ry to the sensory internal branches of this nerve, p artic- tracheal p lane, su p rahyoid release, infrahyoid release, hilar
ularly a bilateral inju ry, m ay result in d ysp hagia and asp i- release, reim p lantation of left m ainstem bronchus, and
ration. The internal branches of the su perior laryngeal neck flexion (23). In the p ed iatric p op u lation, a novel tech-
nerve (SLN ) enter the larynx via the thyrohyoid m em brane niqu e term ed slid e tracheop lasty has been d escribed to
and are in the su rgical field w hen hyoid releasing m aneu - m anage long-segm ent congenital tracheal stenosis (76).
vers are em p loyed to enhance tracheal reanastom osis.
Inju ry to the external m otor branches of the SLN , w hich Granulation
innervate the cricothyroid m u scles, resu lts in loss of u p p er This is an uncommon complication of tracheal surgery. In a
vocal range. Voice and sw allow ing therapy are the prim ary large series of tracheal resections, five out of 317 cases (1.6%)
treatm ent strategies. d eveloped granulation tissue at the site of the anastomosis
w hen an absorbable suture material w as used (45). When 10. Tyler EP. Complications of anesthesia for otolaryngology⎯head and neck
surgery. In: Weissler MC, Pillsbury HC, ed s. Complications of head and neck
significant granulation occurs, treatment may consist of surgery. New York, NY: Thieme Medical Publishers; 1995:371–388.
antibiotics, local injection of corticosteroids such as triamci- 11. Sataloff RT, Bou gh IB, Sp iegel JR. Arytenoid d islocation: d iagnosis and
nolone, and endoscopic removal. treatm ent. Laryngoscope 1994;104:1353–1361.
12. H offm an H T, Brunberg JA, Winter P, et al. Arytenoid su blu xation: d iag-
Tracheal Stenosis nosis and treatm ent. Ann Otol Rhinol Laryngol 1991;100:1–9.
13. Santos P, Afrassiabi A, Weym u ller EA. Prosp ective stu d ies evalu ating
Prevention consists of ensuring a tension-free anastom osis the stand ard end otracheal tu be and a prototype end otracheal tube.
Ann Otol Rhinol Laryngol 1989;98:935–940.
and com p lete rem oval of all inflam ed tissue ad jacent to the 14. H effner JE, H ess D. Tracheotom y m anagem ent in the chronically venti-
stenotic segm ent. Method s of tracheal release are d iscu ssed lated patient. Clin Chest Med 2001;22(1):55–69.
in the section on d ehiscence. Managem ent of tracheal 15. Stauffer JL, Olson DE, Petty TL. Com p lications and consequ ences of
end otracheal intu bation and tracheotom y: a p rosp ective stu d y of 150
stenosis is d iscu ssed in the section on com p lications of critically ill ad u lt p atients. Am J Med 1981;70:65–76.
intu bation. 16. Grillo H C. Treatm ent of airw ay com p lications. Appl Cardiopulm Patho-
physiol 1989(3):147–159.
Tracheoinnominate Artery Fistula 17. Bogd asarian RS, Olson N R. Posterior glottic laryngeal stenosis. Oto-
laryngol Head Neck Surg 1980;88:765–772.
This rare, d read ed com p lication is d iscussed in the section 18. H ogikyan N D. Transnasal end oscop ic exam ination of the su bglottis
on com p lications of tracheotom y. Pred isposing factors fol- and trachea u sing top ical anesthesia in the otolaryngology clinic.
Laryngoscope 1999;109:1170–1173.
low ing tracheal su rgery includ e the presence of a d ehiscent 19. Wood DE, Mathisen DJ. Late com p lications of tracheotom y. Clin Chest
anastom otic su tu re line ad jacent to the innom inate artery, Med 1991;12(3):597–609.
presence of a low tracheotom y, or local infection. Interp osi- 20. Gold enberg AN . End oscop ic p ostcricoid ad vancem ent flap for p oste-
rior glottic stenosis. Laryngoscope 2000;110:482–485.
tion of viable tissue (i.e., strap m uscle, thym u s, p eri- 21. Rahbar R, Shapshay SM, H ealy GB. Mitom ycin: effects on laryngeal
card iu m , or om entu m ) betw een the anastom otic su tu re line and tracheal stenosis, benefits, and com p lications. Ann Otol Rhinol
and the innom inate artery is recomm end ed (43). Laryngol 2001;110:1–6.
22. Wain JC. Postintu bation tracheal stenosis. Chest Surg Clin N Orth Am
Tracheomalacia 2003;13:231–246.
23. H eitm iller RF. Tracheal release m aneu vers. Chest Surg Clin N Orth Am
Tracheom alacia that exists p reop eratively shou ld be id en- 2003;13:201–210.
24. Kou fm an JA. The otolaryngologic m anifestations of gastroesop hageal
tified at the tim e of end oscop y and shou ld be inclu d ed in reflu x d isease (GERD): a clinical investigation of 225 p atients u sing
the resected tracheal segm ent. If tracheom alacia d evelop s am bu latory 24-hour pH m onitoring and an exp erim ental investigation
follow ing tracheal su rgery, treatm ent op tions inclu d e of the role of acid and p ep sin in the d evelop m ent of laryngeal inju ry.
Laryngoscope 1991;101:1–64.
reresection of the d iseased trachea or exteriorization of 25. H offm an H T, Overholt E, Karnell M, et al. Vocal p rocess granu lom as.
the airw ay and stenting w ith a tracheostom y tu be or a Head Neck 2001;23:1061–1074.
T-tu be (45). 26. N asri S, Sercarz JA, McAlp in T, et al. Treatm ent of vocal fold granu -
lom a using botu linu m toxin typ e A. Laryngoscope 1995;105(6): 585–588.
Chronic Aspiration 27. Berke GS. Voice d isord er and p honosu rgery. In: Bailey BJ, Calhou n KH ,
ed s. Head and neck surgery—otolaryngology, 2nd ed . Philad elp hia, PA:
This m ay occu r as a resu lt of u nrecognized coexisting Lipp incott–Raven Pu blishers; 1998:767–780.
28. Le BT, Eyre JM, H olm gren EP, et al. A tracheostom y com p lication
laryngeal d ysfu nction, RLN injury, or laryngeal releasing resulting from acquired tracheom alacia: case rep ort. J Trauma 2001;50:
m aneu vers. Coexistin g laryngeal d ysfu nction m u st be 120–123.
corrected initially, if possible, before tracheal su rgery is 29. Ow en RL, Cheney FW. End obronchial intu bation: a p reventable com -
p lication. Anesthesiology 1987;67:255–257.
attem p ted . 30. Briacom be J, H olyoake L, Keller C, et al. Pharyngolaryngeal, neck, and
jaw d iscom fort after anesthesia w ith the face m ask and laryngeal m ask
airw ay at high and low cu ff volu m es in m ales and fem ales. Anesthesiol-
■ REFERENCES ogy 2000;93(1):23–31.
31. Gold enberg D, Ari EG, Golz A, et al. Tracheotom y com p lications: a ret-
1. H effner JE. The role of tracheotom y in w eaning. Chest 2001;120(6): rosp ective stud y of 1130 cases. Otolaryngol Head Neck Surg 2000;123:
477S–481S. 495–500.
2. McCu lloch TM, Bishop MJ. Com p lications of translaryngeal intu ba- 32. Rogers ML, N ickalls RWD, Brackenbu ry ET, et al. Airw ay fire d u ring
tion. Clin Chest Med 1991;12(3):507–521. tracheostom y: prevention strategies for surgeons and anaesthetists.
3. Loh KS, Irish JC. Trau m atic com p lications of intu bation and other air- Ann R Coll Surg Engl 2001;83:376–380.
w ay m anagem ent p roced u res. Anesthesiol Clin North Am 2002;20(4): 33. N g J, H artigan PM. Airw ay fire d u ring tracheostom y: shou ld w e extu -
953–969. bate? Anesthesiology 2003;98(5):1303.
4. Coe TR, H u m an M. The p eri-op erative com p lications of nasal intu ba- 34. Malata CM, Foo IT, Sim p son KH , et al. An au d it of Björk flap tra-
tion: a com p arison of nostril sid e. Anaesthesia 2001;56(5):447–484. cheostom ies in head and neck p lastic su rgery. Br J Oral Maxillofac Surg
5. Weym u ller EA, Bishop MJ. Problem s associated w ith p rolonged intu - 1996;34(1):42–46.
bation in the geriatric p atient. Otolaryngol Clin North Am 1990;23: 35. Berg LF, Mafee MF, Cam p os M. Mechanism s of p neu m othorax follow -
1057–1074. ing tracheal intubation. Ann Otol Rhinol Laryngol 1988;97:500–505.
6. Schultz-Cou lon H J. Rep air of p ostintu bational lesions of the cartilagi- 36. And rew s MJ, Pearson FG. The incid ence and p athogenesis of tracheal
nou s nose in infants⎯som etim es a su rgical p roblem . Int J Pediatr injury follow ing cu ffed tube tracheostom y w ith assisted ventilation:
Otorhinolaryngol 1984;7(2):119–131. analysis of a tw o-year prosp ective stu d y. Ann Surg 1971;173:249–263.
7. Pettett G, Merenstein GB. N asal erosion w ith nasotracheal intu bation 37. Chew JY, Cantrell RW. Tracheostom y. Arch Otolaryngol Head Neck Surg
[letter]. J Pediatr 1975;87(1):149–150. 1972;96:538–545.
8. Lockhart P, Feld bau EV, Gabel RA. Dental com p lications d u ring and 38. Fry TL, Jones RO, Fischer N D, et al. Com p arisons of tracheostom y inci-
after tracheal intu bation. J Am Dent Assoc 1986;112:480–483. sions in a ped iatric m od el. Ann Otol Rhinol Laryngol 1985;94:450–453.
9. Weym u ller EA. Prevention and m anagem ent of intu bation injury of the 39. Reed MF, Mathisen DJ. Tracheoesop hageal fistu la. Chest Surg Clin N
larynx and trachea. Am J Otolaryngol 1992;13:139–144. Orth Am 2003;13:271–289.
40. Grillo HC, Donahue DM, Mathisen DJ, et al. Postintubation tracheal 59. Bu rkey B, Esclam ad o R, Morganroth M. The role of cricothyroid otom y
stenosis: treatment and results. J Thorac Cardiovasc Surg 1995;109:486–493. in airw ay m anagem ent. Clin Chest Med 1991;12(3): 561–571.
41. Grillo HC, Mathisen DJ. Cervical exenteration. Ann Thorac Surg 1990;49: 60. Cole RR, Agu ilar EA. Cricothyroid otom y versu s tracheotom y: an oto-
401–408. laryngologist’s p ersp ective. Laryngoscope 1988;98:131–135.
42. Jones JW, Reynold s M, H ew itt RL, et al. Tracheo-innom inate artery ero- 61. Ku riloff DB, Setzen M, Portnoy W, et al. Laryngotracheal inju ry follow -
sion: su ccessfu l su rgical m anagem ent of a d evastating com p lication. ing cricothyroid otom y. Laryngoscope 1989;99:125–130.
Ann Surg 1976;184:194–204. 62. Sise MJ, Shackford SR, Cru ickshank JC, et al. Cricothyroid otom y for
43. Allan JS, Wright C. Tracheoinnom inate fistu la: d iagnosis and m anage- long-term tracheal access: a prospective analysis of m orbid ity and m or-
m ent. Chest Surg Clin N Orth Am 2003;13:331–341. tality in 76 p atients. Ann Surg 1984;200(1):13–17.
44. Utley JR, Singer MM, Roe BB, et al. Definitive m anagem ent of innom i- 63. Gleeson MJ, Pearson FG, Arm istead S, et al. Voice changes follow ing
nate artery hem orrhage com p licating tracheostom y. JAMA 1972;220: cricothyroid otom y. J Laryngol Otol 1984;98:1015–1019.
577–579. 64. H olst M, H ertegard S, Persson A. Vocal d ysfu nction follow ing cricothy-
45. Lanu ti M, Mathisen DJ. Managem ent of com p lications of tracheal su r- roid otom y: a p rosp ective stu d y. Laryngoscope 1990;100:749–755.
gery. Chest Surg Clin N Orth Am 2003;13:385–397. 65. Wolf M, Shap ira Y, Talm i YP, et al. Laryngotracheal anastom osis: p ri-
46. Law son DW, Grillo H C. Closu re of p ersistent tracheal stom as. Surg m ary and revised p roced u res. Laryngoscope 2001;111:622–627.
Gynecol Obstet 1970;130:995–996. 66. H off PT, H ogikyan N D. Unilateral vocal fold p aralysis. Curr Opin Oto-
47. Bishop JB, Bostw ick J, N ahai F. Persistent tracheostom y stom a. Am J laryngol Head Neck Surg 1996;4:176–181.
Surg 1980;140:709–710. 67. Zeitels SM, Casiano RR, Gard ner GM, et al. Managem ent of com m on
48. Carr MM, Poje CP, Kingston L, et al. Com p lications in p ed iatric tra- voice problem s: com m ittee rep ort. Otolaryngol Head Neck Surg 2002;126:
cheostom ies. Laryngoscope 2001;111:1925–1928. 333–348.
49. Krem er B, Botos-Krem er A, Eckel H E, et al. Ind ications, com p lications 68. Isshiki N , Morita H , Okam u ra H , et al. Thyrop lasty as a new p honosu r-
and surgical techniqu es for p ed iatric tracheostom ies—an u pd ate. J gical technique. Acta Otolaryngol (Stockh) 1974;78:451–457.
Pediatr Surg 2002;37:1556–1562. 69. Lu nd y D, Casiano RR, Xu e JW, et al. Thyrop lasty typ e I: short versu s
50. Rod gers BM, Rooks JJ, Talbert JL. Ped iatric tracheostom y: long-term long-term resu lts. Otolaryngol Head Neck Surg 2000;122: 533–536.
evalu ation. J Pediatr Surg 1979;14(14):258–263. 70. H ogikyan N D, Wod chis WP, Terrell JE, et al. Voice-related qu ality of life
51. Carron JD, Derkay CS, Strop e GL, et al. Ped iatric tracheotom ies: chang- (V-RQOL) follow ing type I thyroplasty for unilateral vocal fold paraly-
ing ind ications and ou tcom es. Laryngoscope 2000;110: 1099–1104. sis. J Voice 2000;14:378–386.
52. Toye FJ, Weinstein JD. A p ercu taneou s tracheotom y d evice. Surgery 71. Cru m ley RL. Upd ate: ansa cervicalis to recu rrent laryngeal nerve anas-
1969;65:384–389. tom oses for u nilateral laryngeal p aralysis. Laryngoscope 1991;101:
53. Ciaglia P, Firsching R, Syniec C. Elective p ercu taneou s d ilatational tra- 384–387.
cheostom y: a new sim p le bed sid e p roced u re: prelim inary rep ort. Chest 72. Olson D, God ing GS, Michael DD. Acou stic and p ercep tu al evalu ation
1985;87:715–719. of laryngeal reinnervation by ansa cervicalis. Laryngoscope 1998;108:
54. Sharpe MD, Parnes LS, Drover JW. Translaryngeal tracheostom y: exp e- 1767–1772.
rience of 340 cases. Laryngoscope 2003;113(3):530–536. 73. Flint PW, Shiotani A, O’Malley BW. IGF-I gene transfer into denervated
55. Oliver ER, Gist A, Gillesp ie MB. Percu tan eou s versu s su rgical rat laryngeal muscle. Arch Otolaryngol Head Neck Surg 1999;125:274–279.
tracheotom y: an u p d ated m eta-analysis. Laryngoscope 2007;117(9): 74. Ru bin AD, Mobley B, H ogikyan N D, et al. Delivery of an ad enoviral
1570–5. vector to the cru shed recurrent laryngeal nerve. Laryngoscope 2003;113:
56. And erson H L, Bartlett RH . Elective tracheotomy for m echanical ventila- 985–989.
tion by the p ercu taneous technique. Clin Chest Med 1991;12(3):555–560. 75. H illel AD, Benninger M, Blitzer A, et al. Evalu ation and m anagem ent
57. Jackson C. H igh tracheotom y and other errors—the chief cau ses of of bilateral vocal cord im m obility. Otolaryngol Head Neck Surg 1999;121:
chronic laryngeal stenosis. Surg Gynecol Obstet 1921;32:392–398. 760–765.
58. Brantigan CO, Grow JB. Cricothyroid otom y: elective u se in resp iratory 76. Cu nningham M, Eavey RD, Vlahakes GJ, et al. Slid e tracheop lasty for
p roblem s requ iring tracheotom y. J Thorac Cardiovasc Surg 1976;71: long-segm ent tracheal stenosis. Arch Otolaryngol Head Neck Surg 1998;
72–80. 124(1):98–103.
CHAPTER
24
Complications of Esophageal Surgery

Andrew C. Chang and Mark D. Iannettoni
■ ANATOMIC AND PHYSIOLOGIC cervical d ysphagia and aspiration p neu m onia (1). Sim i-
larly, inju ry to the vagal nerve tru nks in op erations on the
CONSIDERATIONS
d istal esop hagu s m ay p rod u ce neu rogenic d ysp hagia or
Many of the com p lications of esop hageal su rgery are gastric atony and pylorospasm , w hich are very trou ble-
related d irectly to the u niqu e featu res of esop hageal some complications after esophageal surgery.
anatom y and p hysiology. Detailed know led ge and thor- Physiologic consid erations influ ence other com p lica-
ou gh u nd erstand ing of these characteristics are essential tions follow ing su rgery of the esop hagu s. The pathophysi-
for the su rgeon to id entify potential p itfalls of esophageal ology of gastroesop hageal reflu x and second ary reflu x
surgery and avert com plications before they occu r. A esop hagitis d irectly influ ences the results of antireflu x sur-
uniqu e feature of esophageal anatom y is its u nu su ally fatty gery and hence the com p lication of recu rrent reflu x. For
subm u cosa, w hich allow s greater m obility of the overlying exam p le, it has been d em onstrated that the incid ence of
squ am ou s mu cosa. In perform ing a m anual esop hageal recu rrent reflu x in p atients u nd ergoing the stand ard
anastomosis, every suture shou ld transfix the m u cosal Belsey Mark IV tran sth oracic h iatal h ern ia rep air in the
ed ge, w hich at tim es can retract m ore than 1 cm from the p resence of esop h agitis or a strictu re is betw een 25% and
cu t esop hageal m argin (Fig. 24.1). The esophagu s is also 75% (2,3). In the p resen ce of the in tram u ral inflam m ation
uniqu e in the gastrointestinal tract because it lacks a serosal an d esop hageal sh ortening that m ay accom p an y reflu x
layer. The soft and often tenuou s m u scle hold s su tu res esop h agitis, th e esop hageal su tu res of th e Belsey rep air
poorly and cannot be relied u pon to m aintain a fu nd op lica- m ay not be reliable, an d tension on the rep air to red u ce
tion, for exam p le, unless the associated su bm u cosa is the requ isite 3 to 5 cm of d istal esop hagu s below the
includ ed by the esophageal stitch. d iap hragm sets the stage for recu rrence of th e hern ia
The esophagu s is nourished by four to six paired aortic- (Fig. 24.2). These sam e consid erations ap p ly to the N issen
esophageal arteries as w ell as collateral circu lation from the fu n d op lication and the H ill p osterior gastropexy, w hich
inferior thyroid , intercostals, bronchial, inferior phrenic, also aim to restore an intra-abd om inal segment of d istal
and left gastric arteries. Althou gh the segmental “poor” esop hagu s and require esophageal or periesop hageal
blood su pp ly of the esophagu s has frequently been incrimi- su tu res. To avert the com p lication of d isru ption of the
nated as the cau se of anastom otic d isru ption, the su bm u - rep air d u e to the need to su tu re inflam ed esop hagu s and
cosal collateral circulation of the esophagus is extensive. tension on the rep air, the esop hagu s-lengthening Collis
Even after the card ia has been d ivid ed and the intrathoracic gastrop lasty can be com bined w ith a fu nd op lication (4–6).
esophagu s m obilized completely out of the chest, the d istal The gastrop lasty tu be fu nctions as a new d istal esop hagu s
end of the esophagu s m aintains good arterial bleed ing so and p rovid es healthy, resilient tissu e, i.e., the gastric w all,
long as the inferior thyroid arteries rem ain intact. Poor tech- arou nd w hich to p erform the fu nd op lication. Fu rtherm ore,
nique, not p oor blood sup ply, is the m ore likely exp lanation the ad d itional “esop hageal length” p rovid ed by the gastro-
for the complication of esophageal anastomotic d isruption. p lasty tu be red u ces tension on the rep air (Fig. 24.3). The
Finally, parasym pathetic innervation of the esophagus is p resence of reflu x esop hagitis and a p ep tic strictu re also
supplied by the vagus nerves, and the recurrent laryngeal com p licates an antireflu x p roced u re if the strictu re is p erfo-
supplies the upper portion of the esophagus. Recurrent rated d u ring attem p ted d ilation.
laryngeal nerve inju ry d u ring esophageal su rgery can resu lt An intrathoracic esophagogastric anastomotic leak, per-
in one of the m ost d evastating com p lications, cricopharyn- haps the m ost d read ed com p lication of esophageal su rgery,
geal m u scle d ysfunction w ith subsequent incapacitating ow es its morbid ity in part to associated gastroesophageal
reflu x. An intrathoracic esop hagogastric anastom osis is
Andrew C. Chang: University of Michigan Med ical Center, associated alm ost invariably w ith the d evelop m ent of
Ann Arbor, MI 48109. reflu x esop hagitis, com p ared w ith a cervical esop hagogas-
Mark D. Iannettoni: University of Iow a H ospitals and tric anastom osis, w hich is rarely associated w ith clinically
Clinics, Iow a City, IA 52242. significant reflu x. Althou gh it has been argu ed that w ith
257
FIGURE 24.1. Misplacement of the esopha-

gogastric anastomotic suture. The relatively
great mobility of the esophageal mucosa over the
fatty submucosa permits the cut mucosal edge to Esophagus
retract proximally. Unless care is taken to identify
the mucosa and properly transfix it with each
suture, mucosal apposition will not occur and an
anastomotic disruption will follow. (Reproduced Retracted
with permission from Orringer MB. Complications mucosa
of esophageal surgery and trauma. In: Greenfield
LJ , ed. Complications in surgery and trauma, 2nd
ed. Philadelphia, PA: J .B. Lippincott; 1990:303.)
'04
RF
H
Misplaced sutures Correctly placed sutures
ap prop riate attention to d etail, an intrathoracic esopha-

gogastric anastom osis can be performed reliably and w ith
an exceed ingly low morbid ity rate (7), the potential for an
anastomotic leak and second ary med iastinitis cannot be
eliminated totally, and this fact perhaps more than anything
else has influenced our current “d efensive posture” that the
best esophagogastric anastomosis is a cervical anastomosis,
w ith w hich the consequence of a leak is a salivary fistula
and not life-threatening med iastinitis and sep sis.
Gastroesop hageal reflu x after esop hageal resection and
an esop hagogastric anastom osis m ay be resp onsible for
life-threatening asp iration of gastric contents into the tra-
cheobronchial tree in the early p ostop erative p eriod . For
this reason, initial d ecom p ression of the intrathoracic stom -
ach w ith a nasogastric tu be and p lacem ent of the p atient in
a 45 head -u p p osition are im p ortant. Sim ilarly, because of
the potential for regu rgitation and asp iration after eating,
p atients w ho have a fresh esop hagogastric anastom osis
should not be perm itted to u nd ergo postural d rainage as
p art of their p ostop erative p u lmonary p hysiotherapy
w ithin 1 to 2 hou rs of m ealtim e.
The p otential p u lm onary com p lications, p rim arily asp i-
ration p neu m onia, resu lting from esop hageal obstruction
d u e to a variety of cau ses cannot be overestim ated . Particu-
larly in the p atient w ith a m egaesop hagu s of ad vanced
achalasia, the risk of m assive regu rgitation and aspiration
on ind u ction of general anesthesia is enormou s. Aw areness
of this p ossibility d ictates the need for nasogastric tube
esophageal d ecom pression and em ptying in these patients
before a rapid sequ ence ind uction of general anesthesia
and end otracheal intu bation.
FIGURE 24.2. A sliding hiatus hernia with a peptic stricture at the esopha-
gogastric junction (arrow). Standard antireflux operation (Hill, Belsey, or Nis-
sen) require reduction below the diaphragm not only of the esophagogastric
■ ESOPHAGEAL PERFORATION
junction but also the distal 3 to 5 cm of esophagus. The relative shortening Perforation of the thoracic esop hagu s, w ith resu ltant med i-
associated with the distal esophagitis in this patient prevented a tension-free
astinitis, p oses a d evastating threat. Regard less of the cau se
standard repair. (Reproduced with permission from Orringer MB. Complica-
tions of esophageal surgery and trauma. In: Greenfield LJ , ed. Complications of p erforation (Table 24.1), d elay in recognition and d efini-
in surgery and trauma, 2nd ed. Philadelphia, PA: J .B. Lippincott; 1990:305.) tive m anagem ent increases concomitant m ortality and
Chapter 24 • Complications of Esophageal Surgery 259
Table 2 4 . 1 Ca u ses of esop h a gea l p er fora t ion geal area m ost com m only inju red (Fig. 24.4). Perforation
of th e m id and d istal esop h agu s is m ost likely to occu r
Instrumental follow in g biop sy or d ilatation (Fig. 24.5). There has been
Endoscopy
increasing aw areness of esop hageal necrosis and atrioe-
Direct injury
sop hageal fistu la d u e to therm al inju ry su stained d u ring
Transesophageal echocardiography
Injury occurring during removal of a foreign body catheter-based rad iofrequ ency ablation for atrial fibrilla-
Dilatation tion, w ith incid ence ranging from 0.03% to 0.5% and p os-
Intubation (esophageal, endotracheal) sibly higher (11). Sp ontaneou s p erforation u su ally occu rs
Catheter-based radiofrequency ablation for atrial fibrillation follow in g strainin g (Boerhaave’s synd rom e) w ith ru p -
Noninstrumental tu re involving the left p osterior asp ect of the d istal
Barogenic trauma esop hagu s (12).
Postemetic
Blunt chest or abdominal trauma
Other (e.g., labor, convulsion, defecation) ■ DIAGNOSIS
Penetrating neck, chest or abdominal trauma
Patients w ith esop hageal p erforation typ ically p resent
Postoperative
Anastomotic disruption
w ith p ain, d irectly referrin g to th e site of p erforation. Th e
Devascularization following pulmonary resection, vagotomy or p resence of m ed iastin al air or hyd rop n eu m othorax on
repair of hiatal hernia chest rad iograp h in a p atient su sp ected of having a p er-
Injury following ingestion of caustic agent foration is confirm atory. H ow ever, a norm al ch est rad i-
Erosion by adjacent infection with resultant fistula involving the ograp h d oes not exclu d e the p ossibility of esop hageal
tracheobronchial tree, pericardium, pleural cavity or aorta p erforation. N ot every esop h ageal tear is a fu ll-thickn ess
Pathologic d isru p tion . For exam p le, p neu m atic d ilatation of th e
Severe reflux esophagitis esop hagu s for achalasia m ay resu lt in a tear of the d istal
Candidal, herpetic and opportunistic infection esop hageal m u cosa and su bm u cosa. Air insu fflation
throu gh a flexible esop hagoscop e m ay resu lt in m ed iasti-
nal, cervical or su bcu tan eou s air, exaggeratin g th e exten t
of inju ry. Follow ing esop hagoscop y or esop hageal op era-
m orbid ity. Rep air of an acute esophageal tear in an other- tion, p ostop erative p ain or fever shou ld be consid ered a
w ise norm al esop hagu s w ithin 6 to 8 hou rs carries a risk of resu lt of esop hageal p erforation u ntil p roven otherw ise.
m orbid ity that 1is essentially the sam e as that im p osed by Contrast esop hagogram shou ld be p erform ed im m ed i-
elective esop hagotom y and prim ary esop hageal closu re. If ately in ord er to lim it any fu rth er d elay in establish ing
op erative intervention is d elayed beyond this early p eriod , p rop er d rainage and / or d efinitive rep air. Water-solu ble
local inflam m ation greatly jeopard izes prim ary healing of contrast esop hagogram , follow ed by d ilu te bariu m , best
the esop hageal tear and mortality rises d ram atically (8–10). id entifies the site of p erforation (Fig. 24.6), w hether the
Esop hageal instru m entation accou nts for the large p erforation com m u nicates w ith either the p leu ral or p eri-
m ajority of iatrogenic p erforation, w ith the cricop h aryn - toneal cavities, or is confined to th e m ed iastinu m .
FIGURE 24.3. A: This lateral view from a preoperative esopha-

gogram show a large, sliding hiatus hernia with half of the stomach
above the left hemidiaphragm (arrow), a proximal stricture, and
esophageal dilatation from the obstruction. B: Postoperative appear-
ance of the reconstructed distal esophagus following intraoperative
dilatation of the stricture and a Collis gastroplasty-Nissen fundopli-
cation. The horizontal gastric folds in the fundoplication around the
distal 5 to 7 cm of the functional esophagus can be seen. Also visible
are the titanium clips (small arrow) marking the diaphragmatic hiatus
and those at the new esophagogastric junction (large arrow). There
is no evidence of esophageal stenosis, and the dilation proximal to
the obstruction has resolved. (Reproduced with permission from
Orringer MB. Complications of esophageal surgery and trauma. In:
Greenfield LJ, ed. Complications in surgery and trauma, 2nd ed.
Philadelphia; PA. J.B. Lippincott; 1990:308.)
A B
FIGURE 24.4. The mechanism of endoscopic

cervical esophageal perforation. In performing
rigid esophagoscopy, it is essential that a gentle,
steady, lifting force (arrow) be exerted to displace
forward the larynx and cricoid cartilage. Failure to
overcome the natural pull of the upper esophageal
sphincter against the cricoid cartilage results in a
typical posterior perforation (inset). (Reproduced
with permission from Orringer MB. Complications
of esophageal surgery and trauma. In: Greenfield
LJ , ed. Complications in surgery and trauma, 2nd
ed. Philadelphia, PA. J .B. Lippincott; 1990:309.)
Cricoid cartilage
Perforation
■ TREATMENT
On ce the d iagn osis of esop h ageal p erforation is estab-
lished , oral intake by the p atient shou ld cease. Aggres-
sive intravenou s flu id resu scitation, facilitated by u sing
eith er a cen tral venou s p ressu re catheter or p u lm on ary
artery catheter, is ind icated if there is hyp ovolem ia asso-
ciated w ith intrathoracic p erforation. Broad -sp ectru m
antibiotic coverage is initiated . The p resence of cariou s
teeth increases the m orbid ity risk of esop hageal inju ry
ow ing to the virulence of sw allow ed oral bacteria. Thus,
oral hygiene cannot be neglected in the p atient w ith an
esop hageal p erforation.
There is controversy about the best m ethod of treatm ent
of p atients w ith esop hageal p erforations. N onoperative
“conservative” therap y is su ccessfu l in som e p atients w ith
esop hageal p erforation, p rim arily those w ith p re-existing
p eriesop hageal and m ed iastinal fibrosis that contains the
inju ry. Thus, for the esophageal d isruption in w hich contrast
material extend s only a few millimeters from the esophageal
lumen and the patient is d oing w ell clinically, antibiotic
therapy, chest tube d rainage as indicated and observation
may suffice (13–15). More frequently, successful outcom e
follow ing esophageal perforation requires surgical interven-
tion (Fig. 24.7).
FIGURE 24.5. Esophageal perforation during an attempt at blind passage of
a dilator through a tight stricture. (Left) The dilator has curled proximal to the Perforation of the cervical and u pper thoracic esopha-
stenosis, and as the bougie is advanced, disruption of the esophagus may gu s is app roached through an oblique cervical incision that
occur. (Right) Using a special-order, large esophagoscope that will accommo- p arallels the anterior bord er of the left sternocleid om as-
date up to a 50-French dilator, the stricture can be visualized directly for
dilatation. (Reproduced with permission from Orringer MB. Complications
toid m u scle. The sternocleid om astoid m u scle and carotid
of esophageal surgery and trauma. In: Greenfield LJ , ed. Complications in sheath are retracted laterally, and the trachea and thyroid
Surgery and Trauma, 2nd ed. Philadelphia, PA. J .B. Lippincott; 1990:310.) gland m ed ially. If the p erforation can be id entified , it is
FIGURE 24.6. Posteroanterior (left) and lateral (center) views

from Gastrografin (meglumine diatrizoate) esophagogram in a
patient with acute caustic injury that was incorrectly dilated
prematurely within 10 days of caustic ingestion. There was still
acute inflammation in this esophagus, and the patient had fever
and chest pain following dilation. Despite the negative Gastro-
grafin swallow, dilute barium was administered (right), and a
perforation (arrow) of the midesophagus was demonstrated.
(Reproduced with permission from Orringer MB. Complications
of esophageal surgery and trauma. In: Greenfield LJ, ed. Com-
plications in surgery and trauma, 2nd ed. Philadelphia, PA: J .B.
Lippincott; 1990:312.)
closed w ith absorbable p olyglycolic acid su tu res. If the w ith su ch a cervical ap p roach. Mid thoracic esop hageal
inju ry cannot be visu alized ad equ ately for rep air, the p erforations m u st be ap p roached throu gh a right thoraco-
retroesop hageal p revertebral sp ace is d issected blu ntly tom y and those of the d istal third of the esop hagu s are
w ith the finger and the su p erior m ed iastinu m is d rained ap p roached throu gh a left thoracotom y.
w ith tw o 1-inch Penrose d rains brou ght ou t throu gh the Trad itional su rgical d ogm a teaches that esop hageal
neck w ou nd . Esop hageal p erforations to the level of the p erforations beyond 6 to 12 hou rs in d u ration are virtu -
tracheal bifu rcation can generally be treated su ccessfu l ally im p ossible to rep air p rim arily, the p ou ting inflam ed
m u cosa at the ed ge of the tear hold ing su tu res p oorly.
Isolated rep orts, how ever, have em p hasized that even
after m arked d elay in rep air, su ccessfu l closu re of the
esop h ageal inju ry m ay be p ossible (8,16). Several grou p s
Signs and symptoms of
h ave fou n d that the m ajority of esop hageal tears can in
esophageal perforation
fact be rep aired su ccessfu lly u sing m eticu lou s su rgical
tech niqu e th at in clu d es id entification of ad jacent su bm u -
Chest radiograph cosa by d issecting aw ay th e overlying m u scle, d efinin g
Contrast esophagogram the lim its of th e m u cosal tear (Fig. 24.8), reap p roxim ation
of the d isru p ted m u cosa and su bm u cosa w ith a su rgical
stap ler (Au to Su tu re End o-GIA II Stap ler, U.S. Su rgical
Walled-off perforation Free perforation
Minimal symptoms Corp oration, Au to Su tu re Com p any Division, N orw alk,
No sepsis CT) (17), and reap p roxim ation of the m u scle over the sta-
p le su tu re line (Fig. 24.9). The esop hageal rep air shou ld
Operative
be p erform ed w ith an esop hageal bou gie in p lace, to lim it
No underlying Resectable malignancy
management disorder Megaesophagus excessive narrow in g of th e lu m en . Lim ited esop hagom y-
Dilatable stricture otom y p erform ed 180 op p osite th e site of in ju ry m ay
Caustic ingestion
p erm it en ou gh ad vancem en t of ad jacent esop hageal w all
for ad equ ate rep air of the p erforation (18). In p atients
Primary repair Primary repair
w ith ch ron ic m ed iastin itis an d p leu ral reaction, the ad ja-
cent m ed iastinal p leu ra is thickened and p rovid es an
FAILURE excellent flap w ith w h ich to reinforce the esop h ageal
Esophageal dilatation
su tu re line. Alternatively, if there is not su fficient p arietal
p leu ral thickening to p rovid e ad equ ate su p p ort for the
su tu re line, reinforcem ent w ith either a p ed icled inter-
Exclusion and diversion Resection costal m u scle flap , om entu m , p ericard iu m , visceral p leu ra,
Anterior thoracic Immediate or
esophagostomy delayed reconstruction or d iap hragm can be carried ou t (19,20). The m ed iastinal
Jejunostomy and delayed p leu ra m u st be op ened from the ap ex of the chest to the
reconstruction d iap hragm to p erm it w id e d rainage of the m ed iastinu m .
FIGURE 24.7. Treatment algorithm for esophageal perforation. After cop iou s irrigation of the m ed iastinu m an d p leu ral
FIGURE 24.8. Technique of primary repair of

esophageal perforation. Mucosa at the site of the
tear (inset) is grasped with Allis clamps (A), and
the adjacent esophageal muscle is mobilized
around the entire tear until 1 cm of normal sub-
Extent of
mucosa is exposed around the defect (B). (Repro- mucosal tear
duced with permission from Whyte RI, Iannettoni
MD, Orringer MB. Intrathoracic perforation: the Normal
merit of primary repair. J Thorac Cardiovasc Surg submucosa
1995;109:140–146.) “Pouting”
mucosa 1 cm mucosa
mobilized
Extent of
Dilator mucosal tear
A B
cavity and d ecortication of an y acu te fibrinou s exu d ate In this subset of patients, consideration should be given for
that m ay h ave form ed over th e lu ng, a large-bore ch est p rim ary esop hagectom y, if their p hysiologic statu s at the
tu be is left near the esop h ageal su tu re line so th at if d is- tim e of op eration p erm its (21). Alternatively, if it is p ossible
ru p tion occu rs, the resu lt w ill be an esop hagop leu ral to d ilate a benign strictu re intraoperatively to relieve the
cu taneou s fistu la. d istal obstru ction, closu re of a p roxim al esop hageal perfo-
In treating an esophageal perforation, associated ration may be successful. A subsequent d isruption of the
esophageal pathology cannot be ignored . Thus, a perfora- esophageal closure may still eventually heal if dilation of the
tion proximal to a carcinoma or a caustic or reflux stricture associated stricture is continued. A perforated pulsion d iver-
may necessitate an emergent esophagectomy w ith either pri- ticulum of the esophagus may be resected w ithin several
mary or d elayed esophageal reconstruction. Patients w ho hours of the injury. The associated obstruction must be d ealt
present w ith esophageal perforation and a long-stand ing w ith and the neuromotor esophageal d ysfunction responsi-
history of reflux stricture are more likely to develop postop- ble for formation of the pouch relieved by performing a con-
erative d ysphagia requiring repeated esophageal d ilatation. comitant esophagomyotomy.
FIGURE 24.9. Technique of primary repair of

esophageal perforation. Traction sutures placed
along the inflamed mucosal edge of the tear
elevate the submucosa so that an EndoGIA-II
cartridge can be applied and deployed. The
Staple
esophageal lumen is maintained by passage of an
intraesophageal dilator (A) (inset). The staple line
is covered by approximating the adjacent muscle
Dilator
with a running absorbable suture (B). (Reproduced
with permission from Whyte RI, Iannettoni MD,
Orringer MB. Intrathoracic perforation: the merit
of primary repair. J Thorac Cardiovasc Surg 1995;
109:140–146.)
Staple line
Intraesophageal
dilator
A B
■ PROCEDURAL COMPLICATIONS encountered approximately 25 cm from the upper inci-

sors. An ep ip hrenic d iverticu lu m located proxim al to
■ Esophagoscopy the esophagogastric junction is encountered before the
esophagoscope reaches a point 40 cm from the upper inci-
Technologic advances in the development of flexible
sors. Perforation of a cervical esophageal d iverticulum or
fiberoptic instruments have greatly facilitated the perform-
a mid esophageal stricture cannot be justified because the
ance of esophagogastroscopy, particularly with the advent
endoscopist w as unaw are of these lesions as a prior bar-
of end oscopic ultrasound . Furthermore, there has been a
ium sw allow examination had been neither obtained nor
concomitant increase in the num ber of these stud ies being
personally reviewed.
performed on an outpatient basis. The consequences of
3. Failure to introduce the rigid esophagoscope properly
esophageal d isruption, how ever, have not changed. Perfora-
through the upper esophageal sphincter may result in a
tion occurs in as many as 0.8% of all patients d uring flexible
perforation. The cricopharyngeus muscle originates from
upper endoscopy, w ith rates as high as 4% for those patients
the cricoid cartilage, and the natural “pull” of this muscle
undergoing esophageal dilatation (22). Perforation follow-
against the cartilage will result in a posterior perforation
ing rigid esophagoscopy can occur in as many as 5% of
unless the larynx is “lifted ” anteriorly as the esophago-
patients follow ing therapeutic proced u res (e.g., biop sy,
scope is ad vanced .
dilation, or rem oval of foreign body) and 1.5% of patients
4. The esop hagoscop e shou ld not be ad vanced unless the
follow ing rigid esophagoscopy alone (23).
lu m en is visible.
1. Ad equ ate p reoperative and intraoperative sed ation and 5. As the esop hagoscop e is ad vanced , ad ju stm ent m u st be
anesthesia are m and atory. In some patients, general m ad e for the natu ral cou rse of the esop hagus. Becau se
anesthesia is the only m eans of creating acceptable con- the d istal esop hagu s cou rses anteriorly and to the left as
d itions for p erform ance of esop hagoscop y for both the it joins the stom ach, p articu larly w hen p erform ing rigid
p atient and the su rgeon. end oscop y, the instru m ent m u st be angled tow ard the
2. Esophagoscopy should not be carried out unless a prior right sid e of the p atient’s m ou th and the occip u t of the
barium esophagogram has been performed and review ed head low ered as the esop hagoscop e is ad vanced into
by the end oscopist, particularly if the patient presents the d istal esophagu s.
w ith symptoms of d ysphagia or esophageal obstruction. 6. The initial dilatation of a tight esophageal stricture is fre-
The barium sw allow provides information about pre- quently painful, and patients must be adequately sedated
existing pathology and its expected location. For exam- and anesthetized, minimizing patient discomfort and
ple, a Zenker d iverticulum identified w ith contrast allow ing the surgeon to concentrate on the visual field.
esophagogram should be expected to be encountered at When a rigid esophagoscope is used for this initial evalua-
the level of the upper esophageal sphincter, approxi- tion, flexible gum-tipped Jackson bougies are inserted
mately 15 cm from the upper incisors. A mid esophageal through the stricture und er direct vision, and the pliability
carcinom a at the level of the tracheal bifurcation is and extent of the stenosis are assessed (Fig. 24.10). With a
FIGURE 24.10. The instruments required

for evaluating an esophageal stricture. Pre-
cisely measured localization of the stricture
(in centimeters from the incisor teeth) and
adequate biopsies and brushings from the
stricture must be obtained. The gum-tipped
Jackson dilators, gently manipulated through
the stenosis, permit evaluation of the extent
and pliability of the obstruction. The 26-
French dilator is the largest one that will pass
through the standard 45-cm rigid esophago-
scope. (Reproduced with permission from
Orringer MB. Complications of esophageal
surgery and trauma. In: Greenfield LJ, ed.
Complications in surgery and trauma, 2nd ed.
Philadelphia, PA: J.B. Lippincott; 1990:309.)
FIGURE 24.11. Tapered Hurst-Maloney

esophageal dilators and a 45-cm Pilling
esophagoscope, which accommodates up to
a 50-French bougie, thus permitting progres-
sive dilatation of severe peptic strictures
under direct vision. (Reproduced with permis-
sion from Orringer, MB. Complications of
esophageal surgery and trauma. In: Green-
field LJ , ed. Complications in surgery and
trauma, 2nd ed. Philadelphia, PA: J .B. Lippin-
cott; 1990:311.)
mild “soft” stenosis, dilation by advancing the esophago- antireflu x op eration, u nless the involved tissu es are rela-
scope through the stenosis might be possible. With more tively healthy and am enable to rep air, esop hageal resection
firm, high-grade strictures, it is safer to pass progressively is generally a better op tion. Althou gh m ost reflu x stric-
larger d ilators through the narrowing. This can be accom- tu res can be d ilated , and m any regress after an antireflu x
plished u sing the Savary-Gilliard gu id ew ire and d ilat-
ing system , w ith flu oroscop ic guid ance, or w ith the
Maloney tap ered esophageal d ilators (Fig. 24.11). The Table 2 4 .2 Com p lica t ion s of h ia t a l
latter instrum ents are ou r preference for repeated ou tpa- h er n ior r h a p hy
tient d ilatations of esophageal strictures, requiring none Intraoperative Complications
of the sedation or anesthesia necessary when endoscopic Perforation
balloon dilatations are performed. Vagus nerve injury
Hemorrhage
Splenic laceration
■ Hiatal hernia repair Short gastric vessel
H iatal herniorrhaphy, although concep tually quite sim p le, Postoperative Complications
can resu lt in a num ber of serious complications (Table 24.2). Perforation
Acute esophageal p erforation can occu r w hen concom itant Stricture
esophagoscop y is perform ed d uring an antireflu x op eration Suture placement
or w hen a d istal esophageal stricture is d isrupted d uring Dysphagia
intraop erative d ilatation. A d elayed perforation, usually Mechanical
w ithin 1 w eek of surgery, can occur w hen esophageal Tight hiatal closure
Excessive fundoplication
sutures placed too d eeply d uring the repair result in local
Inadequate gastroplasty
mural necrosis.
Edema
Acute esophageal tears recognized before the incision Gastric atony, pylorospasm
should be approached transthoracically and repaired , and Early anatomic recurrence
the esophageal suture line reinforced w ith either the fund o- Crural repair disruption
plication if the tear is in the distal esophagus, or with pedi- Functional
cled anterior med iastinal fat or a ped icled intercostal muscle Postvagotomy diarrhea
flap for a more proximal tear. When an intercostal muscle Ileus
pedicle is used to reinforce an esophageal suture line, it Cardiac tamponade
should be sutured to the esophagus as an onlay patch, not Chylothorax
placed circumferentially around the esophagus; regenera- Pleural effusion
Incisional pain
tion of bone or cartilage from the perichond rium or perios-
teum mobilized w ith the flap may result in a late obstructing Modified from Patel HJ, Tan BT, Yee J, et al. A twenty-five year experience with
ring around the esophagus. When a reflux stricture is perfo- open primary transthoracic repair of paraesophageal hiatal hernia. J Thorac
rated d uring attempted d ilation at the time of a planned Cardiovasc Surg 2004;127:843–849.
p rocedure has been carried out, disruption of a stricture dur- m anip u lation of the vagu s nerves at the level of the d istal
ing attempted dilation is one of the definitions of an “undi- esop hagu s. This comp lication after antireflu x su rgery is
latable” stricture that justifies esophageal resection. Our m ore likely w ith a transthoracic than w ith a transabd om i-
preference in this situation is to proceed with a transthoracic nal rep air becau se id entification and d isp lacem ent of the
esophagectomy and then reposition the patient supine and m ain vagal tru nks are more rou tine w ith the former
carry out a cervical esophagogastric anastomosis. Several ap p roach. Su ch p atients have d ysp hagia im m ed iately after
additional options for the treatment of a disrupted distal the antireflu x p roced u re. On bariu m sw allow exam ination,
stricture are available. Unfortunately, none is w ithout its the d istal esop hagu s is tap ered and em p ties p oorly, resem -
associated morbidity. The Thal fundic patch esophagoplasty bling the p ictu re of achalasia or esop hageal spasm . Reas-
utilizes adjacent gastric fundus to “patch” the opened nar- su rance and m aintenance of a soft d iet for several d ays
row ed esophagus. This procedure not only relies on the u su ally constitu te ad equ ate therap y, althou gh passage of
healing of the opened, inflamed distal esophagus to w hich an esop hageal d ilator is at tim es requ ired for relief. This
the stom ach is sutured but also requires the ad d ition of an p roblem typ ically su bsid es sp ontaneou sly, bu t occasionally
intrathoracic fund oplication (Thal-Wood ward proced ure) to reop eration, taked ow n of the rep air, and at tim es, even
control gastroesophageal reflux, in effect, creation of a man- esophageal resection may be need ed .
mad e paraesophageal hiatal hernia. The incid ence of suture Another complication of intraoperative vagus nerve
line disruption and mechanical complications associated injury occurring during a hiatal hernia repair is impaired gas-
w ith this operation cond emn its use. For the same reason, w e tric motility or pylorospasm resulting in delayed gastric emp-
oppose use of an intrathoracic fund oplication (w ithout a tying and second ary gastric dilation. This complication has
Thal proced ure) to control reflux. The complications of such direct implications for the long-term success of the hiatal her-
an approach outw eigh its benefits. nia repair because sustained gastric dilation in combination
Gastric u lceration m ay com p licate 3% to 10% of fu nd o- w ith a competent d istal esophageal sphincter mechanism
p lications and m ay occu r both in su p rad iap hragm atic may eventually result in disruption of the esophageal sutures
fu nd ic w rap s and in intra-abd om inal fu nd op lications. In used to construct the fundoplication and failure of the repair.
the form er, one is d ealing w ith a com p lication of an iatro- When the patient who has undergone an antireflux operation
genic p araesop hageal hiatal hernia, and op erative rep air is develops gastric dilation immed iately after operation, a 7- to
generally ind icated . In the latter, u lceration m ay be d u e to 10-day trial of gastric decompression w ith a nasogastric tube
relative ischem ia in the w rap , and treatm ent w ith H 2- is indicated. At times, an anticholinergic (e.g., atropine 0.4 mg
recep tor blockers, p roton p u m p inhibitors, or cytop rotec- either per os or intramuscularly every 4 to 6 hours) may
tive agents m ay su ffice. The d evelop m ent of fever, chest relieve the associated pylorospasm. This problem should not
p ain, or resp iratory d istress d u ring the first w eek after a be permitted to persist indefinitely, and it is best to perform
hiatal hernia op eration m and ates a contrast stu d y. If a d is- an early gastric drainage procedure (pyloromyotomy or
tal esop hageal p erforation is d iagnosed , treatm ent u su ally pyloroplasty) than to risk recurrent gastroesophageal reflux.
involves reop eration. The site of the p erforation is id enti- Finally, vagal nerve injury may result in varying degrees of
fied intraop eratively, at tim es by insu fflating air throu gh a “d umping syndrome” (e.g., postprandial d iarrhea, cramp-
nasogastric tu be. A leak from an intra-abd om inal fu nd o- ing, abdominal pain, nausea, diaphoresis, palpitations). This
p lication su tu re m ay be closed and reinforced w ith ad ja- problem generally subsides within a few months, but at
cent om entu m . If the leak is in the chest, p ed icled anterior times long-term management w ith antidiarrheal medication
m ed iastinal fat, intercostal m u scle, or p leu ra is u sed to and dietary restriction may be required .
reinforce the closu re u sing a transthoracic ap p roach. A Chylothorax follow ing an antireflu x p roced u re m ay
jeju nostom y feed ing tu be shou ld be p laced to allow nu tri- resu lt from inju ry to the thoracic d u ct, w hich p asses from
tional su p p ort and u nim p ed ed am bu lation in case the the abd om en through the aortic hiatus and then cou rses in
rep air is u nsu ccessfu l and an esop hageal fistu la ensu es. the low er chest anterior to the spine betw een the esopha-
Either a large-bore chest tu be shou ld be left near the tho- gu s and the aorta. Inju ry m ay occu r d u ring m obilization of
racic esop hageal rep air or a d rain shou ld be p laced near the card ia or d u ring p lacem ent of the cru ral su tu res. This
the transabd om inally rep aired fu nd op lication to ensu re com p lication is herald ed by p rolonged chest tu be d rainage
external d rainage of a recu rrent fistu la. after a transthoracic rep air, and the tru e cau se of this
Low retrosternal d ysp hagia after an antireflu x op era- serosangu ineou s d rainage m ay not becom e ap p arent u ntil
tion m ay have one of several cau ses: (a) d istal esop hageal the p atient’s d iet is liberalized and its fat content increases.
ed em a after in traop erative m an ip u lation; (b) d istal If chylothorax is p resent, the oral ad m inistration of 60 to
esophageal m otor d ysfu nction d u e to m anipu lation of the 90 m L of cream for 4 to 6 hou rs w ill cau se the chest tu be
vagu s nerves; (c) obstruction d u e to too tight a fu nd op lica- d rainage to becom e op alescent and m ilky chyle. The d iag-
tion; (d ) or obstruction from excessive closu re of the hiatus. nosis can also be establish ed by stainin g the flu id w ith
Perform ance of the fund op lication over at least a 54 French Su d an R, w hich stains the globu les of fat. Determ ination
intraesophageal d ilator m inim izes the likelihood of this lat- of the ch olesterol and triglycerid e levels in th e flu id is
ter com p lication. Dysphagia after tru ncal vagotom y has u su ally not necessary. A cholesterol/ triglycerid e ratio of
been recognized for m ore than 40 years, and it is ap p arent less than 1 is characteristic of a chylou s effu sion, w hereas
that neurom otor esophageal d ysfu nction m ay follow n onchylou s effu sion s h ave a ratio of greater than 1. In
m ost cases, a ch ylothorax follow ing a hiatal hernia rep air

can be m anaged nonoperatively by ad m inistering a low -
resid u e elem ental d iet and m aintaining p rolonged chest
tu be su ction. If the outpu t of chyle remains significant
( 400 to 600 m L p er consecutive 8-hour period s) after 7 to
10 d ays of this treatm ent, then reoperation w ith id entifica-
tion and ligation of the injured thoracic d uct is ind icated .
Acu te p ostoperative hem orrhage after an antireflux
operation is most often the result of bleed ing from an unse-
cured d ivid ed short gastric vessel along the high greater
curvature of the stomach. This possibility should alw ays be
borne in mind as the short gastric vessels are d ivid ed and
ligated before perform ing a fu nd oplication. H em orrhage
from these vessels may be a particularly treacherous com-
plication follow ing a transthoracic hiatal hernia repair
because the resulting hypovolemic shock may be attribu ted
to other causes (e.g., myocard ial infarction) w hen there is
minimal chest tube d rainage and the chest roentgenogram
show s no hemothorax. Abd ominal exploration, evacu ation
of the blood , and ligation of the bleed ing vessel is the proper
course of therapy. Splenic injury also occurs in a small per-
centage of p atients u nd ergoing antireflux surgery, particu -
larly in reoperations. The incid ence of splenic inju ry is
slightly higher w ith transabd ominal as compared w ith
transthoracic antireflux operations, particularly in obese
patients. Rarely, p ostoperative hemorrhage m anifests as a FIGURE 24.12. An esophagogram taken 1 week after a combined Collis
gastroplasty-Nissen fundoplication. A portion of the fundoplication (arrow) has
pericard ial effusion causing tamponad e and card iop ul- slipped into the chest through the diaphragmatic hiatus because of disruption
monary collapse (24). This may arise by avulsion of an epi- of the posterior crural sutures. Although this patient was asymptomatic, reop-
card ial vessel occurring d uring esophageal mobilization for eration and reduction of the herniated fundus below the diaphragm were car-
ried out to prevent the potential complications of this “paraesophageal”
repair of a large hiatal hernia. Rapid d iagnosis by surface hernia. (Reproduced with permission from Orringer, MB. Complications of
echocard iogram follow ed by sternotom y, relief of tam pon- esophageal surgery and trauma. In: Greenfield LJ , ed. Complications in sur-
ad e, and repair of the bleed ing vessel is ind icated (25). gery and trauma, 2nd ed. Philadelphia, PA: J .B. Lippincott; 1990:316.)
Before the p atient’s d ischarge from the hosp ital after
an antireflu x op eration, a rou tine bariu m sw allow exam i-
nation shou ld be p erform ed to d ocu m ent the p ostop era- recovering from an antireflu x op eration that reop eration
tive ap p earance of the reconstru cted esop hagogastric is necessary, bu t conservative m anagem ent of this p rob-
ju nction. At tim es, this contrast stu d y m ay reveal a lem is ill-ad vised .
“silent” localized extravasation of contrast m aterial at the Controversy rem ains regard ing the role of su rgical
site of one of the fu nd op lication su tu res that w as p laced therap y for p atients w ith com p lications of gastroe-
too d eep ly. If the p atient is asym p tom atic and the “leak” sop hageal reflu x d isease, p articu larly Barrett’s esop hagu s.
is very sm all, no therap y m ay be requ ired becau se the Both sym p tom s and requ irem ent for antisecretory m ed ica-
su p p orting fu nd op lication has p revented a m ore m ajor tions d ecrease significantly follow ing antireflu x op eration
d isru p tion. A far m ore d isconcerting rad iograp hic find ing (26). H ow ever, no long-term d ata are available regard ing
on the “rou tine” p ostop erative bariu m sw allow obtained regression of Barrett’s esop hagu s, regard ed as a p recu rsor
p rior to d ischarge is the asym p tom atic m igration of the lesion to esop hageal ad enocarcinom a. Cu rrently, p atients
fu nd op lication or gastric fu nd u s into the chest as a resu lt w ith Barrett’s esop hagu s u nd ergoing hiatal herniorrhap hy
of d isru p tion of the p osterior cru ral rep air (Fig. 24.12). shou ld continu e rou tine su rveillance esop hagoscop y w ith
This iatrogenic p araesop h ageal hiatal h ern ia is su bject to biop sies in ord er to screen for the p rogression from m eta-
the sam e m echanical com p lications of p araesop hageal p lasia to d ysp lasia and esop hageal ad enocarcinom a (27).
herniation in th e p atien t w ho has had n o su rgery. Reop er-
ation is necessary to red u ce the fu nd op lication back in to
the abd om en and to rep lace the p osterior cru ral su tu res if
■ Laparoscopic antireflux/hiatal hernia surgery
they have p u lled throu gh the cru ral m u scle (or to narrow Since 1991, w hen the first rep orts of lap aroscop ic antire-
the hiatu s fu rther if they have not), before p ostop erative flu x su rgery w ere p u blished , m inim ally-invasive su rgical
ad hesion s form betw een the h erniated stom ach an d ad ja- ap p roaches to the d iap hragm atic esop hageal hiatu s have
cent tissu es, m aking any su bsequ ent rep air m ore d iffi- been u sed w ith increasing frequ ency. Althou gh m ortality
cu lt. It m ay be d ifficu lt to tell the asym p tom atic p atient rates for lap aroscop ic fu nd op lication have been low (0% to
1.4%), early morbidity rates were acceptable, and conversion most large combined slid ing and paraesophageal hiatal her-
rates to the open proced ure w ere from 0% to 14%, so the nias should be approached through the chest w ith an open
learning curve for this operation is substantial (28,29). operation, generally a combined Collis gastroplasty and Nis-
As operator experience increases, laparoscop ic antire- sen fundoplication. The increasing number of fundoplica-
flu x op erations or hiatal hernia repairs can be accomplished tions that have “slipped ” through the hiatus into the chest
safely in obese patients, those w ith intra-abd ominal ad he- after laparoscopic repair likely reflect, at least in part, a lack
sions from prior surgery, or in those w ith an unusually large of recognition by the original surgeon that there was unac-
left hep atic lobe. These factors rem ain ind ications for open ceptable tension on the repair. Recurrent herniation of an
transthoracic hiatal hernia repair. Perforations of the d istal intact or a partially d isrupted fund oplication is the m ost
esophagu s or gastric fund u s have been reported d u ring common reason for failure of laparoscopic fund oplications.
laparoscopic fund oplication. Blind d issection posterior to Bod y habitus is another important but often overlooked fac-
the esophagus should be avoid ed to prevent this complica- tor in recurrence after laparoscopic (or any) antireflux opera-
tion. When recognized at the time of, or soon after operation; obesity is present in a significant number of patients
tion, laparoscopic repair is feasible, but repair may also w ho experience disruption of repairs.
w arrant conversion to an open proced ure. Another laparoscopic technique for the repair of p arae-
Early postoperative dysphagia may result from an overly sophageal hiatal hernias is the u se of prosthetic m esh to
tight fund oplication, w hich is more likely to occur w ith min- rep air the d iap hragm atic d efect. This is an ill-conceived
imally invasive proced ures in which tactile sensation is not op eration becau se the constant d iap hragm atic m otion
used to assess the tightness of the w rap. Performance of the against the ad jacent esop hagu s at the hiatu s m ay result in
fund oplication over at least a size 54 French Maloney d ilator esop hageal or gastric erosion and p erforation (33) as late as
minimizes the likelihood of this complication. Postoperative 9 years follow ing op eration (34). This ap p roach is m en-
d ysp hagia d u e to fibrotic stenosis of the m u scu lar tioned only to cond em n its use.
esophageal hiatus, attributed to a diathermy injury during
the esophageal dissection, has also been reported and treated ■ Esophageal resection and visceral
with laparoscopic hiatal division. Persistent dysphagia after a
esophageal substitution
laparoscopic fund oplication, refractory to dilatation therapy,
may necessitate reoperation, takedow n of the wrap, and con- In almost every large series of patients undergoing a tradi-
struction of a looser fundoplication. The author ’s approach tional esophageal resection and substitution w ith either
for such reoperative procedures is a transthoracic approach, stomach or intestine, the leading causes of d eath are (a) res-
generally with a combined esophageal lengthening Collis piratory insu fficiency associated w ith the p hysiologic
gastroplasty and Nissen fundoplication. Additional compli- insu lt of a com bined thoracic and abd om inal op eration
cations of laparoscopic fundoplication include pneumotho- and (b) sep sis from m ed iastinitis resu lting from d isru p tion
rax or pneumomediastinum from CO 2 tracking into the chest of an intrathoracic anastom osis. As a resu lt, ou r grou p has
during the operation, incisional hernia at a port site, and her- ad op ted a general p olicy of p erform ing no intrathoracic
niation of the fundoplication through the diaphragmatic hia- esop hageal anastom oses and p refers a cervical esop ha-
tus (particularly w hen the crura were not closed at the time of gogastric anastomosis instead . A cervical esophagogastric
the original operation). anastomotic leak generally represents little more morbid ity
As enthusiasm for laparoscopic fundoplication has than a salivary fistula, and spontaneous closure w ith local
grow n, this approach has also been used to repair large w ound care is the rule. The authors and associates reported
paraesophageal hiatal hernias, w hich are often associated a d ramatic red uction in the incid ence of postoperative cervi-
w ith an attenuated , abnormally wide esophageal hiatus. In cal esophagogastric anastomotic leak to less than 3% with a
1983, Pearson et al. emphasized that esophageal shortening side-to-side stapled cervical esophagogastric anastomosis
is common in these patients, most of w hom have combined (35) constructed with the Auto Suture Endo-GIA II Stapler
sliding and paraesophageal hiatus hernias, and the authors (U.S. Surgical Corporation, Auto Suture Company Division,
used the combined Collis gastroplasty-fund oplication oper- N orw alk, CT). The authors have also found that a transhiatal
ation liberally in this group (30,31). With the laparoscopic esophagectomy w ithout thoracotomy and a cervical esopha-
approach, one cannot assess the d egree of tension on the d is- gogastric anastomosis is applicable in most patients requir-
tal esophagus that results from reduction of the esopha- ing esophageal resection and reconstruction for both benign
gogastric junction below the diaphragm, because, again, and malignant d isease. This proced ure minimizes the opera-
d irect manual palpation of the esophagus is not possible. tive insult to the patient by avoiding a thoracotomy. The inci-
Furthermore, w ith the diaphragm pushed abnormally d ence of postoperative pulmonary complications is thereby
upw ard by CO 2 insufflation of the abdomen, a false sense of reduced , and the possibility of mediastinitis resulting from
ease of red uction of the esophagogastric junction into the an intrathoracic leak is virtually eliminated .
abdomen may occur. Although several groups have devel- The au thors recom m end a N o. 14 French ru bber
oped minimally-invasive techniques for combined Collis catheter feed ing jeju nostom y tu be secu red in p lace w ith a
gastroplasty and fund oplication, w ith acceptable early and Witzel m aneu ver, not a “need le catheter” jeju nostom y, in
intermed iate-term results (29,32), our group believes that every p atient u nd ergoing esop hagectom y and esop hageal
reconstruction. The jejunostomy tube is regard ed as an rep air. Decom p ression of the esop hageal su bstitu te w ith a
“insurance policy” if anastomotic disruption necessitates an nasogastric tu be, p lacem ent of a jeju nostom y tu be for
alternate means of nourishment. If use of the tube is not nu tritional su p p ort, and ap p rop riate antibiotics com p lete
required postoperatively, it is removed after several w eeks. the therap y. Follow ing rem oval of the chest tu bes, a bar-
Alternatively, if an anastomotic leak occurs, a feeding iu m sw allow exam ination shou ld be p erform ed 10 d ays
jejunostomy tube is safer and more effective in provid ing follow ing reoperation to be certain that healing has
calories than intravenous hyperalimentation. occu rred . If d isru p tion of the anastomosis recu rs, a con-
trolled esop hagop leu ral cu taneou s fistu la shou ld be estab-
lished . Rib resection w ith p lacem ent of a large-bore
■ Anastomotic leak d rainage tu be ad jacent to the fistu la m ay be requ ired to
After completion of a cervical esophageal anastomosis, the ensure that all d rainage from the esophageal leak can flow
neck w ound is closed loosely w ith only four or five 4-0 freely ou t of the chest. Gastric contents that are aspirated
sutures over a 1/ 4-in Penrose d rain placed ad jacent to the throu gh the nasogastric tu be can be retu rned to the alim en-
anastomosis. If an anastomotic leak does occur, the neck tary tract throu gh the jeju nostom y tu be to m inim ize elec-
w ound is opened at the bed sid e in its entirety, and gentle trolyte im balance and to sim p lify flu id and electrolyte
w ound packing w ith gauze is initiated . The size of the leak rep lacem ent.
can be estimated by having the patient d rink w ater and eval- Du ring re-exp loration of the chest for a d isru p ted
uating the amount that escapes from the neck wound with a esop hageal anastom osis, extensive local necrosis of the
disposable bed sid e suction catheter. In general, within sev- tissu e w ith a m ajor anastom otic d ehiscence m and ates
eral days of opening the w ound, the drainage diminishes reversal of the anastom osis, resection of nonviable stom -
consid erably, and the patient may resume oral intake w hile ach, and rep lacem ent of the rem aining stom ach into the
maintaining stead y gentle pressure over the w ound to abd om en. Only nonviable d istal esop hagu s shou ld be
occlud e the fistula. Passage of tapered Maloney d ilators resected . H ow ever, a d iverting lateral cervical esop hagos-
(generally, N os. 40 and 46 French) at the bed sid e d uring the tom y w ith oversew ing of the d ivid ed p roxim al intratho-
first w eek after d rainage of the cervical fistula ensures that racic esop hagu s shou ld not be attem p ted . Disru p tion of
no element of obstruction from either local edema or spasm the intrathoracic esop hageal su tu re line is not only likely,
contributes to continued d rainage of the fistula (36). More bu t if su bsequ ent reconstru ction is p ossible, m anagem ent
than 98% of cervical esophagogastric anastomotic leaks are of the rem aining segm ent of intrathoracic esop hagu s
small and respond to the open d rainage and packing as p resents a consid erable technical p roblem . The best alter-
described . A small proportion, how ever, are associated w ith native is to m obilize the esop hagu s circu m ferentially w ell
catastrophic complications: major gastric tip necrosis neces- into the neck throu gh the thoracic incision. After the tho-
sitating taked ow n of the anastomosis, construction of cervi- racotom y is closed , form al end esop hagostom y, w ith the
cal esophagostomy and resection of nonviable stom ach, p atient retu rned to the su p ine p osition, shou ld be p er-
vertebral bod y osteomyelitis, epidural abscess w ith result- form ed . As ind icated earlier, the su bm u cosal collateral
ant paraplegia, pulmonary microabscesses from an internal circu lation of the esop hagu s is excellent, and m ost of the
jugular vein abscess, and tracheoesophagogastric anasto- length of the thoracic esop hagu s w ill rem ain viable so
motic fistula (37). long as at least one inferior thyroid artery rem ains intact.
Early d isru p tion of an intrathoracic esop hageal anas- Therefore, after d elivering the d ivid ed thoracic esop ha-
tom osis occu rring w ithin the first 10 critical d ays after gu s ou t of the neck incision, the m axim u m length of
op eration is characterized by the signs and symptoms of rem aining esop hagu s shou ld be p reserved to facilitate
med iastinitis. Symptoms, includ ing fever, chest pain, tachy- later reconstru ction. This is achieved by d evelop ing a su b-
card ia, tachypnea, respiratory d istress, peripheral cyanosis, cu taneou s tu nnel anteriorly to the left clavicle onto the
vasoconstriction, hypotension, and shock, w hen associated chest w all, in ord er to constru ct an anterior thoracic
w ith a chest roentgenogram that d emonstrates hyd rothorax esop hagostom y. An esop hagostom y stom a p laced on the
or pneumothorax, leave little question about the d iagnosis. relatively flat u p p er anterior chest w all is m u ch m ore eas-
Diagnosis should be d ocumented w ith a contrast stud y. In ily cared for by the p atient becau se a stom al ap p liance is
an otherwise asymptomatic patient found to have a small m ore read ily ad ap ted to this location than to the u su al
( 1 cm) contained anastomotic leak on a rou tine postopera- site of a stand ard cervical esop hagostom y (Fig. 24.13). A
tive bariu m sw allow, observation alone m ay be su fficient. feed ing jeju nostom y is, of cou rse, requ ired u ntil later
In m ost cases, how ever, anastom otic d isru ption w arrants esop hageal reconstru ction can be p erform ed .
im m ed iate re-exp loration, irrigation of the chest and m ed i- When colon or jeju nu m has been u sed to rep lace the
astinum , rep air of the fistu la, if possible, and chest tu be esop hagu s and necrosis of the graft is d ocum ented at re-
d rainage. A localized anastom otic leak w ith viable ad jacent exp loration for an anastom otic leak, there is sim ilarly little
tissu e m ay be am enable to d irect su tu re repair. A p ed icled recou rse bu t to rem ove the nonviable graft and insert a
flap of anterior m ed iastinal fat, intercostal mu scle flap , feed ing tu be. If the p atient su rvives the sequ elae of the
pleu ra, or om entu m should be m obilized to reinforce the m ed iastinal sep sis, later reconstru ction can be consid ered .
m aintain a satisfactory lu m en and to p revent late high-

grad e stenosis. A cervical fistu la generally heals w ithin 7
to 10 d ays of external d rainage. When the p atient retu rns
for follow -u p w ithin 2 w eeks of d ischarge, a N o. 46
French or larger Maloney d ilator is p assed throu gh the
anastom osis. If the p atient has no d ysp hagia and there is
no resistance to p assage of the d ilator, the need for su bse-
qu ent d ilatations is d ictated by the retu rn of cervical d ys-
p hagia. In p atients w ith anastom otic narrow ing that
p revents the free p assage of a N o. 46 French or larger Mal-
oney d ilator, a m ore aggressive p rogram of esop hageal
B d ilatation is u nd ertaken. With an early p rogram of w eekly
d ilatations, anastom otic healing in a p atent configu ration
hrf'04 is often achieved . Patients w hose anastom otic strictu re
p rod u ces resistance as the d ilator is p assed m ay need
m ore frequ ent d ilatations. In this situ ation, over several
A w eeks, the p atient is tau ght to p ass a N o. 46 or 48 French
FIGURE 24.13. Construction of an anterior thoracic esophagostomy d ilator w ith the assistance of a fam ily m em ber or friend .
instead of a traditional end-cervical esophagostomy. A: The mobilized tho- Once facility w ith p assage of the d ilator is achieved , the
racic esophagus is placed on the anterior chest wall so that the location of the
p atient is issu ed a d ilator w ith instru ctions to p ass it d aily
stoma can be determined. B: All viable remaining esophagus is preserved and
tunneled subcutaneously, and an end anterior thoracic esophagostomy is for 1 w eek, then every other d ay for 1 w eek, and then at
constructed. Stomal appliances are readily applied to the flat surface of the increasingly longer intervals u ntil the longest d u ration
anterior chest, and when performing a later colon interposition, 7 to 12 cm of betw een d ilatations w ithou t the recu rrence of d ysp hagia
esophagus is available for the reconstruction. (Reproduced with permission
from Orringer, MB. Complications of esophageal surgery and trauma. In:
can be established . With this aggressive initial p rogram of
Greenfield LJ , ed. Complications in surgery and trauma, 2nd ed. Philadelphia, d ilatation, long-term com fortable sw allow ing w ith little
PA: J .B. Lippincott; 1990:317.) or no need for su bsequ ent d ilatations is generally
achieved (43). Few p atients requ ire anastom otic revision.
Occasionally, end oscop ic injection of steroid s into a
refractory anastom otic scar facilitates the m anagem ent of
■ Anastomotic stricture this p roblem (44,45).
Although the m anagem ent of a cervical anastom otic leak is
generally straightforw ard and seld om associated w ith
d eath, the long-term sequ elae of a cervical leak are far from
■ Pulmonary complications
inconsequ ential. As m any as 50% of cervical esop hagogas- Respiratory insufficiency after esophageal resection and
tric anastom otic leaks resu lt in an anastom otic strictu re as reconstru ction is exceed ingly com m on and is associated
healing occu rs, and this represents an u nsatisfactory ou t- w ith a mortality rate of up to 40% (46,47). Patients w ith
com e of an operation that is intend ed to provid e com fort- esophageal squamous cell cancer, particularly those treated
able sw allow ing. The im plications are sim ilar in p atients w ith preoperative chemoradiation, may have a greater risk
w ho su rvive an intrathoracic esophageal anastom otic leak. for postoperative pulmonary morbid ity, including pleural
Ou r grou p has p reviou sly rep orted in over 2000 transhiatal effusion, pneumonia and respiratory insufficiency following
esop hagectom y patients at the University of Michigan an esophagectomy (48). A vital part of minimizing postopera-
anastomotic leak rate averaging 12%, w ith nearly half of tive pulmonary complications after esophageal resection and
these p atients d evelop ing su bsequ ent anastom otic stric- reconstruction is rigorous preoperative pulmonary physio-
tu res (38), consistent w ith reports in the literatu re for the therapy. The authors insist on total abstinence from cigarette
incid ence of both anastom otic leak from 5% to 26%, and smoking for a minimum of 2 weeks before esophagectomy.
stenosis from 10% to 31% (39–42). Withou t qu estion, the Home use of an incentive inspirometer and instruction in
prevention of an anastom otic leak is the key to a su ccessfu l d eep-breathing exercises are also begun 2 w eeks preopera-
fu nctional ou tcom e in these patients. In ou r initial exp eri- tively. This investm ent of tim e and energy in im proving the
ence w ith sid e-to-sid e stapled cervical esophagogastric p atient’s p reoperative respiratory statu s is repeated ly
anastomosis, w hich has been associated w ith an anasto- rew ard ed by a low er incid ence of postop erative pu lm onary
motic leak rate of less than 3%, w e observed a d ram atic complications after esophageal resection and reconstruc-
red u ction in the need for late p ostop erative anastom otic tion. Postoperatively, patients are extubated im m ed iately
d ilatations (35). after op eration and resu me p ulmonary physiotherapy as
In the p atient w ho has exp erienced an esop hageal early as p ossible. Ad equ ate postoperative analgesia, partic-
anastom otic leak, early p assage of a N o. 46 French or u larly epid ural anesthesia, is of great valu e in minimizing
larger d ilator w ithin 1 w eek of d rainage is carried ou t to p ostoperative pu lmonary problems.
One of the most disastrous complications after esophageal

resection is the development of a fistula between the tracheo-
bronchial tree and either the esophagus or esophageal substi-
tute, generally at the anastomotic site. Among 207 patients
with malignant esophagorespiratory fistulas treated at the
Memorial Sloan-Kettering Cancer Center in New York, Burt
at al. reported that 13 patients developed their fistulas after
resections for esophageal carcinoma (49). Once a fistula
between the airway and adjacent alimentary tract develops,
there are few options other than to prevent continued con-
tamination of the respiratory tree by identifying and dividing
the fistula and repairing the airway, generally a major under-
taking in a desperately ill patient.
■ Gastric outlet obstruction

The need for a routine gastric drainage procedure follow ing
the vagotomy that inevitably accompanies esophagectomy
has been debated. It has been show n, for example, that most
patients who undergo an esophagectomy and esophagogas-
tric anastomosis w ithout a concomitant d rainage proced ure
do not d evelop d ifficulty w ith gastric outlet obstruction
(50,51). H ow ever, in a prospective trial in w hich 200 patients
undergoing esophageal resection were randomized to
receive either a pyloroplasty or no gastric d rainage proce-
dure, gastric emptying w as found to be four times longer in
those w ho d id not have a pyloroplasty (52). Ad verse post-
prand ial symptoms w ere less in those who had a drainage
procedure, and there was no morbidity from the pyloro- FIGURE 24.14. A barium study of a patient with regurgitation and dilatation
plasty. For the occasional patient w ho d oes d evelop signifi- of the intrathoracic stomach following esophagectomy for distal-third carci-
noma. This complication was the result of two technical errors: failure to
cant gastric outlet obstruction after esophageal resection enlarge the diaphragmatic hiatus sufficiently, with resultant relative obstruc-
(Fig. 24.14), the outcom e may be d isastrous aspiration pneu- tion at the diaphragmatic hiatus (large arrow), and failure to perform a gastric
monia and impaired nutrition d ue to inability to eat. Further, drainage procedure, with resultant pyloric obstruction (small arrow). (Repro-
reoperation to perform a drainage procedure may be very duced with permission from Orringer MB. Complications of esophageal sur-
gery and trauma. In: Greenfield LJ , ed. Complications in surgery and trauma,
difficult after the stomach has been mobilized into the chest. 2nd ed. Philadelphia, PA: J .B. Lippincott; 1990:318.)
For these reasons, the authors ad vocate performance of a
gastric d rainage proced ure in every patient und ergoing
esophagectomy and esophageal reconstruction, preferring a
Ramstedt-type extramucosal pyloromyotomy, w hich avoids level of the diaphragm, but the esophageal replacement,
the intra-abd om inal suture line of a pyloroplasty. After per- w hether stomach or intestine, should also be carefully
form ing the pylorom yotomy, silver clip markers placed at sutured to the ed ge of the d iaphragmatic hiatus to prevent
the level of the pylorus aid in interpreting subsequent rad io subsequent herniation of abd ominal viscera through the hia-
logic stud ies used to evaluate gastric emptying. In more than tus and into the chest (Fig. 24.15). As our group and others
1,500 such pyloromyotomy performed during esophageal have observed , this com plication may occur acutely w ithin
bypass or replacement with stomach, our group has experi- the first several d ays of operation or years after the
enced one leak postoperatively. This leak resulted in fatal esophagectomy (53,54). Such a hernia may be an asympto-
peritonitis. Intrathoracic gastric outlet obstruction may also matic find ing on a postoperative chest roentgenogram on
result from failure to enlarge the diaphragmatic hiatus ade- w hich intestinal gas is seen above the level of the hiatus, or
quately before mobilizing the stomach into the chest. The the patient may present w ith vague left upper quad rant
diaphragmatic hiatus should accommodate at least three fin- abdominal or lower thoracic discomfort, nausea, and vomit-
gers comfortably alongsid e the mobilized stomach to pre- ing as is the case w ith chronic traumatic d iaphragmatic her-
vent this complication. nias. Because the risk of incarceration and strangulation of
the herniated viscera is substantial, red uction of the hernia is
advised . Herniation of intestine through the diaphragmatic
■ Diaphragmatic hiatus obstruction or herniation hiatus follow ing esophagectomy can generally be repaired
Not only must the hiatus be enlarged sufficiently to prevent transabd ominally. In the case of chronic traumatic d iaphrag-
the esophageal substitute from becoming obstructed at the matic hernias, the opening in the d iaphragm is relatively
■ Chylothorax
Ow ing to the p roxim ity of the thoracic d u ct and the
esop h agu s, ch ylothorax follow ing esop h agectom y is a
recogn ized com p lication . Ligation of the d ivid ed
p eriesop hageal tissu es at the tim e of esop hagectom y
m in im izes this com p lication. Com p ared w ith the rela-
tively healthy p atient w h o su stains a ch yloth orax after
aortic su rgery, how ever, this com p lication occu rring in
the d ebilitated p atient w ith esop h ageal obstru ction is not
w ell tolerated , w ith rep orted m ortality as high as 50%
(55,56). Patients w ith chronic esop h ageal obstru ction are
alread y nu tritionally d ep leted . Fu rther loss of p rotein-
rich ch yle is n ot w ell tolerated . Only a few d ays shou ld
be exp end ed tryin g to treat this com p lication non op era-
tively. With aggressive op erative in tervention and d irect
ligation of th e p oin t of th oracic d u ct inju ry, p atient sal-
vage is the ru le (57). Th oracic d u ct ligation at th e p oin t
w h ere the th oracic d u ct em erges throu gh the d iap hrag-
m atic hiatu s can be accom p lish ed either by right p ostero-
lateral thoracotom y or VATS tech niqu es.
■ Pancreatitis
Postoperative pancreatitis m ay occu r follow ing esophagec-
tom y d ue to pancreatic inju ry d uring perform ance of either
the Kocher maneu ver or gastric m obilization. The possibil-
ity shou ld be su sp ected in p atients w ho d evelop u nex-
FIGURE 24.15. Herniation of the splenic flexure of the colon (large arrow) p lained fever, resp iratory d istress, or p rolonged ileu s after
through the diaphragmatic hiatus following esophageal replacement with esop hagectom y. The d iagnosis is confirm ed by d eterm in-
stomach for a caustic stricture. No sutures had been placed between the ing seru m am ylase and lip ase levels. Stand ard treatm ent of
intrathoracic stomach (small arrow) and the edge of the diaphragmatic hiatus p ancreatitis w ith nasogastric tube d ecom pression of the
to prevent this complication. (Reproduced with permission from Orringer MB.
Complications of esophageal surgery and trauma. In: Greenfield LJ , ed. Com- gastrointestinal tract and intravenou s flu id s is u su ally su f-
plications in surgery and trauma, 2nd ed. Philadelphia, PA: J .B. Lippincott; ficient, althou gh p rogression to fatal hem orrhagic pancre-
1990:318.) atitis may occu r.
■ Splenic injury
sm all and the herniated viscera m ay becom e ad herent to
ad jacent intrathoracic stru ctu res requ iring a transthoracic Injury to the spleen may occur during esophagectomy, partic-
ap p roach for red u ction. The m ajority of herniations of ularly during mobilization of the stomach for esophageal
intestine alongsid e the intrathoracic stom ach, on the other replacement. Careful avoidance of undue traction on the
hand , occu r throu gh a relatively p atu lou s hiatu s. Red u c- short gastric vessels during gastric mobilization and early
tion of the hernia and narrow ing of the hiatu s are read ily d ivision of ad hesions between the stomach and the spleen on
achieved throu gh the abd om en. As is the case w ith other opening the abdomen minimize this complication. Routine
com p lications that follow esop hageal su rgery, this situ a- splenectomy as part of the “cancer operation” for esophageal
tion can also generally be p revented . When the esop hageal carcinoma is not advocated because splenectomy is associ-
su bstitu te has been brou ght throu gh the d iap hragm atic ated with a well-documented increased morbidity of its own.
hiatu s and the anastom osis has been com p leted , several
heavy d iap hragm atic cru ral su tu res shou ld be u sed to nar-
row the hiatu s so that it ad m its three fingers alongsid e the
■ Peripheral atheroembolism
stom ach or colon. Then a few interru p ted su tu res betw een Throm boem bolic sequelae after transhiatal esophagectom y
the ed ge of the d iap hragm atic hiatu s and the visceral have been rep orted in tw o p atients and attribu ted to inad -
esop hageal su bstitu te shou ld be u sed to lim it the m igra- vertent d islod gem ent of d ebris from the d iseased aorta in
tion of other intra-abdominal viscera through the hiatus the process of m obilizing the esophagus through the
into the chest. Finally, the divided triangular ligament of the d iap hragm atic hiatu s (58). This comp lication has not been
mobilized liver should be sutured to the ed ge of the hiatus to encou ntered by ou r grou p in a com bined exp erience w ith
provide one add itional barrier to herniation at this site. m ore than 2,000 transhiatal esop hagectom ies.
■ Complications of substernal far safer and more direct to perform it w hen one does not
esophageal replacement have to negotiate the anterior angulation of the cervical
esophagus that has been anastomosed to a retrosternal graft;
Several u niqu e com p lications of esop hageal rep lacem ent and (c) the incidence of postoperative cervical anastomotic
are related to retrosternal placem ent of the esophageal su b- leak is low er. In the original esophageal bed in the neck, the
stitute. The m ost obvious is potential obstru ction at the anastomosis is buttressed by adjacent tissues: the spine pos-
level of the retrosternal neohiatus d ue to failure to create an teriorly, the carotid sheath laterally, the trachea medially, and
ad equ ate op ening. When creating a retrosternal tu nnel, it is the strap muscles anteriorly. An esophageal anastomosis to a
ou r p ractice to d ilate this sp ace u ntil the entire hand and retrosternal colon or stomach is basically subcutaneous in the
forearm can be inserted retrosternally, ensuring su fficient neck and is relatively unsupported. Coughing or a Valsalva
room for either the stomach or the colon. Com pression and maneuver against a closed upper esophageal sphincter
obstru ction of the retrosternal esop hageal su bstitu te at the results in distention of the retrosternal esophageal substitute
su p erior op ening into the anterior m ed iastinu m is a fu nc- with increased pressure on the anastomosis and a higher
tion of the p osterior p rom inence of the clavicu lar head , anastomotic leak rate. If esophageal bypass is performed in
w hich narrow s the anterior thoracic inlet. For this reason, patients with unresectable esophageal carcinoma, the distal
w hen p erform ing a retrosternal interp osition of stom ach or esophagus should be decompressed into a Roux-en-Y limb or
colon, w hich requ ires relocation of the cervical esop hagu s jejunum rather than excluded (59,60).
anteriorly from its u su al p osition to the left and posterior to
the trachea, the m ed ial third of the clavicle, the ad jacent
manu briu m , and u su ally the m ed ial first rib as w ell shou ld ■ Esophageal diverticulectomy
be resected to ensu re an ad equ ate opening into the anterior Pu lsion d iverticu la of the esophagus, w hether orop haryn-
med iastinu m . geal (Zenker d iverticulum) or intrathoracic, result from
associated d istal esop hageal obstruction, most often neuro-
■ Complications of bypassing or excluding motor d ysfunction. Thus, if the und erlying neuromotor
abnormality resp onsible for the formation of the d iverticu-
the native esophagus lum is not ad d ressed at the time of d iverticulectomy, failure
Managem ent of the d iseased native esop hagu s is contro- to relieve the d istal obstru ction m ay resu lt in d isru ption of
versial w hen p erform ing retrosternal rep lacem ent of the the su tu re line (Fig. 24.16). Follow ing resection of a d ivertic-
esop hagu s. An esop hagu s that is severely strictu red from u lum, the esophagu s should be insu fflated w ith air through
a cau stic inju ry, for exam p le, m ay sim p ly be left in the an ind w elling nasogastric tu be positioned w ithin the
p osterior m ed iastinu m and byp assed w ith a retrosternal esophagus, and an air leak should be looked for by immers-
colon. The p otential com p lications arising from the resid - ing the pouting esophageal submucosa in saline solution
u al d iseased esop hagu s, how ever, m and ate that it be (Fig. 24.17). The most opportune time to treat such a pinhole
rem oved w henever p ossible. The sm all bu t d efinite leak is at the time of operation, and a single 5-0 m onofila-
increased risk of late d evelop m ent of carcinom a in the ment stitch may avert a great deal of postoperative morbid-
cau stic strictu red esop hagu s is a less com p elling reason to ity. Alternatively, if a cervical esophageal leak occurs after
resect it than the p otential for su bsequ ent reflu x esop hagi- d iverticulectomy and esophagomyotomy, the neck w ound
tis. A cau stic inju ry m ay d estroy the low er esop hageal must be opened, irrigated, and drained, as described earlier
sp hincter m echanism ow ing to su bsequ ent fibrosis, and for the treatment of cervical anastomotic disruption. Nutri-
su ch a p atient u nd ergoing su bsternal colon interp osition tion may be maintained w ith either nasogastric feedings or
m ay d evelop reflu x sym p tom s and severe esop hagitis in total parenteral support. Broad -spectrum antibiotics are
the native esop hagu s. ad ministered . With an ad equate esophagomyotomy that has
Although substernal bypass of the excluded esophagus relieved the distal obstruction, the incidence of leak from a
with either stomach or colon has been used for treatment of d iverticulectomy suture line should be exceedingly low (61).
both benign and malignant disease, the complications from If a cervical salivary fistula does occur, however, sponta-
such an approach are appreciable. The excluded esophagus neous closure w ithin 7 to 10 d ays should be expected . If an
may become a giant posterior mediastinal mucocele that intrathoracic esophageal suture line leak occurs w ithin sev-
causes respiratory d istress due to tracheobronchial compres- eral d ays of d iverticulectomy, imm ed iate re-exploration of
sion. Of more immediate concern in the postoperative period the chest w ith closure of the fistula and reinforcement w ith
is the incidence of disruption of the distal end of the exclud ed anterior med iastinal fat, ad jacent pleura, intercostal muscle,
esophagus w ith resultant left subphrenic abscess. When or omentum is indicated.
esophageal replacement is necessary for benign d isease, the
authors advocate resection of the esophagus. It is always ■ Esophagomyotomy for achalasia or
preferable to place the esophageal substitute in the posterior
mediastinum in the original esophageal bed because (a) this
esophageal spasm
is the shortest distance between the neck and the abdominal The m egaesop hagu s of achalasia m ay contain 1 to 2 liters of
cavity; (b) if subsequent anastomotic dilation is required, it is stagnant intraesop hageal contents. Ind u ction of general
FIGURE 24.16. A: This esophagogram shows an

esophagopleural cutaneous fistula (large arrow) and a
recurrent esophageal diverticulum (small arrow) in a patient
who had undergone prior resection of the diverticulum with-
out an esophagomyotomy. B: The patient’s underlying
esophageal neuromotor problem is evident in this view from
the same study, showing a typical corkscrew esophagus.
The relative obstruction secondary to intermittent spasm
distal to the esophageal suture line had not been relieved
when the diverticulum was resected; hence disruption of
the suture line with fistula formation and recurrence of the
diverticulum (arrow) followed. (Reproduced with permission
from Orringer MB. Complications of esophageal surgery and
trauma. In: Greenfield LJ, ed. Complications in surgery and
trauma, 2nd ed. Philadelphia, PA: J.B. Lippincott; 1990:320.)
A B
anesthesia in su ch a patient represents the m ost d angerou s rigid esop hagoscop y is carried ou t, and the esop hagu s is
part of the op eration. Becau se a nasogastric tube interferes evacu ated and irrigated .
w ith d eep breathing and ad equ ate clearing of p u lm onary After com p letion of the esophagom yotom y for either
secretions, one shou ld not u se an intraesophageal nasogas- achalasia or esophageal spasm, integrity of the esophageal
tric tu be p reop eratively to d ecom p ress the d ilated esop ha- mucosa is d ocumented by insufflating air into the esopha-
gu s. Rather, the p atient is restricted to a clear liqu id d iet for gus through an ind w elling intraesophageal nasogastric
2 d ays before the operation, and then im m ed iately before tube. As d escribed earlier, id entification and closure of an
ind u ction of general anesthesia, w ith the patient in a sitting inad vertent esop hageal inju ry at this point is far sim p ler
position, a nasogastric tu be is passed , and the esop hagu s is than w hen the p erforation is d etected hou rs to d ays after
asp irated and evacu ated . Rapid -sequence ind u ction of op eration. Patients w ith achalasia are frequ ently referred
anesthesia is then carried ou t w hile constant p ressu re is for op eration follow ing failed p neu m atic d ilatation or,
maintained on the cricoid cartilage to prevent regurgitation m ore recently, u nsu ccessfu l intrasp hincteric injection of
of esop hageal contents into the p harynx u ntil the end otra- botulinum toxin. These previous endoscopic interventions
cheal tu be balloon is inflated . Once the airw ay is p rotected , may increase the difficulty in identifying tissue planes prior
to successful esophagomyotomy. In particular, patients who
have previously undergone botulinum toxin injection, and
Air obtained some relief of achalasia symptoms, are more likely
bubbles to have periesophageal fibrosis resulting in a greater risk, as
Distended high as 50%, for esophageal perforation during esophagomy-
mucosa
otomy and less palliation of their symptoms following opera-
tion. Periesophageal fibrosis w as less prevalent among
patients who had previously been treated by pneumatic
dilatation and did not appear to affect surgical outcomes fol-
FIGURE 24.17. Testing for inadvertent esophageal perforation following lowing esophagomyotomy (62,63).
esophagomyotomy. The esophageal mucosa is distended by insufflating air Regard less of the ap p roach u sed , p oten tial com p lica-
down an intraesophageal nasogastric tube. Air bubbles escaping from the tions exist and m ay requ ire reop eration in 10% to 15% of
esophagus submerged under saline indicate a perforation. (Reproduced with
p atients follow ing esop hagom yotom y. If a com p lete d is-
permission from Orringer MB. Complications of esophageal surgery and
trauma. In: Greenfield LJ , ed. Complications in surgery and trauma, 2nd ed. tal esop hagom yotom y is not p erform ed and the obstru c-
Philadelphia, PA: J .B. Lippincott; 1990:322.) tion relieved , d ysp hagia and regu rgitation w ill continu e
in the im m ed iate p ostop erative p eriod and reop eration (76), and these factors should be taken into consideration in
m ay be n ecessary (64). Alternatively, if the esop h agom y- determining whether patients should und ergo esophagomy-
otom y is carried on to th e stom ach to ensu re ad equ ate otomy or primary esophagectomy.
relief of the esop hageal obstru ction, the u ncoord inated
low er esop hageal sp hincter m ay be converted to an
incom p etent one, w ith ensu ing long-term com p lications ■ REFERENCES
of reflu x esop h agitis. Fu rtherm ore, “long” esop h agom y- 1. H end erson RD, Boszko A, Van N ostrand AW, et al. Pharyngoe-
otom y, over 5 cm w ith extension on to th e stom ach, has sophageal d ysp hagia and recu rrent laryngeal nerve p alsy. J Thorac
been associated w ith “d iverticu larization” of the m u cosa Cardiovasc Surg 1974;68:507–512.
2. Salam a FD, Lam ont G. Long-term resu lts of the Belsey Mark IV antire-
in long-term follow -u p (65,66). flu x op eration in relation to the severity of esop hagitis. J Thorac Cardio-
Controversy exists about the need for a concomitant vasc Surg 1990;100:517–519.
antireflux procedure w ith the d istal esophagomyotomy, 3. Orringer MB, Skinner DB, Belsey RH . Long-term resu lts of the Mark IV
operation for hiatal hernia and analyses of recurrences and their treat-
w hich may rend er the low er esophageal sphincter incompe- m ent. J Thorac Cardiovasc Surg 1972;63:25–33.
tent (67–69). With a few notable exceptions, the majority of 4. Pearson FG, Langer B, H end erson RD. Gastrop lasty and Belsey h ia-
esophageal surgeons now advocate partial fundoplication to tu s hernia rep air. An op eration for the m anagem ent of p ep tic stric-
tu re w ith acqu ired short esop hagu s. J Thorac Cardiovasc Surg 1971;61:
prevent the subsequent development of gastroesophageal 50–63.
reflux follow ing esophagomyotomy for achalasia (70). A 5. Orringer MB, Orringer JS, Dabich L, et al. Com bined Collis gastro-
Belsey-type partial fundoplication has been recommend ed p lasty–fu nd op lication operations for sclerod erm a reflu x esop hagitis.
Surgery 1981;90:624–630.
w hen esophagomyotomy is approached transthoracically, 6. Pearson FG. H iatu s hernia and gastroesop hageal reflu x: ind ications for
w hereas Toupet (posterior) or Dor (anterior) fund oplication surgery and selection of op eration. Sem Thorac Cardiovasc Surg 1997;9:
is typically recommended follow ing transabdominal 163–168.
7. Lam TC, Fok M, Cheng SW, et al. Anastom otic com p lications after
esophagomyotomy. When performing a fundoplication to esophagectom y for cancer. A com p arison of neck and chest anasto-
ensure low er esophageal sphincter competence in an atonic m oses. J Thorac Cardiovasc Surg 1992;104:395–400.
esophagus, care must be exercised to avoid subsequent 8. Michel L, Grillo H C, Malt RA. Esop hageal p erforation. Ann Thorac Surg
1982;33:203–210.
obstruction d ue to an overaggressive fund oplication. 9. White RK, Morris DM. Diagnosis and m anagem ent of esop hageal p er-
Am ong the m ore d ifficu lt p roblem s of su rgery for acha- forations. Am Surg 1992;58:112–119.
lasia is the d evelop m ent of recu rrent d ysp hagia and regu r- 10. Bu fkin BL, Miller JI Jr, Mansou r KA. Esop hageal p erforation: em p hasis
on m anagem ent. Ann Thorac Surg 1996;61:1447–1451.
gitation d u e to esop hageal obstru ction occu rring 1 or m ore 11. Bahnson TD. Strategies to m inim ize the risk of esop hageal inju ry d u r-
years after a p reviou s esop hagom yotom y. Althou gh ing catheter ablation for atrial fibrillation. Pacing Clin Electrophysiol.
esop hagom yotom y has becom e the stand ard su rgical 2009;32:248–260.
12. Zw ischenberger JB, Savage C, Bid ani A. Su rgical asp ects of esop hageal
ap p roach to p atients w ith achalasia, in those w ith a tortu - d isease: perforation and cau stic injury. Am J Resp Crit Care Med 2002;165:
ou s m egaesop hagu s and a su p rad iap hragm atic p ou ch of 1037–1040.
esop hagu s, d elayed esop hageal em p tying m ay occu r even 13. Cam eron JL, Kieffer RF, H end rix TR, et al. Selective nonop erative m an-
agem ent of contained intrathoracic esop hageal d isru p tions. Ann Thorac
after a satisfactory esop hagom yotom y. Fu rtherm ore, the Surg. 1979;27:404–408.
p atient w ho has u nd ergone a p reviou s esop hagom yotom y 14. And ersen OS, Giu stra PE. N onop erative m anagem ent of contained
and has recu rrent sym p tom s has only a 40% to 70% chance esophageal perforation. Arch Surg 1981;116:1214–1217.
15. Michel L, Grillo H C, Malt RA. Op erative and nonop erative m anage-
of exp eriencing a good resu lt from a “red o” esop hagom y- m ent of esop hageal p erforations. Ann Surg 1981;194:57–63.
otom y (71,72). Finally, esop hagom yotom y rem ains a p al- 16. Flynn AE, Verrier ED, Way LW, et al. Esop hageal p erforation. Arch Surg
liative op eration for p atients w ith esop hageal m otor 1989;124:1211–1214.
17. Whyte RI, Iannettoni MD, Orringer MB. Intrathoracic esop hageal p er-
d isord ers involving the bod y of the esop hagu s and low er foration: the m erit of p rim ary rep air. J Thorac Cardiovasc Surg 1995;109:
esop hageal sp hincter. Patients w ith achalasia rem ain at 140–146.
risk for the d evelop m ent of esop hageal squ am ou s cell car- 18. Orringer MB. Com plications of esop hageal su rgery and trau m a. In:
Greenfield LJ, ed . Complications in surgery and trauma Philad elp hia, PA:
cinom a, and shou ld u nd ergo rou tine su rveillance u p p er J.B. Lip p incott; 1990:313.
end oscop y follow ing esop hagom yotom y. In p atients w ith 19. Gou ge TH , Dep an H J, Sp encer FC. Exp erience w ith the Grillo p leu ral
either recu rrent or p ersistent sym p tom s of achalasia w ith w rap p roced ure in 18 p atients w ith p erforation of the thoracic esop ha-
gu s. Ann Surg 1989;209:612–617.
or w ithou t associated reflu x esop hagitis, esop hagectom y 20. Wright CD, Mathisen DJ, Wain JC, et al. Reinforced p rim ary rep air of
m ay p rovid e the best op tion, elim inating the esop hageal thoracic esop hageal perforation. Ann Thorac Surg 1995;60:245–248.
obstru ction as w ell as the p otential for late d evelop m ent of 21. Iannettoni MD, Vlessis AA, Whyte RI, et al. Fu nctional ou tcom e after
su rgical treatm ent of esop hageal p erforation. Ann Thorac Surg 1997;64:
carcinom a (73). Several grou p s have su ggested that the 1606–1609.
p resence of m egaesop hagu s d oes not p reclu d e su ccessfu l 22. H ernand ez L, Jacobson J, H arris M. Com p arison am ong the p erfora-
esop hagom yotom y (74,75), p articu larly if the long axis of tion rates of Maloney, balloon, and savary d ilation of esop hageal stric-
tu res. Gastrointest Endosc 2000;51:460–462.
the esop hagu s rem ains near-vertical (75). In contrast, oth- 23. Ku bba H , Spinou E, Brow n D. Is sam e-d ay d ischarge su itable follow ing
ers have show n that d u ration of sym p tom s, sigm oid al rigid esop hagoscop y? Find ings in a series of 655 cases. Ear Nose Throat
esop hagu s (m egaesop hagu s), and d im inished low er J 2003;82:33–36.
24. Puchakayala MR, Abbey K, H aft J, et al. Delayed p ericard ial tam p on-
esop hageal sp hincter p ressu res ap p ear to be factors p read e follow ing transthoracic hiatal hernia rep air. J Cardiothorac Vasc
d ictive of w orse ou tcom es follow ing esop hagom yotom y Anesth 2006;20:245–246.
25. Patel H J, Tan BB, Yee J, et al. A tw enty-five year exp erience w ith open 51. Lu d w ig DJ, Thirlby RC, Low DE. A p rosp ective evalu ation of d ietary
p rim ary transthoracic rep air of p araesop hageal hiatal hernia. J Thorac statu s and sym p tom s after near-total esop hagectom y w ithou t gastric
Cardiovasc Surg 2004;127:843–849. em p tying p roced u re. Am J Surg 2001;181:454–458.
26. Khaitan L, Ray WA, H olzm an MD, et al. H ealth care u tilization after 52. Fok M, Cheng SW, Wong J. Pylorop lasty versu s no d rainage in gastric
m ed ical and su rgical therapy for gastroesophageal reflux d isease: a rep lacem ent of the esophagu s. Am J Surg 1991;162:447–452.
p op u lation-based stu d y, 1996 to 2000. Arch Surg 2003;138:1356–1361. 53. Katariya K, H arvey JC, Pina E, et al. Com p lications of transhiatal
27. Bow ers SP, Mattar SG, Sm ith CD, et al. Clinical and histologic follow - esop hagectom y. J Surg Oncol 1994;57:157–163.
u p after antireflu x su rgery for Barrett’s esop hagu s. J Gastrointest Surg 54. Heitmiller RF, Gillinov AM, Jones B. Transhiatal herniation of colon after
2002;6:532–539. esophagectomy and gastric pull-up. Ann Thorac Surg 1997;63:554–556.
28. Watson DI, Baigrie RJ, Jam ieson GG. A learning cu rve for laparoscopic 55. Merigliano S, Molena D, Ru ol A, et al. Chylothorax com p licating
fu nd op lication. Definable, avoid able, or a w aste of tim e? Ann Surg esophagectomy for cancer: A plea for early thoracic duct ligation. J Thorac
1996;224:198–203. Cardiovasc Surg 2000;119:453–457.
29. N ason KS, Lu ketich JD, Qu reshi I, et al. Lap aroscop ic rep air of giant 56. Wem yss-H old en SA, Lau nois B, Mad d ern GJ. Managem ent of thoracic
paraesop hageal hernia resu lts in long-term p atient satisfaction and a d u ct injuries after oesophagectom y. Br J Surg 2001;88:1442–1448.
d u rable repair. J Gastrointest Surg 2008;12:2066–2075. 57. Orringer MB, Blu ett M, Deeb GM. Aggressive treatm ent of chylothorax
30. Pearson FG, Cooper JD, Ilves R, et al. Massive hiatal hernia w ith incar- com p licating transhiatal esop hagectom y w ithou t thoracotom y. Surgery
ceration: a report of 53 cases. Ann Thorac Surg 1983;35:45–51. 1988;104:720–726.
31. Maziak DE, Tod d TR, Pearson FG. Massive hiatu s hernia: evalu ation 58. Magee MJ, Land reneau RJ, Keenan RJ, et al. Perip heral athero-
and surgical m anagem ent. J Thorac Cardiovasc Surg 1998;115:53–60. em bolism from the aorta com p licating transhiatal esop hagectom y. Am
32. Johnson AB, Od d sd ottir M, H u nter JG. Lap aroscop ic Collis gastro- Surg 1994;60:634–637.
plasty and N issen fu nd op lication. A new techniqu e for the m anage- 59. Kirschner M. Ein neu es verfahren d er oesop hagu s p lastik. Arch Klin
m ent of esophageal foreshortening. Surg Endosc 1998;12:1055–1060. Chir 1920;114:606–663.
33. Tatu m R, Shalhu b S, Oelschlager B, et al. Com p lications of PTFE m esh 60. Meu nier B, Stasik C, Raou l J-L, et al. Gastric byp ass for m alignant
at the d iap hragm atic hiatu s. J Gastrointest Surg 2008;12:953–957. esop hagotracheal fistu la: a series of 21 cases. Eur J Cardiothorac Surg
34. Stad lhuber R, Sherif A, Mittal S, et al. Mesh com p lications after p ros- 1998;13:184–189.
thetic reinforcem ent of hiatal closu re: a 28-case series. Surg Endosc 2009; 61. Varghese TK Jr, Marshall B, Chang AC, et al. Su rgical treatm ent of
23:1219–1226. ep ip hrenic d iverticu la: a 30-year exp erience. Ann Thorac Surg 2007;84:
35. Orringer MB, Marshall B, Iannettoni MD. Elim inating the cervical 1801–1809.
esophagogastric anastom otic leak w ith a sid e-to-sid e stapled anasto- 62. Patti MG, Feo CV, Arcerito M, et al. Effects of p reviou s treatm ent on
m osis. J Thorac Cardiovasc Surg 2000;119:277–288. results of laparoscop ic H eller m yotom y for achalasia. Dig Dis Sci
36. Orringer M, Lem m er J. Early d ilation in the treatm ent of esop hageal 1999;44:2270–2276.
d isru ption. Ann Thorac Surg 1986;42:536–539. 63. Wiechm ann RJ, Ferguson MK, N au nheim KS, et al. Vid eo-assisted su r-
37. Iannettoni MD, Whyte RI, Orringer MB. Catastrop hic com p lications of gical m anagem ent of achalasia of the esop hagu s. J Thorac Cardiovasc
the cervical esophagogastric anastom osis. J Thorac Cardiovasc Surg Surg 1999;118:916–923.
1995;110:1493–1500. 64. Patti MG, Molena D, Fisichella PM, et al. Lap aroscop ic H eller
38. Orringer MB, Marshall B, Chang AC, et al. Tw o thou sand transhiatal m yotom y and Dor fund oplication for achalasia: analysis of successes
esop hagectom ies: changing trend s, lessons learned . Ann Surg 2007;246: and failu res. Arch Surg 2001;136:870–877.
363–372. 65. Chen LQ, Chughtai T, Sid eris L, et al. Long-term effects of m yotom y
39. Dew ar L, Gelfand G, Finley RJ, et al. Factors affecting cervical anasto- and p artial fund oplication for esop hageal achalasia. Dis Esoph 2002;15:
m otic leak and stricture form ation follow ing esophagogastrectom y 171–179.
and gastric tube interp osition. Am J Surg 1992;163:484–489. 66. Ellis FH Jr. Failu re after esop hagom yotom y for esop hageal m otor d is-
40. Vignesw aran WT, Trastek VF, Pairolero PC, et al. Transhiatal ord ers. Causes, prevention, and m anagem ent. Chest Surg Clin N Am
esophagectomy for carcinoma of the esophagus. Ann Thorac Surg 1993;56: 1997;7:477–487.
838–844. 67. Richard s WO, Sharp KW, H olzm an MD. An antireflu x p roced u re
41. Gand hi SK, N au nheim KS. Com p lications of transhiatal esophagec- shou ld not rou tinely be ad d ed to a H eller m yotom y. J Gastrointest Surg
tom y. Chest Surg Clin N Am 1997;7:601–610. 2001;5:13–16.
42. Rice TW. Anastom otic strictu re com p licating esop hagectom y. Thorac 68. Peters JH . An antireflu x p roced u re is critical to the long-term ou tcom e
Surg Clin 2006;16:63–73. of esophageal m yotom y for achalasia. J Gastrointest Surg 2001;5:17–20.
43. Ch an g AC, Orrin ger MB. Man agem en t of th e cervical esop h agogas- 69. Lyass S, Thom an D, Steiner JP, et al. Cu rrent statu s of an antireflu x p ro-
tric an astom otic strictu re. Sem Thorac Cardiovasc Surg 2007;19: ced ure in laparoscop ic H eller m yotom y: ou tcom es of laparoscopic fu n-
66–71. d op lication for gastroesop hageal reflu x d isease and p araesop hageal
44. Kirsch M, Blu e M, Desai RK, et al. Intralesional steroid injections for hernia. Surg Endosc 2003;17:554–558.
pep tic esop hageal strictu res. Gastrointest Endosc 1991;37:180–182. 70. Ellis FH Jr, Watkins E Jr, Gibb SP, et al. Ten to 20-year clinical resu lts
45. Lee M, Ku bik C, Polham u s C, et al. Prelim inary exp erience w ith end o- after short esop hagom yotom y w ithout an antireflux proced ure (m od i-
scop ic intralesional steroid injection therap y for refractory u p p er gas- fied H eller operation) for esop hageal achalasia. Eur J Cardiothorac Surg
trointestinal strictu res. Gastrointest Endosc 1995;41:598–601. 1992;6:86–89.
46. Law SY, Fok M, Cheng SW, et al. A com p arison of ou tcom e after resec- 71. Gorecki PJ, H ind er RA, Libbey JS, et al. Red o lap aroscop ic su rgery for
tion for squ am ou s cell carcinom as and ad enocarcinom as of the esop h- achalasia. Surg Endosc 2002;16:772–776.
agus and card ia. Surg Gyn Obstet 1992;175:107–112. 72. Ellis FH Jr, Crozier RE, Gibb SP. Reop erative achalasia su rgery. J Thorac
47. Gillinov AM, H eitm iller RF. Strategies to red u ce p u lm onary com p lica- Cardiovasc Surg 1986;92:859–865.
tions after transhiatal esop hagectom y. Dis Esoph 1998;11:43–47. 73. Devaney EJ, Lannettoni MD, Orringer MB, et al. Esop hagectom y for
48. Doty JR, Salazar JD, Forastiere AA, et al. Postesop hagectom y m orbid - achalasia: p atient selection and clinical exp erience. Ann Thorac Surg
ity, m ortality, and length of hosp ital stay after p reop erative chem orad i- 2001;72:854–858.
ation therap y. Ann Thorac Surg 2002;74:227–231. 74. Patti MG, Pellegrini CA, H organ S, et al. Minim ally invasive su rgery
49. Burt M, Diehl W, Martini N , et al. Malignant esop hagoresp iratory fis- for achalasia: an 8-year exp erience w ith 168 p atients. Ann Surg 1999;
tu la: m anagem ent op tions and su rvival. Ann Thorac Surg 1991;52: 230:587–593.
1222–1228. 75. Eldaif SM, Mutrie CJ, Rutledge WC, et al. The risk of esophageal resection
50. Urschel JD, Blew ett CJ, You n g JE, et al. Pyloric d rainage (p yloro- after esophagomyotomy for achalasia. Ann Thorac Surg 2009;87:1558–1563.
p lasty) or no d rainage in gastric recon stru ction after esop hagectom y: 76. Schu chert MJ, Luketich JD, Land reneau RJ, et al. Minim ally-invasive
a m eta-an alysis of rand om ized con trolled trials. Dig Surg 2002;19: esop hagom yotom y in 200 consecu tive p atients: factors influ encing
160–164. p ostoperative ou tcom es. Ann Thorac Surg 2008;85:1729–1734.
CHAPTER
25
Complications of Pulmonary
and Chest Wall Surgery
Christina H. Wei and J essica S. Donington
■ INTRODUCTION and its morbid ity and mortality data represent a modern
benchmark for patients undergoing major pulmonary resec-
Thoracic su rgery ou tcom es are d epend ent on m any factors tion in the United States and Canad a. Overall mortality in the
inclu d ing p atient’s card iop u lm on ary health, sm okin g series w as 1.4%, with no increase in mortality w ith more
statu s, p rim ary thoracic p athology, extent of resection, extensive resections, although the trial was not designed to
anesthetics, and qu ality of p re- and p ostop erative care. detect that difference (Table 25.1). One or more complications
When com p lications arise, early and p rom p t recognition occurred in 38% of patients, with atrial arrhythmias seen in
is im p ortant. Th e m ajority of p u lm onary an d chest w all 14%, prolonged chest tube d uration in 11%, and persistent air
resections are related to th e treatm en t of non -sm all cell leaks in 8% being most common (Table 25.2). Other contem-
lung cancer (N SCLC). This is a tobacco associated m alig- porary series from Strand et al. (3) and Licker et al. (4) report
nancy and therefore a significant p rop ortion of p atients similar mortality to the ACOSOG trial at 4.4% and 2.9%
u nd ergoing resection have other tobacco related com or- respectively. A series from Dominguez-Ventura et al. (5) look-
bid ities inclu d ing coronary artery d isease, hypertension, ing exclusively at surgical outcome in octogenarians reported
p erip heral vascu lar d isease, chronic obstructive lung d is- mortality of 6.3% and overall morbidity of 48%. A history of
ease (COPD). It is also a d isease of the eld erly w ith the chronic heart failure or myocardial infarction (MI) was an
m ed ian age of d iagnosis at 67 (1). These factors contribu te ind icator of increased mortality, and the greatest increase in
to a relatively frail su rgical pop ulation. morbidity compared to a younger population w as in the rate
of atrial arrhythmias (21%).
■ SURGERY FOR LUNG CANCER
Surgery remains the primary form of treatment for patients ■ INTRAOPERATIVE COMPLICATIONS
w ith early stage NSCLC (1). This includes tumors limited to ■ Intraoperative hemorrhage
the lung and intrapulmonary lymph nodes, but also encom-
passes tumors that extend into the chest w all and select Massive intraop erative hem orrhage is u su ally the resu lt
tumors that involve mediastinal lymph nodes. Lobectomy of inju ry to a p u lm onary artery or vein branch su stained
via video assisted thoracoscopic surgery (VATS) or standard d u ring d issection. The p u lm onary arteries are thin w alled
posterior lateral thoracotomy, with mediastinal lymph node and p rone to inju ry d u ring traction or m anip u lation. The
dissection is the current standard of care for medically fit w all of p u lm onary veins is m ore resilient and can better
patients with early stage NSCLC. Over the past decade, there w ithstand su rgical m anip u lation. Inflam m atory changes
has been a meaningful reduction in the morbidity and mor- to the su rrou nd ing soft tissue resulting from neoad ju vant
tality associated with pulmonary resections. This is attrib- chem otherap y, rad iation therap y, or chronic infection can
uted to improved patient selection, advances in anesthesia rend er d issection m ore d ifficu lt. Exp ed itiou s control of
care and surgical technology, and improved postoperative bleed ing is cru cial and can usually be accom plished w ith
care. The American College of Surgeons Oncology Group ap p lication of p ressu re to the bleed ing site. The su rgeon
(ACOSOG) recently published operative morbid ity and mor- should be cognizant of the patient’s hem od ynamic statu s
tality results of Z0030, a phase III trial, which compared sys- d u ring this tim e. Mod e of rep air is d ep end ent on the size
tematic mediastinal lymph node sampling to complete and location of inju ry. The fragile natu re of the p ulmonary
mediastinal lymph nod e dissection in clinical stage I and II artery often m and ates p roxim al hilar control to assu re ten-
NSCLC patients undergoing surgical resection (2). The trial sion free repair.
randomized 1,023 patients from 102 different institutions,
■ Ventilatory complications
Christina H. Wei, Jessica S. Donington: N YU School of Intraoperative ventilatory complication can be a result of
Med icine, Dep artm ent of Card iothoracic Su rgery, N ew York, multiple causes. Ventilation circuitry should be assessed and
N Y 10016. appropriate placement and position of the end otracheal tube
276
Chapter 25 • Complications of Pulmonary and Chest Wall Surgery 277
Table 2 5 .1 O p er a t ive m or t a lit y follow in g lu n g ca n cer r esect ion s

Mortality
Study Year N Overall (%) Pneumonectomy (%) Bilobectomy (%) Lobectomy (%) Sublobar (%)
Strand 2007 4,395 4.4 8.6 7.3 2.5 2.2
Allen 2006 1,023 1.37 0 5 1 3
Dominguez-Ventura 2006 379 6.3 8 14.3 5 8.4
Rostad 2006 3,224 8.0 11.6 N/R 5.3 N/R
Licker 1999 634 3.2 7.9 3 1.2 2.7
Romano 1992 12,439 5.0 11.6 N/R 3.9 3.7
Wada 1988 7,099 1.3 3.2 N/R 1.2 0.8
Ginsberg 1983 2,220 3.7 6.2 N/R 2.9 1.4
Weiss 1974 547 12.4 17 N/R 10 0
confirm ed . Double lumen end otracheal tubes (DLETT) are ventilation. This typically results in an acute increase in the
frequently used d uring pulm onary resections and greatly airway pressure, hypotension, loss of rhythmic movement
facilitate surgery by provid ing lung collapse and a quiet sur- of med iastinum, or bulging med iastinum. This problem can
gical field but require more precise positioning than stan- be alleviated by opening into the contralateral pleural space
dard single lumen tubes. If the DLETT is advanced too far, it through the med iastinum.
occlud es the take off of left upper lobe orifice, resulting in
hypoxia and hypoventilation during right-sided resections.
Withd raw al of the tube can relieve the obstruction. The
■ POSTOPERATIVE COMPLICATIONS
DLETT can also be placed too proximally, resulting in poor ■ Postoperative bleeding
lung isolation or occlusion of the right main stem bronchus
Etiology and Risk Factors
by the herniated bronchial cuff. This can be prevented by
bronchoscopic confirmation of tube position after the patient Substantial postop erative bleed ing follow ing p ulmonary
is placed in the decubitus position. Patients w ith pre-existing resections is rare. Inad equ ate intraop erative hem ostasis
emphysema are at risk of ventilator-associated pneumotho- is the most com m on reason for p ostop erative bleed ing (6).
rax. Pneumothorax can occur in the contralateral lung d ur- Accord ing to a N ational Veterans Affairs Surgical Qu ality
ing surgery while the patient is on positive pressure Im p rovem ent Program , w hich analyzed ou tcom es after
Table 2 5 .2 O p er a t ive m or bid it y follow in g lu n g ca n cer r esect ion s

Study
Licker (1999) Dominguez-Ventura Allen (2006)
Complication n 634 (2006) n 379 n 1,023
One or more complication N/R 48 38
Air leaks 7 days (%) N/R 7 7.6
Chest tube 7 days (%) N/R N/R 11.5
Chylothorax (%) N/R 1.0 1.3
Hemorrhage (%) 0.6 1.0 2.4
Myocardial infarction (%) 2.4 4.0 0.9
Empyema N/R 1.0 1.1
Recurrent nerve injury (%) N/R 2.0 0.7
Arrhythmia (%) N/R 21.0 14.4
Respiratory failure (%) 1.3 6.0 5.5
Broncho-pleural fistula (%) N/R N/R 0.5
Pneumonia (%) 0.8 4.0 2.5
3,516 lu ng resections, significant postoperative bleed ing, Prophylaxis inclu d es the u se of mechanical means w ith
d efined as requiring 4 units transfusion, occu rred in 3% compression hose and intermittent compression d evices
of patients (7). Factors associated w ith postoperative bleed - and pharmacological means w ith low d ose hep arin. The
ing inclu d e a history of antiplatelet or anticoagu lation ther- prophylaxis shou ld be started prior to the ind uction of anes-
apy and neoad ju vant rad iation or chem otherapy (8). thesia and continued throughout the hospital course.
Clinical Presentation
■ Cardiac arrhythmia
Presentation can range from obvious to occult. The common
threshold s for reoperation for postoperative bleed ing Etiology and Risk Factors
includ e a chest tube output of 1,000 mL in 1 hour or 200 mL/ Card iac arrhythm ia, sp ecifically atrial fibrillation (AF), is
hour for 2 to 4 hou rs. H ow ever, low chest tu be outpu t d oes by far the m ost com m on card iac com plication after thoracic
not exclu d e active bleed ing since the chest tu be can clot. In su rgery, w ith an incid ence of 4% after w ed ge resection, 10%
occult cases, p atients rem ain hem od ynamically stable bu t to 20% follow ing lobectomy, and 40% after p neu m onec-
bleed slow ly into the thorax w ith retained blood that tom y (12,13). The incid ence of AF after lobectom y d oes not
evolves into clotted hemothorax. d iffer for op en and VATS ap p roaches (14). The p eak onset
of AF is 2 to 3 d ays p ost su rgery. Patients w ho d evelop peri-
Management and Prevention op erative AF are at increased risk for stroke. The risk of
H em od ynamic stabilization and reversal of coagulopathy stroke related to p ostop erative AF is 1.9% (15). The only
are the initial m anagem ent steps, follow ed by a d ecision for consistent ind ep end ent p reop erative risk factor for d evel-
re-exp loration. The goals at re-exploration are controlling op m ent of atrial arrhythm ia is age greater than 60 (12).
ongoing blood loss and evacu ation of retained hem otho- Other p red ictors inclu d e m ale gend er, history of AF, and
rax. Sou rces of bleed ing inclu d e med iastinal, bronchial, p rolonged P w ave on a 12-lead electrocard iogram (ECG).
intercostal, and hilar vessels, or along lu ng parenchym al Another interesting pred ictor is a tw ofold increase in w hite
staple lines in the lu ng. In m any cases, no specific site of cou nt on the first p ostop erative d ay, w hich is m ost likely a
bleed ing is id entified at re-exploration. reflection of increased ad renergic activation post su rgery
(16). Other arrhythm ias are m u ch less frequ ently encou n-
■ Thromboembolism tered . The incid ence of su stained ventricu lar tachycard ia is
1.6% and the incid ence of brad yarrhythmias requiring
Etiology and Risk Factors treatm ent is 0.4% (12).
Venous throm boem bolism is a relatively rare but poten-
tially d evastating comp lication of pu lm onary su rgery. Tho- Treatment and Prevention
racic su rgical p roced u res are consid ered a m od erate risk There are four key treatment issues with regard to postopera-
for the d evelopm ent of d eep venou s throm bosis (DVT) d ue tive AF: (a) control of ventricular response, (b) conversion to
to the increased p eriop erative hypercoagu lable state. The normal sinus rhythm, (c) prevention of thromboembolic
classic Virchow ’s triad of stasis (from anesthetics), hyp erco- events, and (d ) prophylaxis (17). In patients w ith postopera-
agulability (associated w ith tobacco use, m alignancy, and tive AF without structural heart d isease, w ho are hemody-
age), and end othelial inju ry (from su rgery) are p resent in namically stable, rate-controlling agents such as -blockers
most thoracic su rgery p atients. The incid ence of throm - or calcium channel blockers are recommend ed. Rhythm con-
boem bolism in p atients u nd ergoing p ulm onary resection is trol agents such as amiodarone show no overt advantage
betw een 7% and 14% for DVT and up to 5% for pulm onary over rate control agents (18). For hemodynamically unstable
em bolism (PE) (9–11). patients, card ioversion is recommend ed to quickly achieve
stability. Once arrhythmia resolves, the rate or rhythm con-
Clinical Presentation trol agent is continued for 8-w eek treatment. With appropri-
PE presents w ith su d d en respiratory d istress, hypotension, ate pharmacologic intervention, approximately 85% of these
tachycard ia, syncop e, or circulatory arrest (9). Am bu lation cases will resolve before hospital discharge. In cases of per-
in the early postop erative period shou ld be monitored sistent AF, about 98% w ill revert back to sinus rhythm w ithin
since m any sym p tom atic cases of PE occu r d u ring p atients’ tw o months of surgery (18). Contraind ications of commonly
first w alking attem p t. prescribed antiarrhythmic agents exist and vary accord ing
to individual medical history. Card iology consultation is rec-
Diagnosis and Prevention ommended in complex cases.
Diagnosis of PE is most commonly mad e by contrast com- Anoth er im p ortant asp ect of AF treatm ent is p reven-
puted tomography (CT) of the chest performed w ith spe- tion of throm boem bolism . The p oten tial for th e d evelop -
cific PE protocols. Once d iagnosed , patients are typically m ent of throm boem bolic even ts u su ally occu r w ithin 24
placed on anticoagu lation therapy. Thrombolytic therapy is to 48 hou rs of new -onset AF; hen ce, p rom p t restoration of
not an op tion in the early postoperative period . Throm - sinu s rhythm is cru cial and anticoagu lation shou ld be
boembolectomy is an op tion for only a very select grou p of consid ered for arrh yth m ias th at p ersist for greater than
hem od ynam ically u nstable patients w ith large central clots. 24 h ou rs.
Available evid ence for p eriop erative p rop hylaxis to m onectom y. Lobectom y is typ ically feasible if the FEV1 is
prevent card iac arrhythm ias ind icates that a nu m ber of 60% p red icted or 1.5 L. Patients w ho d o not fu lfill these
antiarrhythm ic d ru gs have varying d egrees of efficacy. The criteria m ay be at an increased risk for p eriop erative d eath
cu rrent Am erican College of Chest Physician gu id elines and p u lm onary com p lications. In p atients w ith poor car-
recom m end using selective -blockers for AF risk red u c- d iop u lm onary reserves, su ch as those w ho w alk 25 shut-
tion (17). In cases w here -blockers are contraind icated , tles on tw o shu ttle w alks or less than one flight of stairs, are
am iod arone is recomm end ed . There is app rehension abou t at increased risk for p eriop erative d eath and card iopul-
the u se of am iod arone for prophylaxis becau se of the sm all m onary com p lications w ith stand ard lu ng resection, and
risk of acu te resp iratory d istress synd rome (ARDS) (19). should be cou nseled abou t nonstand ard surgery or nonop-
erative op tions (30).
■ Cardiac ischemia Aspiration
Etiology and Risk Factors The risk of aspiration increases w hen the airw ay is not p ro-
The risk of d evelop ing card iac ischem ia related to tho- tected , typ ically d u e to d ecreased m ental status second ary
racic su rgery varies accord ing to the p atient’s u nd erlying to comorbid cond ition (stroke, d em entia) or oversed ation.
card iac p erform ance. The risk of d evelop ing transient N arcotic m ed ications increase the risk of asp iration by
ischem ic ECG changes is 3.8% (20,21), ranging from 0.13% d ecreasing gastrointestinal m otility, w hich can lead to
in p atients w ith no p rior card iac history to betw een 2.8% vom iting, and oversed ation w ith lack of airw ay protection.
and 21% in p atients w ith p rior history of card iac infarc- Preventative m easu res includ e elevating the head of the
tion (21,22). The m ortality associated w ith p ostop erative bed , u se of ep id u rals to d ecrease narcotic requ irem ent, and
ischem ic event ranges betw een 2.3% and 70% (21,22). The attention to gastrointestinal sym p tom s inclu d ing abd om i-
onset of MI is u su ally on p ostop erative d ay 2 or 3. Abnor- nal d istension, nau sea, or constip ation. Treatm ent for aspi-
m al exercise tolerance test and intraop erative hyp otension ration inclu d es bronchoscop y w ith w ashing to rem ove
are the strongest p red ictors for p ostop erative ischem ic d ebris and collect cu ltu res, su p p lem ental oxygen, aggres-
events (20). sive p u lm onary p hysiotherap y, and antibiotics d irected by
cu ltu res.
Cardiopulmonary Risk Stratification
Sputum Retention
Intrathoracic surgery is considered an intermediate cardiac
risk procedure (23). The American College of Cardiology and Inability to breathe d eep ly or cou gh d ue to pain or overse-
the American Heart Association have published a guid eline d ation lead s to increased p ostop erative sp u tu m retention.
on perioperative cardiopulmonary risk assessment (24), Stagnation of secretions can resu lt in bronchial plu gging,
which reports increased perioperative cardiovascular com- atelectasis, lobar collap se, p neu m onia, and resp iratory fail-
plications in patients w ith active cardiac symptoms or car- ure. Current smokers, patients with COPD, stroke patients,
diac ischemia induced by low-level exercise. and those w ithou t regional analgesia are at increased risk
for sp u tu m retention (31). The valu e of p rop hylactic sm ok-
ing cessation im m ed iately p rior to su rgery is d ebated , bu t
■ Postoperative respiratory complications those w ho continu e to sm oke w ithin 1 m onth of pneu -
Resp iratory com plications occur in 10% to 20% of p atients m onectomy are at increased risk of d evelop ing p ostop era-
after lu ng resection and are a lead ing cau se of m ortality. In tive p neu m onia and ARDS (32).
a p rosp ective stu d y of 956 patients u nd ergoing resection
for N SCLC, the 30-d ay m ortality w as 12.5% higher in Postoperative Pneumonia
patients w ho d eveloped postoperative pu lm onary com p li- Postoperative pneumonia is a significant cause of morbid ity
cations than in those w ho d id not (25). Pu lm onary com p li- and mortality after major thoracic proced ures, w ith an inci-
cations encom p ass several entities, includ ing atelectasis, d ence of betw een 5.3% and 25% (7,33,34). Postoperative
pneu m onia, asp iration, and ARDS. The three m ost fre- pneumonia increases mortality by up to 26.3% after pul-
qu ently reported pred ictors for pu lm onary com plications m on ary resection (35). Risk factors associated w ith the
are low forced expired volum e in 1 second (FEV1), low d if- d evelop m ent of p ostop erative p neu m onia inclu d e p reop -
fu sing cap acity of lu ng for carbon m onoxid e (DLCO), and erative resp iratory infection, sp u tu m retention , a cu rrent
low p red icted p ostoperative DLCO (26–29). Other risk fac- sm oking habit, p oor m ental statu s, p oor p ain control,
tors inclu d e u nd ergoing pneum onectom y, neoad ju vant COPD, immunod eficiency, and postoperative ventilator
chem otherap y, and poor exercise tolerance. support. Pneumonias typically occur in early postoperative
course, accompanied by fever, elevated white blood cell
Pulmonary Risk Stratification count, and persistent infiltrate on chest radiograph, but may
All patients being consid ered for lung resection should be d ifficult to d iagnose because these are nonspecific find -
have sp irom etry testing. If the FEV1 is 80% pred icted or ings early after lung resection. The m ost comm on causative
2 L, and there is no evid ence of d yspnea on exertion or organisms are gram-negative rod s, Streptococcus pneumonia,
interstitial lu ng d isease, the patient is suitable for p neu - and Staphylococcus aureus (33,35). Broad-spectrum antibiotics
should be initiated in cases of suspected pneumonia and alveolar recru itm ent. Steroid therap y is recom mend ed by
adjusted on the basis of culture result. Prophylactic meas- som e bu t has not been u niversally u sed (43). A sm all series
ures to decrease pneumonia include smoking cessation, fou nd inhaled nitric oxid e u sefu l (44).
good pain control w ith epid ural catheter, chest physiother-
apy, incentive spirometry, and early ambulation. The routine
use of prophylactic antibiotics is not recommended. ■ Lobar torsion
■ Postresection pulmonary edema Lobar torsion is a rare bu t seriou s com p lication after lu ng
Etiology and Risk Factors resection. The incid ence is estimated at 0.1% to 0.3%. Right
m id d le lobe torsion after a right u p p er lobectom y accou nts
Pu lm onary ed em a is a d isastrou s com plication follow ing
for 70% of rep orted cases. Torsion of the bronchovascu lar
pulm onary resection. It is id entified u sing several term s
p ed icle results in strangu lation and airw ay obstru ction of
includ ing: noncard iogenic pu lm onary ed em a, acu te lu ng
the involved lobe. Com p lete interlobar fissu re and absence
injury (ALI), ARDS, and postp neum onectom y pu lm onary
of p arenchym al brid ge betw een contigu ou s lobes pred is-
ed em a. The synd rom e is characterized by acu te onset,
p ose to lobar torsion. Another p red isp osing factor that pro-
fluffy infiltrates on chest rad iograph, pu lm onary cap illary
m otes lobar m otility is atelectasis, and several lobar torsion
w ed ge p ressu re 18 mm H g, and PAO2/ FIO2 300 m m
cases have been rep orted in the setting of large p leu ral effu -
H g for ALI and 200 m m H g for ARDS. The m ortality rate
sion, p neu mothorax, or m ass effect from neop lasm (45,46).
for post resection p u lmonary ed em a is rep orted at 50% to
100%, and correlates w ith the extent of resection (36,37). Clinical Presentation
The incid ence of ARDS follow ing p u lm onary resection is
Pu lm onary torsion typically presents w ith an abru pt clini-
betw een 2.2% and 3.1% and also correlates w ith the extent
cal changes in p ost su rgical setting, w ith acu te onset of res-
of resection (36–38). It com plicates 4% to 16% of p neu -
p iratory d istress, acid osis, tachycard ia, loss of breath
monectom ies, bu t can also be seen at low er frequ encies fol-
sou nd s over the affected lu ng field , loss of air leak, shock,
low ing lobectom ies and VATS resections (36–38).
or sep sis. Rad iograp hic signs of torsion inclu d e: (a) lobe
Althou gh m any ind epend ent risk factors for ARDS
op acification, (b) change in location of an op acified lobe,
have been id entified , the inciting event is often unknow n
(c) hilar d isplacement, (d ) abnormal position of the pul-
(37–39). The m ost consistently reported risk factors are low
monary vasculature, (e) lobar air trapping, and (f) bronchial
FEV1, low DLCO, extent of lung resection, and excessive
cutoff or distortion (45). A CT scan is the best imaging
flu id ad m inistration (36,37,40–42). In a large prosp ective
mod ality to visu alize lobar torsion, bu t acqu isition d epend s
study of 1,428 patients undergoing lung resection, Alam et al.
on the p atient’s hem od ynam ic stability. Bronchoscopy is
found that the od d s ratio for d eveloping ALI w as 1.17 for
d iagnostic w ith the ap p earance of a d istorted or com -
every 500 m L incremental increase in p erioperative flu id
p ressed airw ay w ith a “fish m outh” ap pearance.
ad ministered (37).
Treatment and Prevention
Prevention of lobar torsion starts w ith a careful evalu ation
The p resentation of p ostresection p u lm onary ed em a can be
of the anatom ic lu ng p osition p rior to chest closu re. Staples
su btle in the initial stages w ith tachyp nea and low grad e
or su tu res are u sed to fixate a m obile lobe to a nearby lobe
tem p eratu re, bu t qu ickly p rogresses to p ulm onary ed em a,
(47). If the d iagnosis is m ad e p ostop eratively, im m ed iate
refractory hyp oxem ia, and hypercapnia. One-third of cases
re-exploration to restore the blood supp ly is p aram ount.
w ill begin w ithin 24 hou rs of su rgery, and m ost w ill mani-
Re-exp loration shou ld be w ithin 48 hou rs of the initial sur-
fest signs w ithin 3 d ays of su rgery, but onset has been
gery to avoid irreversible infarction (48). If viable at re-
reported as late as 7 d ays from resection. Once the process
exp loration, the torsed lobe shou ld be fixed in place to
is initiated , it p rogresses w ith rem arkable speed . Rad i-
p revent recu rrent torsion. If frankly gangrenou s, or if via-
ographic find ings typ ically lag by 24 hou rs. Differential
bility is in d ou bt, resection is ind icated . Broad -spectrum
d iagnosis inclu d es iatrogenic fluid overload , card iogenic
antibiotics shou ld be initiated u p on d iagnosis.
pulm onary ed em a, p u lm onary em bolu s, pneu m onia, and
aspiration. It is im p erative to consid er and exclud e these
etiologies prior to invoking the w orking d iagnosis of ■ Bronchial dehiscence/Bronchopleural fistula
postresection p u lm onary ed em a.
Treatment Bronchial stu m p d ehiscence is a breakd ow n of bronchial
Op tim al treatm ent rem ain s elu sive an d is su p p ortive in closu re after lu ng resection that lead s to a com m u nication
natu re. Therap y shou ld in clu d e intu bation and m ech an i- betw een the bronchu s and p leu ral sp ace, a bronchop leu ral
cal ventilation, d iu resis to im p rove flu id balance, broad - fistu la (BPF). It is a highly m orbid event, w ith incid ence
spectrum antibiotics coverage, bronchoscopy to remove any estim ated at 0.5% to 10% after p u lm onary resection and
bronchial plugs, and frequ ent p osition changes to maximize m ortality ranging from 25% to 71% (48). Bronchial stu m p
d ehiscences are d ivid ed into early and late, each w ith a chovascu lar fistu la, w here the bron ch ial stu m p su tu re
u niqu e set of risk factors. In general, early d ehiscence is lin e h as erod ed in to a n earby vascu lar stru ctu re. In late
secon d ary to p oor su rgical techniqu es. Late d ehiscence is cases of BPF, p atien ts can be m in im ally sym p tom atic,
u su ally related to ischem ia and p atient com orbid ities bu t m ay p resen t w ith fever, ch ills, an d ch ron ic cou gh
(49). Patient characteristics that p red isp ose to d eh iscen ce p rod u ctive of frothy and m u cop u ru lent secretion s sec-
inclu d e COPD, low FEV1, m alnu trition, d iabetes, steroid on d ary to p leu ral sp ace in fection . Th e p atien ts m ay also
u se, and n eoad ju van t th erap y. Su rgical factors that are d evelop a p referen ce for sleep in g w ith th e su rgical sid e
associated w ith increased risk for bronchial d ehiscence d ow n to p reven t leakage of p leu ral effu sion th rou gh th e
inclu d e right p neu m onectom y, resid u al neop lasm at the stu m p . Ch est rad iograp h u su ally d em on strate a fall in
bron ch ial m argin , extensive lym p h n od e d issection, th e flu id level or d evelop m en t of a n ew air/ flu id level
blood su p p lies interru p tion , stap led versu s h and sew n in th e ip silateral p leu ral sp ace (Fig. 25.1). Bron ch oscop y
closu re, long stu m p , or ten sion of th e closu re (48,50,51). is d iagn ostic.
The risk for d eveloping BPF follow ing right pneum onec-
tom y is 13.2%, versus 5% follow ing left pneu m onectom y Treatment and Prevention
(52). This d iscrep ancy is a d u e to intrinsic d ifferences in the Initial treatm ent for early BPF is p osition ing th e p atien t
blood su p p ly and soft tissue coverage. The right m ain stem in th e reverse Tren d elen bu rg w ith th e su rgical sid e
bronchu s is typically su pplied by a single bronchial artery, d ow n to m in im ize d rain age an d con tam in ation of th e
w hile the left is su pplied by tw o. The left m ain stem contralateral lu ng. A ch est tu be shou ld be p laced exp ed i-
bronchu s is em bed d ed in the richly vascu larized m ed iasti- tiou sly to evacu ate in fected flu id an d broad -sp ectru m
nal tissu e u nd er the aortic arch, w hile the right is freely an tibiotics in stitu ted . Early bron ch ial stu m p d eh iscen ce
exp osed in the p leural space. Positive pressure ventilation n eed s to be treated su rgically. Th e th oracic cavity shou ld
in the p ost op erative p eriod su bjects the bronchial stu m p to be exp lored the p leu ral sp ace d ebrid ed , and the bronchial
barotraum as and increases risk of stum p d ehiscence. stu m p insp ected . The stu m p length shou ld be assessed ,
and stu m p resected back if too long. Necrotic of devitalized
Clinical Presentation tissue should be debrided . Stu m p closu re is achieved w ith
Early bronchial stu m p d ehiscence occu rs w ithin the first interru p ted su tu res and reinforced w ith a vascu larized
few d ays to w eeks follow ing resection. Patients p resent p ed icle flap of p arietal p leu ral, p ericard ial fat, serratu s
w ith a large or p rolonged air leak or p rogressive su bcu ta- anterior, intercostal m u scle, or om entu m . Sm all BPF ( 5
neou s em p hysem a. Later in the p ostop erative cou rse, m m ) m ay be am enable to end oscop ic closu re w ith fibrin or
p atients m ay cou gh cop iou s am ou nt of clear or p u ru lent acrylic glu es w ith varying d egrees of su ccess. Sclerosis of
secretion second ary to d rainage of p leu ral flu id throu gh stu m p d ehiscence w ith N D:YAG laser or su bm u cosal injec-
the stu m p op ening. H em op tysis m ay herald an early bron- tions has also been rep orted (53–55).
FIGURE 25.1. Chest radiographs from patient who developed a bronchopleural fistula (BPF) two weeks after right pneumonec-
tomy. Radiograph on left is prior to discharge from hospital. The radiograph on right is 10 days later when patient presented with
fever, elevated white blood cell count and coughing up copious watery secretions, note the decrease in air fluid level consistent
with bronchial dehiscence.
Prevention of BPF starts w ith m itigating reversible risk Bronchoscopy should be done to evaluate the bronchial
factors and op tim izing of m ed ical and nu tritional statu s stu m p and to collect any flu id for bacterial cu ltu res. Thora-
preoperatively. In cases w here the patient is im m unocom - centesis is an im p ortant step and best d one u nd er u ltra-
promised , d iabetic, on steroid s, or has a history of neoad ju - sound guid ance because of the unpred ictably of the position
vant therap y, ad d itional operative m od ifications w ith of shifted intrathoracic organs after pneumonectom y (58).
ped icle flap s to bu ttress the stu m p shou ld be consid ered . Broad -spectrum antibiotics should be initiated immediately.
Stu mp ischem ia is prevented by avoid ing overzealous d is- The m ost com m on cau sative organism s are Staphylococcus
section. The length of the stum p shou ld be optim ally cre- aureus, Pseudomonas aeruginosa, or m u ltip le organ ism s
ated so as to avoid stagnation of secretion, and u nd u e (58,60,61).
tension at the su tu re line should be avoid ed . Postop erative
positive p ressu re ventilation should be avoid ed w henever Treatment and Prevention
possible. A chest tube w ithou t su ction shou ld be placed in the
infected cavity. Su rgical m anagem ent involves re-explo-
ration of infected sp ace, d rainage, w ashou t, d ebrid em ent,
■ Postresection empyema and exam ination of the bronchial stu m p . Once a fistula has
Etiology and Risk Factors been ru led ou t, m u ltip le op tions are available to clean
p leu ral sp ace, inclu d ing op en p acking via Elloesser flap or
By d efinition, p ostresection em p yem a is infection of the p leu ral w ind ow, m u ltip le su rgical d ebrid em ents, or p lace-
pleu ral sp ace after lu ng resection. Postresection em p yem a m ent of antibiotic irrigation system . Once the infection is
occu rs far m ore com m only after p neu m onectom y than controlled , and the p leu ral sp ace is cleaned , it can be
after lobectom y or lesser resections. Eighty percent of reclosed over antibiotic irrigation. There is a p au city of lit-
postpneu m onectom y em pyem a is associated w ith BPF eratu re on p ostresection em p yem a p rop hylaxis. Tw o stud -
(50,56,57). The m ortality associated w ith postpneu m onec- ies looked at intrap leu ral antibiotic irrigation and reported
tom y em p yem a is 30% to 40%, but d ecreases to 5% w ithou t a red u ction in the incid ence of em p yem as (62,63).
BPF (57). A retrosp ective stud y from the Mayo Clinic of 713
pneum onectom y p atients id entified factors associated w ith
increased risk for em p yem a inclu d ed : benign ind ication for
■ Persistent air leak
surgery, right p neu m onectom y, bronchial stu mp reinforce- Etiology and Risk Factors
ment, tim ing of chest tu be rem oval, low FEV1, low DLCO, Air leak is a condition where air enters into the pleural space
low p reop erative hem oglobin, and intraoperative and total throu gh an abnorm al com m unication from the airw ay or
am ount of blood transfusion. The risk of d evelop ing p ulmonary parenchyma. Air leaks rep resent one of the most
em p yem a is higher follow ing right p neu m onectom y than common complications after pulmonary resection. Most air
left becau se of higher risk BPF (56). Early em pyem a w ith- leaks heal sp ontaneou sly, bu t if a leak lasts for m ore than
out d ehiscence is thou ght to be cau sed by a d irect contam - 7 days, it is considered persistent. The incidence of persistent
ination of the p leu ral sp ace d uring surgery. Late em p yem a air leak ranges between 3% and 25% (2,64–66) and represents
d evelop s as a resu lt of hem atogenou s d issem ination from the most common reason for prolonged hospital stay follow-
sources su ch as d ental caries, pneu m onia, or append icitis. ing lung resection (66). Risk factors for persistent air leaks
include steroid use, malnutrition, diabetes, COPD, low FEV1,
Clinical Presentation male gend er, concomitant pneumothorax, pleural adhesions,
Postresection em p yem a can occu r at an y tim e in the up per lobectomy, and bilobectomy (66–68).
p ostop erative p eriod . Early em p yem a is u su ally d iag-
nosed w ith in 3 m on ths of su rgery an d rep resents 60% of Clinical Presentation
cases (58). Late p ostresection em p yem a is d iagn osed Postresection air leaks can be classified qu alitatively and
after 3 months of surgery, and can present as late as 40 years qu antitatively (68). Qu alitatively, air leaks are grou p ed by
after the resection. Patients m ay have nonsp ecific constitu - w hether they occu r d u ring insp iration, exp iration, or
tional sym p tom s su ch as fever, chills, or d ysp nea. Chest throu ghou t the resp iratory cycle. Continu ou s air leaks or
rad iograp h m ay show su btle changes ind icative of an those d u ring insp iration u su ally occu r in m echanically
early evolving em p yem a w ith shift in the m ed iastinu m ventilated p atients or those w ith a BPF. The grand m ajor-
aw ay from the op erative sid e. The m ed iastinu m p osition ity (98%) of p ost resection air leaks are exp iratory in
can also be affected by resp iratory p hases (59); insp iratory natu re, bu t can be su bd ivid ed based u p on their occu r-
film s are recom m end ed for p rop er assessm ent of the m ed i- rence w ith norm al exp iration or forced exp iration (68).
astinu m . An abru p t d ecrease in p leu ral flu id on the op era- The air leak m eter that com es w ith m ost m od ern p leu r-
tive sid e w ith constitu tional sym p tom s w ou ld ind icate evac d rainage system s can be u sed to qu alitatively m eas-
em p yem a w ith BPF as ou tlined above. Patients can p res- u re the leak. The m eters typ ically contain five to seven
ent w ith p u ru lent d rainage from the thoracotom y incision cham bers, w ith the first cham ber d enoting the sm allest
via p leu rocu taneou s fistu la, an entity know n as em p yem a leak (68). Serial evalu ation of air leak severity is im p ortant
necessitatis. to m onitor for im p rovem ent trend . As the lu ng heals, the
air leak classification w ill go from exp iratory to occu rring ascend s along the anterior vertebral colu m n betw een the
w ith forced exp iration only. Cerfolio has d em onstrated azygos vein and the aorta, p osterior to the esophagus. It
that p atients w ith large exp iratory leaks (extend ing into crosses the m ed iastinu m at the level of the carina and trav-
the last cham bers of the leak m onitor) in the im m ed iate els along the left sid e of the esophagus u ntil it exits the
p ostop erative p eriod are at increased risk for p ersistent m ed iastinu m and joins the ju nction of the left internal
air leaks, and m ay be best m anaged w ith early H eim lich ju gu lar and su bclavian veins in the neck. The thoracic d u ct
valve p lacem ent (69). is relatively w ell protected w ithin the p osterior m ed i-
astinu m bu t is at risk of inju ry d u ring com p licate card iac,
Treatment and Prevention aortic, esop hageal, p u lm onary, left cervical, and d iaphrag-
The treatm ent for air leaks is expectant, since alm ost all m atic op erations. Du ring rou tine resections for N SCLC, the
eventu ally heal. Tw o ind epend ent, rand om ized , p rosp ec- d u ct is m ost su scep tible to inju ry d u ring m ed iastinal
tive stu d ies for air leaks in p atients u nd ergoing elective lym ph nod e d issection in the su bcarinal and su baortic loca-
pu lm onary resection have reported that early placem ent of tions (74). The incid ence of chylothorax com p licating p ul-
chest tube to w ater seal lead s to shorter d uration of leak m onary resection is less than 1% in m ost series (75,76),
and d ecreases the tim e that the chest tu bes rem ain in p lace inclu d ing the recent ACOSOG series (2). Chylothoraces
(70,71). The tim ing of w ater seal w as d ifferent in these tw o occu r at a slightly higher rate follow ing right-sid ed p roce-
stu d ies. In one stu d y, tu bes w ere placed to w ater seal on d u res (75). The thoracic d u ct is the m ain cond uit for trans-
p ostop erative d ay 2 and in the other, im m ed iately after port of chyle from the intestine and lymphatics from the
surgery. A negative pressure intrathoracic environm ent lower extremities. Large thoracic duct leaks can result in fat
ind uced by suction stents opens areas of visceral pleu ral d epletion, d ehyd ration, hypoproteinemia, loss of fat-soluble
d isru p tion that im p ed es healing, and m ost likely exp lains vitam ins, and im m u nologic com p rom ise. Chyle is bacterio-
the su p eriority of w ater seal over su ction. A chest x-ray static w ith an alkaline p H and is an irritant w ithin the p leu -
shou ld be obtained w ithin 24 hou rs of placing a p atient ral sp ace w hen it leaks.
w ith an air leak to w ater seal to ensu re that there is no new
or enlarging p neu m othorax. Clinical Presentation
In a p atient w ith a persistent air leak, transition to ou t- There are typ ically 2 to 10 d ays betw een the d u ct inju ry
patient chest tu be m anagem ent should be m ad e w hile the and the d evelop m ent of a chylothorax. Chylothorax
patient is still hospitalized . A 24-hou r observation is u su - shou ld be su sp ected w hen there is rap id or excessive fill-
ally d one w ith the patient’s chest tu be connected to a ing of th e p leu ral sp ace follow ing a p neu m on ectom y or
H eim lich valve. If the chest x-ray d em onstrates no new excessive chest tu be d rainage follow ing lobectom y. Ch est
changes after 24 hours, then the patient can be safely d istu be ou tp u t 400 m L/ d ay, and esp ecially 700 m L/ d ay,
charged w ith the H eim lich valve and follow ed every one to is su ggestive of a chyle leak. Chyle is typ ically m ilky and
tw o w eeks in the clinic for chest tube rem oval (69). nonclotting, bu t m ay be clear in the fasting state. Triglyc-
Several intraop erative m easu res have been d evelop ed erid e concentrations greater than 110 m g/ d L, the presence
to m inim ize air leaks. A recent m eta-analysis of 16 clinical of chylom icrons, or a lym p hocyte level in the pleural flu id
trials com p aring stand ard closu re w ith or w ithou t sealant that is greater than that in the plasm a are d iagnostic of chy-
revealed that su rgical sealants red u ced p ostop erative air lothorax.
leaks and tim e to chest d rain rem oval, bu t d id not red u ce Lym p hangiograp hy can id entify the site and size of the
the length of p ostop erative stay (72). Another ap p roach is leak in 80% of cases (76,77). It can also d ifferentiate
creation of p leu ral tent, w hich involves mobilizing the ap i- betw een tributary inju ry and comp lete d u ct transection.
cal parietal pleu ra and d raping it on to the remaining lung, Unfortu nately, the p roced u re is technically challenging in
facilitating p leu ra-pleura apposition. This is p erform ed centers that d o not p erform it regu larly and u ncom fortable
after u p p er lobectom y, and efficacy w as rep orted in a for the p atient. CT scans are in general not helpfu l in d iag-
prosp ectively rand om ized trial of 200 patients w ho had nosis or w ork u p of thoracic d u ct inju ries.
und ergone elective u pper lobectom y (73).
■ Chylothorax Initial treatm ent of a chylothorax is ensu ring d rainage of
the chyle w ith a chest tu be, becau se chyle is irritating and
Etiology and Risk Factors lu ng re-exp ansion can help to seal the leak. Patients should
Chylothorax is the presence of lym phatic flu id in the pleu- be m ad e N PO (nothing by mouth) and parenteral nu trition
ral sp ace and is u su ally a resu lt of a leak from the thoracic started to d ecrease the chyle flow. Cessation of oral intake
d u ct or one of its tributaries. Operative inju ries are by far inhibits the absorp tion of fats and marked ly d im inishes
the m ost com m on cause of chylothorax. The anatom y of stim ulation of secretion into the gastrointestinal tract,
the thoracic d u ct is qu ite variable w ith the p rop ensity for d ecreasing the volu m e flow throu gh the thoracic d u ct and
mu ltip le med iastinal tru nks and crossing levels. In ap p rox- red u cing flu id , fat, and p rotein loss from the leak, w hile
im ately half of the p op u lation, it arises from the cisterna increasing the op p ortu nity for the d u ct to heal. Ap proxi-
chyli and enters the chest through the aortic hiatu s. It then m ately 50% of inju ries w ill resolve w ith these conservative
measu res (76,78). Som atostatin and its analogue octreotid e com p lication (84). Prim ary hyp eralgesia from exagger-
can be u sed w ith conservative m easures to sim ultaneou sly ated resp onse of local n ocicep tors to inflam m atory m ed i-
d ecrease the volum e of chyle d em onstrated utility in ani- ators, w h ich resu lts in p ain h yp ersensitization, is an other
mal stu d ies. There is no stand ard recom m end ation for how exp lanation for th is syn d rom e (85).
long to w ait for leak closu re. Most agree that the m axim u m
observation tim e is tw o w eeks and earlier intervention for Clinical Presentation
cases w here d rainage rem ains 500 m L/ d ay, or in p atients Presen tation for nerve inju ries d ep end s on th e nerve that
w ith severe nu tritional d eficits or evid ence of clinical d ete- w as inju red . Recu rren t laryn geal n erve inju ry lead s to
rioration is need ed (76,78–80). ip silateral vocal cord p aralysis, w ith a brassy or h oarse
Failure of conservative therapy w arrants su rgical inter- voice and an in creased risk for asp iration. Ph ren ic nerve
vention. The p rim ary goal of su rgery is to stop the leak. inju ries resu lt in u n ilateral d iap h ragm atic p aralysis.
This can be accom p lished by id entification and d irect lig- Chest x-ray m ay show elevation of d iap hragm , and flu o-
ation of th e leak or m ass by ligation of th e d u ct as it roscop y can be u sed to d em onstrate p arad oxical m ove-
enters the chest at the aortic hiatu s. Leak id entification is m ent of d iap hragm d u ring in sp iration . Phrenic nerve
facilitated by p reop erative lym p h an giograp hy or th e cond u ction stu d ies are available in a few sp ecialized cen-
ad m inistration of enteral fat in the form of cream of olive ters. Post-thoracotom y p ain synd rom e is u su ally d iag-
oil 2 or 3 hou rs p rior to su rgery. Tissu es arou nd the leak n osed at follow u p visits w ith u n resolved p ain and
are u su ally inflam ed an d requ ire p led getted su tu res for n eu ralgia in th e d istribu tion of the n erve, u su ally ante-
secu re closu re. Mass ligation involves su rrou nd ing and rior an d inferior to the thoracotom y.
tying all of the tissu e betw een the aorta, esop hagu s, and
azygos vein im m ed iately above the d iap hragm typ ically Treatment and Prevention
throu gh the right chest. In cases of right-sid ed leaks, the Treatm ent of recu rrent laryngeal nerve inju ries often
approach is straightforw ard . In left-sid ed chyle leaks, som e requ ires vocal cord m ed ialization to strengthen cou gh,
controversy exists as to w hich of the tw o approaches is im p rove voice qu ality and d ecrease the risk for asp iration.
more effective and from w hich sid e to proceed . Pleu rod esis Otolaryngologists frequ ently w ait 6 to 12 w eeks to d ifferen-
is ad vocated as com plim entary to either p roced ure. VATS tiate reversible from nonreversible inju ries. Treatm ent for
has becom e an attractive ap proach for treatm ent becau se it sym ptom atic phrenic nerve inju ries inclu d es d iaphragm
provid es excellent visualization of m ed iastinu m . p lication to help d ecrease the attenuation of the m u scle and
Pleural shunts and percutaneous thoracic d uct emboliza- red u ce atelectasis of the ad jacent lu ng. Phrenic nerve pac-
tion are alternatives to surgery. Embolization proced ures are ing typ ically requ ires an intact low er m otor neu ron, and is
increasing in use at selective centers w ith lymphangiogra- not ap p licable to p ost-thoracotom y inju ries. Currently
phy expertise, and are especially useful in cases of multiple there is no effect treatm ent to reverse the synd rom e, and
bilateral ducts which may escape mass ligation (77). gabap entin ap p ears to p rovid e the m ost significant sym p -
tom atic relief.
■ Nerve injuries
■ Postpneumonectomy syndrome
The incid ence for nerve inju ry d u ring thoracic su rgery is
1% (81). The risk for injury is influenced by the patient’s Postp neum onectom y synd rom e is a rare synd rom e d efined
anatom y, typ e of p roced u re, extent of resection, and su r- by a shift of the m ed iastinal stru ctu res into the ipsilateral
geon’s exp erience. N erves at risk of inju ry d u ring p u l- surgical sid e second ary to hyperinflation of the resid u al
monary resection inclu d e recu rrent laryngeal, phrenic, lu ng, resu lting in rotation and p rogressive airw ay obstru c-
vagu s, and intercostal. The recurrent laryngeal and vagus tion. An u nd erstand ing of the anatom ic changes that occur
nerves are at greatest risk during mediastinal surgery, includ- after p neu monectom y is help fu l in u nd erstand ing this syn-
ing cervical mediastinoscopy, thymectomy, esophagectomy, d rom e. The p ostp neu m onectom y sp ace u nd ergoes signifi-
thyroid surgery, and tracheostomy. Phrenic nerves are at cant rem od eling. It fills w ith sterile flu id over the first
greatest risk for injury during thymectomy, m ed iastinal several w eeks. The contralateral lu ng then slow ly becom es
lym p h nod e d issection for N SCLC, p ericard iotom y, or hyp erinflated , and shifts tow ard the p neu m onectom y sid e.
in trap ericard ial p n eu m on ectom y. In tercostal nerves can The accum u lated fluid in the pneu m onectom y is slow ly
be in ju red w ith an access in cision th rou gh th e ch est w all. reabsorbed w hile scar tissu e grow s to fill the sp ace. After
Post-thoracotom y p ain synd rom e is a w ell recogn ized right p neu m onectom y, the m ed iastinu m shifts to the right.
com p lication of thoracotom y w ith an incid ence betw een The heart and great vessels rotate cou nterclockw ise and
5% and 40% in VATS p atients an d 9% an d 80% in th oraco- can resu lt in com p ression of the left main stem betw een left
tom y p atients (82–87). It is d efined as p ersistent p ain p ulmonary artery and vertebral colum n or d escend ing
alon g a th oracotom y in cision for at least 2 m on th s after aorta. After left p neu m onectom y, the m ed iastinu m shifts to
the su rgery. Intercostal nerve d ysfu nction and entrap - the left, and the heart and great vessels rotate clockw ise
m ent are thou gh t to be cen tral in the d evelop m ent of th is w ith the potential to com press the airw ay betw een the
right p u lm onary artery and vertebral colu m n or aorta. The card iogenic shock. A high ind ex of suspicion and prompt
tw o largest rep orted cases series are both from Massachu - d iagnosis is crucial. Rad iographic find ings are characteristic
setts General H ospital w ith a com bined num ber of 29 and easily recognized . With right card iac herniation, the
patients (88,89). In their experience, postpneum onectom y heart is d isplaced to the m id line, a globu lar right card iac
synd rom e is m ore com m on after right p neu m onectom y, bord er visible in the right hemithorax (snow cone sign), and
occu rring in 68% of patients reported . The m ed ian tim e if a central line is present, a rotational kink at the level of the
betw een p neu m onectom y and presentation w as 7.5 years. right brachiocephalic venous junction. With left card iac her-
Postp neu m onectom y synd rom e is m ore likely to d evelop niation, the entire heart is in the left chest w ith a cleft
in infants and young child ren because of their anatom ic betw een the great vessels and the herniated chambers (93).
plasticity and increased lu ng com p liance.
Clinical Presentation Treatm ent of sym ptom atic card iac herniation requ ires
Patients are typ ically young and had und ergone p neu - im m ed iate reop eration to rep osition the heart. Prevention
monectom y in their child hood . Progressive d ebilitating of this d read fu l com p lication involves rep airing the peri-
d ysp nea is the hallm ark of the synd rom e. Dysphagia from card ial d efects at the tim e of resection. All large right-sid ed
d isp lacem ent of esophagus has also been reported . Patients p ericard ial d efects m ust be repaired because of the high
may also present w ith positional d yspnea from positional risk for d evelop ing herniation. The d efect m ay be closed
com p ression of the pulm onary veins (90). The w orku p p rim arily or w ith a p atch of p arietal p leu ral and prosthetic
inclu d es a p u lm onary fu nction test and chest im aging. A m aterials (21). Large left-sid ed d efects typ ically d o not
CT scan provid es the best inform ation on the d egree of requ ire rou tine closu re.
med iastinal shift and the anatom ical d etails. Other cau ses
of d ysp nea shou ld be ruled ou t, inclu d ing p u lm onary ■ Lung herniation
hyp ertension, congestive heart failure, d eclining p u l-
monary reserve, PE, or recu rrent cancer. Etiology and Risk Factors
There is a pau city of literatu re on lung herniation follow ing
Treatment and Prevention thoracotom y (95). Iatrogenic lu ng hernias, esp ecially inter-
N o p reventive m easu res are available, but several m ethod s costals lu ng hernias, are m ore frequ ently reported as a
have been d evised to surgically correct postp neum onec- com p lication of m inithoracotom ies or VATS. This is proba-
tom y synd rom e. The simp lest ap proach is placem ent of bly a result of less m eticu lou s closure of sm all incisions and
bronchial stents. This typically reserved for old er and m ore the typ ical lack of closure of intercostal d efects d uring
d ebilitated patients because of the risk of stent m igration VATS (96,97). Other risk factors associated w ith lu ng her-
and erosion in younger patients. The more invasive niation inclu d e steroid u se, d iabetes, obesity, increased
app roach involves re-exp loration of the pneu m onectom y intrathoracic pressure, and lung volum e from positive pres-
site, lysis of ad hesions, and placem ent of saline p rosthesis sure ventilation or em physema, rib resection, or repeat tho-
to anatom ically correct the m ed iastinal shift. This resu lts in racotomy/ thoracostomy (98,99). H ow ever, patients w ho
an im p rovem ent in sym ptom s in a significant nu m ber of have had large chest w all resections w ithout reconstruction
patients (88). Su ccessfu l VATS approaches for the treatm ent or have gaps in the intersp ace betw een paracostal sutu res
have also been reported (91,92). from thoracotomy d o not routinely d evelop hernia (100).
■ Cardiac herniation
Sym p tom s related to lu ng herniation are vagu e. Patients
Etiology and Risk Factors p resent w ith interm ittent bulging in the chest w all that
Card iac h erniation occu rs w hen th e heart m igrates m ay or m ay not be tend er. Carefu l p alp ation of the incision
throu gh a d efect in the p ericard iu m , rotating along its axis site w ith p atient cou ghing elicits a soft, elastic bu lge. Lung
and lead ing to volvu lu s. It is a rare com p lication associ- herniation can be d iagnosed d efinitively w ith chest CT.
ated w ith a 40% to 60% m ortality rate in recognized cases
and 100% in u nd iagnosed cases (93,94). H erniation of the Treatment and Prevention
heart occu rs w hen the p ericard iu m has been op ened , as Prevention starts w ith meticulous w ound closure, especially
w ith p artial p ericard ectom y, intrap ericard ial pneu m onec- at the pericostal level. Med ical and nutritional optimizations
tom y, or intrap ericard ial ligation of pulm onary vessels. are important to promote w ound healing. Lung hernias, like
other hernias, are at risk for incarceration or strangulation,
Clinical Presentation and should be repaired if these signs are present. N umerous
The onset is usually w ithin hours of surgery accompanying repair methods have been reported, including reapproxima-
alterations in intrathoracic pressu re. It can be triggered by tion of defect w ith pericostal heavy nylon sutures or w ires,
applying su ction on the chest tu be, coughing, or bod y p osi- coverage with prosthetic material, or coverage w ith muscle
tional change (21,94). Patients d evelop hemod ynam ic insta- flaps or omentum. VATS techniques have been successfully
bility w ith elevated central venou s p ressure suggestive of used to repair lung herniation (96,97,101).
■ COMPLICATIONS RELATED TO flu id . A w ou nd infection m ay also p resent w ith ind u ration,

bu t ap p ear erythem atou s, is tend er to the tou ch, and has
CHEST WALL RESECTION
p u ru lent d rainage from the su rgical site and constitu tional
Malignancy, infection, radiation injury, or any combinations sym p tom s.
of the three are the most common indication for chest wall
resection. Resections for malignancy are performed for pri- Treatment and Prevention
mary chest wall malignancies, metastatic spread from distant The m anagem ent of serom a is conservative since the risk
sites, or for d irect extension from NSCLC or breast cancer. of infection is low. Serom as typ ically resp ond to rep eated
The tenets of chest w all resection and reconstruction are (a) d rainage. In contrast, w ou nd infection is a d read ed com -
removal of all malignant or d evitalized tissue, (b) restoration p lication in the setting of chest w all resection becau se the
of rigidity to large chest wall defects to prevent flail chest, p otential to sp read to intrathoracic sp ace. Early m anage-
and (c) healthy soft tissue coverage to seal the pleural space, m ent involves antibiotics therap y and rem oval of infected
protect underling organs, and prevent infection. Appropriate p rosthesis. Infection frequ ently resu lts in significant
planning is required prior to the start of surgery, to ensure ind u ration and fibrosis of u nd erling tissu e and therefore
that adequate margins are obtained, while necessary muscles rem oval of p rosthetics d oes not typ ically resu lt in flail
and soft tissues need ed for reconstruction are preserved . chest. Mu scu locu taneou s or om entu m flap w ith skin graft
can be u sed for reconstru ction w hen infection is con-
■ Flail chest and respiratory complications trolled . Prosthetic m aterials shou ld not be u sed in an infec-
tiou s setting.
Etiology and Risk Factors Vacu u m -assisted closu re (VAC) technology has p roven
Chest w all d efects greater than 4 cm or from resection of to be a very effective tool in the m anagem ent of com p lex
three or m ore contigu ou s ribs have the p otential to resu lt in chest w all w ou nd s. Su batm osp heric p ressu re d ressings
a flail chest w ith p arad oxical m ovem ent of the chest w all are now com m ercially available as the VAC d evice (KCI,
d u ring resp iration, lead ing to resp iratory com prom ise. San Antonio, TX) (106). Vacu u m -assisted closu re d evices
Mu ltivariate analysis of com p lications after chest w all accelerate w ou nd healing by m aintaining an op tim al envi-
resection id entified d efect size as the m ost significant p re- ronm ent w ith su batm osp heric p ressu re at ap p roxim ately
d ictor of com p lication (102). Respiratory com plication is 125 m m H g w ith an alternating cycle of 5 m inu tes of su c-
the m ost com m on com p lication w ith an estim ated inci- tion follow ed by 2 m inu tes off su ction. Su batm osp heric
d ence of 11% to 20% (103–105). Respiratory failu re is the p ressu re also alters the cytoskeleton of the cells in the
most com mon cau se of postop erative m ortality (102,103). w ou nd bed , and triggers a cascad e of intracellu lar signals
that increase cell d ivision and su bsequ ent form ation of
Clinical Presentation granu lation tissu e (107). These effects m ake the VAC
Patients typically present with respiratory failure in immedi- d evice an extrem ely versatile tool in the w ou nd healing
ate postoperative setting secondary to flail chest. Mechanical arm am entariu m .
ventilation may be required for respiratory insufficiency.
Treatment and Prevention ■ Scapula entrapment

Intraop erative restoration of chest w all rigid ity w ith p ros- Etiology and Risk Factors
thetic m aterials su ch as, polytetrafluoroethylene (PTFE) Posterior d efects on the su p erior asp ect of the chest w all
patch, m ethyl methacrylate sand w ich, or autologou s tissu e u su ally d o not need closu re becau se of coverage by
such as fascia lata red u ces this com plication. The choice of scap u la. H ow ever, if the d efect extend s p ast the fou rth rib
prosthetic m aterial for chest w all reconstru ction m ostly the scap u la tip s can get trap p ed in the d efect d u ring
d epend s on surgeon preference. m ovem ent.
■ Wound complications: seroma
Patient p resents w ith p ain and inability to m ove their
and wound infection
ip silateral u p p er extrem ity or w ith p ainfu l catch ing w ith
Etiology and Risk Factors m ovem ent.
Wou nd com plications are the second m ost com mon post-
op erative comp lications associated w ith chest w all resec- Treatment and Prevention
tion, occu rring in 7% to 18% of cases (103–105). Fortu nately, Intraoperative reconstru ction of large posterior chest w all
serom a is m ore com m on than w ou nd infection. d efects and those that extend beyond the fou rth rib should
avoid this com p lication. Re-exp loration throu gh the initial
Clinical Presentation thoracotom y and patch reconstru ction is w arranted w hen
A painless soft tissue ind uration w ith no erythem a is usu- this p resents p ostop eratively, bu t scarring can m ake it far
ally a serom a. Asp iration of the ind u ration returns serou s m ore challenging than initial reconstru ction.
■ CONCLUSION 21. Karam ichalis JM, Pu tnam JB Jr, Lam bright ES. Card iovascu lar com p li-
cations after lu ng su rgery. Thorac Surg Clin 2006;16(3):253–260.
22. H errington CS, Shu m w ay SJ. Myocard ial ischem ia and infarction
Lu ng cancer is the lead ing cause of cancer-related d eath in postthoracotom y. Chest Surg Clin N Am 1998;8(3):495–502, vii.
the United States. Lu ng resection w ith and w ithou t chest 23. Fleisher LA, Beckm an JA, Brow n KA, et al. 2009 ACCF/ AH A Focu sed
w all resection p resents su rgical and p ostop erative chal- Upd ate On Perioperative Beta Blockad e incorporated into the
ACC/ AH A 2007 Guid elines on Periop erative Card iovascu lar Evalu a-
lenges d ue to the frail natu re of the N SCLC pop ulation. tion and Care for N oncard iac Su rgery: a rep ort of the Am erican Col-
Rigorou s p reop erative assessm ent, m eticu lou s attention to lege of Card iology Found ation/ Am erican H eart Association Task
operative techniqu e, and vigilance in postop erative care Force on Practice Gu id elines. Circulation 2009;120(21):e169–e276.
24. Fleisher LA, Bass EB, McKeow n P. Method ological ap p roach: Am eri-
w ill continu e to ad vance the practice, d ecrease com p lica- can College of Chest Physicians Gu id elines for the Prevention and
tions, and im p rove outcom es for this com m on m alignancy. Managem ent of postoperative atrial fibrillation after Card iac Surgery.
Chest 2005;128(2, Su p pl):17S–23S.
25. Am ar D, Mu noz D, Shi W, et al. A clinical p red iction ru le for p u l-
■ REFERENCES m onary com p lications after thoracic su rgery for p rim ary lu ng cancer.
Anesth Analg 2010;110(5):1343–1348.
1. Jem al A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J 26. Bru nelli A, Refai M, Salati M, et al. Pred icted versu s observed FEV1
Clin 2009;59(4):225–249. and DLCO after m ajor lu ng resection: a p rosp ective evalu ation at d if-
2. Allen MS, Darling GE, Pechet TT, et al. Morbid ity and m ortality of ferent postop erative period s. Ann Thorac Surg 2007;83(3):1134–1139.
m ajor pu lm onary resections in patients w ith early-stage lung cancer: 27. Brunelli A, Ferguson MK, Rocco G, et al. A scoring system predicting the
initial results of the rand om ized , p rosp ective ACOSOG Z0030 trial. risk for intensive care unit admission for complications after major lung
Ann Thorac Surg 2006;81(3):1013–1019; d iscu ssion 1019–1020. resection: a multicenter analysis. Ann Thorac Surg 2008;86(1):213–218.
3. Strand TE, Rostad H , Dam hu is RA, et al. Risk factors for 30-d ay m or- 28. Ferguson MK, Du rkin AE. A com p arison of three scoring system s for
tality after resection of lung cancer and pred iction of their m agnitud e. pred icting com plications after m ajor lu ng resection. Eur J Cardiothorac
Thorax 2007;62(11):991–997. Surg 2003;23(1):35–42.
4. Licker MJ, Wid ikker I, Robert J, et al. Op erative m ortality and resp ira- 29. Ferguson MK, Gaissert H A, Grab JD, et al. Pu lm onary com p lications
tory com plications after lung resection for cancer: im p act of chronic after lu ng resection in the absence of chronic obstructive pu lm onary
obstructive pu lm onary d isease and tim e trend s. Ann Thorac Surg d isease: the p red ictive role of d iffu sing cap acity [p u blished online
2006;81(5):1830–1837. ahead of p rint Septem ber 26, 2009]. J Thorac Cardiovasc Surg
5. Dom inguez-Ventu ra A, Allen MS, Cassivi SD, et al. Lu ng cancer in 2009;138(6):1297–1302. DOI: 10.1016/ j.jtcvs.2009.05.045.
octogenarians: factors affecting m orbid ity and m ortality after p u l- 30. Bru nelli A, Belard inelli R, Refai M, et al. Peak oxygen consu m p tion
m onary resection. Ann Thorac Surg 2006;82(4):1175–1179. d u ring card iop u lm onary exercise test im p roves risk stratification in
6. Litle VR, Sw anson SJ. Postop erative bleed ing: coagu lop athy, bleed - cand id ates to m ajor lu ng resection [pu blished online ahead of print
ing, hem othorax. Thorac Surg Clin 2006;16(3):203–207, v. N ovem ber 24, 2008]. Chest 2009;135(5):1260–1267. DOI: 10.1378/ chest.
7. H arp ole DH Jr, DeCam p MM Jr, Daley J, et al. Prognostic m od els of 08-2059.
thirty-d ay m ortality and m orbid ity after m ajor p u lm onary resection. 31. Bond e P, McManu s K, McAnesp ie M, et al. Lu ng su rgery: id entifying
J Thorac Cardiovasc Surg 1999;117(5):969–979. the su bgrou p at risk for sp u tu m retention. Eur J Cardiothorac Surg
8. Dod d oli C, Thom as P, Thirion X, et al. Postop erative com p lications in 2002;22(1):18–22.
relation w ith ind u ction therap y for lu ng cancer. Eur J Cardiothorac 32. Vap orciyan AA, Merrim an KW, Ece F, et al. Incid ence of m ajor p u l-
Surg 2001;20(2):385–390. m onary m orbid ity after pneum onectom y: association w ith tim ing of
9. Sakuragi T, Sakao Y, Fu ru kaw a K, et al. Su ccessfu l m anagem ent of sm oking cessation. Ann Thorac Surg 2002;73(2):420–425; d iscu ssion
acute p ulm onary em bolism after su rgery for lu ng cancer. Eur J Cardio- 425–426.
thorac Surg 2003;24(4):580–587. 33. Schu ssler O, Alifano M, Derm ine H , et al. Postop erative p neu m onia
10. Patel A, Anraku M, Darling GE, et al. Venou s throm boem bolism in after m ajor lung resection. Am J Respir Crit Care Med 2006;173(10):
patients receiving m u ltim od ality therap y for thoracic m alignancies. 1161–1169.
J Thorac Cardiovasc Surg 2009;138(4):843–848. 34. Du qu e JL, Ram os G, Castrod eza J, et al. Early com p lications in su rgi-
11. Ziom ek S, Read RC, Tobler H G, et al. Throm boem bolism in p atients cal treatm ent of lung cancer: a p rosp ective, m u lticenter stu d y. Gru p o
u n d ergoing th oracotom y. Ann Thorac Surg 1993;56(2):223–226; d is- Coop erativo d e Carcinom a Broncogenico d e la Socied ad Esp anola d e
cu ssion 227. N eu m ologia y Ciru gia Toracica. Ann Thorac Surg 1997;63(4):944–950.
12. Amar D. Prevention and m anagement of perioperative arrhythmias in 35. Rad u DM, Jau regu y F, Segu in A, et al. Postop erative p neu m onia after
the thoracic surgical population. Anesthesiol Clin 2008;26(2):325–335, vii. m ajor pulm onary resections: an u nsolved problem in thoracic sur-
13. De Decker K, Jorens PG, Van Schil P. Card iac com p lications after non- gery. Ann Thorac Surg 2007;84(5):1669–1673.
card iac thoracic su rgery: an evid ence-based cu rrent review. Ann Tho- 36. Du lu A, Pastores SM, Park B, et al. Prevalence and m ortality of acu te
rac Surg 2003;75(4):1340–1348. lung inju ry and ARDS after lu ng resection. Chest 2006;130(1):73–78.
14. Park BJ, Zh ang H , Ru sch VW, et al. Vid eo-assisted th oracic su rgery 37. Alam N , Park BJ, Wilton A, et al. Incid ence and risk factors for lu ng
d oes not red u ce the in cid ence of p ostop erative atrial fibrillation inju ry after lu ng cancer resection. Ann Thorac Surg 2007;84(4):
after p u lm onary lobectom y. J Thorac Cardiovasc Surg 2007;133(3): 1085–1091; d iscu ssion 1091.
775–779. 38. Ruffini E, Parola A, Papalia E, et al. Frequ ency and m ortality of acu te
15. Cresw ell LL, Schu essler RB, Rosenbloom M, et al. H azard s of postop - lung injury and acu te respiratory d istress synd rom e after pulm onary
erative atrial arrhythm ias. Ann Thorac Surg 1993;56(3):539–549. resection for bronchogenic carcinoma. Eur J Cardiothorac Surg 2001;20(1):
16. Am ar D, Goenka A, Zhang H , et al. Leu kocytosis and increased risk of 30–36, d iscu ssion 36–37.
atrial fibrillation after general thoracic su rgery. Ann Thorac Surg 39. Roberts JR. Postop erative resp iratory failu re. Thorac Surg Clin
2006;82(3):1057–1061. 2006;16(3):235–241, vi.
17. McKeow n PP, Gu tterm an D. Execu tive su m m ary: Am erican College 40. Ku tlu CA, William s EA, Evans TW, et al. Acu te lu ng inju ry and acu te
of Chest Physicians guid elines for the prevention and m anagem ent of respiratory d istress synd rom e after p u lm onary resection. Ann Thorac
postoperative atrial fibrillation after card iac su rgery. Chest 2005;128(2, Surg 2000;69(2):376–380.
Su ppl):1S–5S. 41. Licker M, d e Perrot M, H ohn L, et al. Periop erative m ortality and
18. Lee JK, Klein GJ, Krahn AD, et al. Rate-control versu s conversion m ajor card io-pu lm onary com plications after lung surgery for non-
strategy in postop erative atrial fibrillation: a p rosp ective, rand om ized sm all cell carcinom a. Eur J Cardiothorac Surg 1999;15(3):314–319.
pilot stud y. Am Heart J 2000;140(6):871–877. 42. Parqu in F, Marchal M, Mehiri S, et al. Post-p neu m onectom y p u l-
19. Van Mieghem W, Coolen L, Malysse I, et al. Am iod arone and the m onary ed em a: analysis and risk factors. Eur J Cardiothorac Surg
d evelopm ent of ARDS after lu ng su rgery. Chest 1994;105(6):1642–1645. 1996;10(11):929–932; d iscu ssion 933.
20. von Knorring J, Lep antalo M, Lind gren L, et al. Card iac arrhythm ias 43. Steinberg KP, H ud son LD, Good m an RB, et al. Efficacy and safety of
and m yocard ial ischem ia after thoracotom y for lu ng cancer. Ann Tho- corticosteroids for persistent acute respiratory distress syndrome. N Engl
rac Surg 1992;53(4):642–647. J Med 2006;354(16):1671–1684.
44. Mathisen DJ, Ku o EY, H ahn C, et al. Inhaled nitric oxid e for ad u lt res- 71. Marshall MB, Deeb ME, Bleier JI, et al. Su ction vs w ater seal after p u l-
piratory d istress synd rom e after p u lm onary resection. Ann Thorac m onary resection: a rand om ized p rosp ective stu d y. Chest 2002;
Surg 1998;66(6):1894–1902. 121(3):831–835.
45. Felson B. Lu ng torsion: rad iograp hic find ings in nine cases. Radiology 72. Beld a-Sanchis J, Serra-Mitjans M, Iglesias Sentis M, et al. Su rgical
1987;162(3):631–638. sealant for p reventing air leaks after p u lm onary resections in p atients
46. Ohd e Y, N akagaw a K, Oku m u ra T, et al. Sp ontaneou s p u lm onary tor- w ith lu ng cancer. Cochrane Database Syst Rev 2010;(1):CD003051.
sion second ary to pseu d o-Meigs’ synd rom e. Interact Cardiovasc Thorac 73. Bru nelli A, Al Refai M, Monteverd e M, et al. Pleu ral tent after u p p er
Surg 2005;4(1):59–60. lobectom y: a rand om ized stu d y of efficacy and d u ration of effect. Ann
47. H igashiyam a M, Takam i K, H igaki N , et al. Pu lm onary m id d le lobe Thorac Surg 2002;74(6):1958–1962.
fixation u sing TachoCom b in p atients u nd ergoing right u p p er lobec- 74. H an iu d a M, N ish im u ra H , Kobayashi O, et al. Man agem ent of ch y-
tom y w ith com plete obliqu e fissu re. Interact Cardiovasc Thorac Surg lothorax after p u lm onary resection . J Am Coll Surg 1995;180(5):
2004;3(1):107–109. 537–540.
48. Farkas EA, Detterbeck FC. Airw ay com p lications after p u lm onary 75. Le Pim p ec-Barthes F, D’Attellis N , Du jon A, et al. Chylothorax com -
resection. Thorac Surg Clin 2006;16(3):243–251. plicating p u lm onary resection. Ann Thorac Surg 2002;73(6):1714–1719.
49. Jichen QV, Chen G, Jiang G, et al. Risk factor com p arison and clinical 76. Cerfolio RJ, Allen MS, Descham p s C, et al. Postop erative chylothorax.
analysis of early and late bronchop leu ral fistu la after non-sm all cell J Thorac Cardiovasc Surg 1996;112(5):1361–1365; d iscu ssion 1365–1366.
lu ng cancer su rgery. Ann Thorac Surg 2009;88(5):1589–1593. 77. Cop e C, Salem R, Kaiser LR. Managem ent of chylothorax by p ercu ta-
50. Abbas Ael S, Descham p s C. Postp neu m onectom y em p yem a. Curr neou s catheterization and em bolization of the thoracic d u ct: p rosp ec-
Opin Pulm Med 2002;8(4):327–333. tive trial. J Vasc Interv Radiol 1999;10(9):1248–1254.
51. Liberm an M, Cassivi SD. Bronchial stu m p d ehiscence: u p d ate on pre- 78. Shim izu K, Yoshid a J, N ishim u ra M, et al. Treatm ent strategy for chy-
vention and m anagem ent. Semin Thorac Cardiovasc Surg 2007;19(4): lothorax after p ulm onary resection and lym ph nod e d issection for
366–373. lung cancer. J Thorac Cardiovasc Surg 2002;124(3):499–502.
52. Darling GE, Abd u rahm an A, Yi QL, et al. Risk of a right p neu m onec- 79. Gu illem P, Pap achristos I, Peillon C, et al. Etilefrine u se in the m an-
tom y: role of bronchop leu ral fistu la. Ann Thorac Surg 2005;79(2): agem ent of p ost-operative chyle leaks in thoracic su rgery. Interact Car-
433–437. diovasc Thorac Surg 2004;3(1):156–160.
53. Kanno R, Su zuki H , Fu jiu K, et al. End oscop ic closu re of bron- 80. Patterson GA, Tod d TR, Delaru e N C, et al. Su p rad iap hragm atic liga-
chop leu ral fistu la after p neu m onectom y by su bm u cosal injection of tion of the thoracic d u ct in intractable chylou s fistu la. Ann Thorac Surg
polid ocanol. Jpn J Thorac Cardiovasc Surg 2002;50(1):30–33. 1981;32(1):44–49.
54. Kiriyam a M, Fujii Y, Yam akaw a Y, et al. End obronchial neod ym ium : 81. Krasna MJ, Forti G. N erve inju ry: inju ry to the recu rrent laryngeal,
yttriu m -alu m inu m garnet laser for noninvasive closu re of sm all p rox- phrenic, vagu s, long thoracic, and sym p athetic nerves d u ring thoracic
im al bronchop leu ral fistu la after lu ng resection. Ann Thorac Surg su rgery. Thorac Surg Clin 2006;16(3):267–275, vi.
2002;73(3):945–948; d iscu ssion 948–949. 82. Gotod a Y, Kam bara N , Sakai T, et al. The m orbid ity, tim e cou rse and
55. Wang KP, Schaeffer L, H eitm iller R, et al. N d :YAG laser closu re pred ictive factors for p ersistent p ost-thoracotom y p ain. Eur J Pain
of a bronchop leu ral fistu la. Monaldi Arch Chest Dis 1993;48(4): 2001;5(1):89–96.
301–303. 83. Allam a AM. Intercostal m u scle flap for d ecreasing p ain after thoraco-
56. Descham ps C, Bernard A, N ichols FC III, et al. Em p yem a and bron- tom y: a p rosp ective rand om ized trial. Ann Thorac Surg 2010;89(1):
chopleu ral fistula after p neu m onectom y: factors affecting incid ence. 195–199.
Ann Thorac Surg 2001;72(1):243–247; d iscu ssion 248. 84. Magu ire MF, Latter JA, Mahajan R, et al. A stu d y exp loring the role of
57. Gharagozloo F, Margolis M, Facktor M, et al. Postp neu m onectom y intercostal nerve d am age in chronic p ain after thoracic su rgery. Eur J
and p ostlobectom y em p yem a. Thorac Surg Clin 2006;16(3):215–222. Cardiothorac Surg 2006;29(6):873–879.
58. Kopec SE, Irw in RS, Um ali-Torres CB, et al. The p ostp neu m onectom y 85. Koehler RP, Keenan RJ. Managem ent of p ostthoracotom y p ain: acu te
state. Chest 1998;114(4):1158–1184. and chronic. Thorac Surg Clin 2006;16(3):287–297.
59. Wechsler RJ, Good m an LR. Med iastinal p osition and air-flu id height 86. Perttu nen K, Tasm u th T, Kalso E. Chronic p ain after thoracic su rgery:
after p neu m onectom y: the effect of the resp iratory cycle. AJR Am J a follow -up stu d y. Acta Anaesthesiol Scand 1999;43(5):563–567.
Roentgenol 1985;145(6):1173–1176. 87. Dajczm an E, Gord on A, Kreism an H , et al. Long-term p ostthoraco-
60. Pairolero PC, Arnold PG, Trastek VF, et al. Postp neu m onectom y tom y p ain. Chest 1991;99(2):270–274.
em p yem a. The role of intrathoracic m u scle transp osition. J Thorac Car- 88. Shen KR, Wain JC, Wright CD, et al. Postp neu m onectom y synd rom e:
diovasc Surg 1990;99(6):958–966; d iscu ssion 966–958. su rgical m anagem ent and long-term resu lts. J Thorac Cardiovasc Surg
61. Zu m bro GL Jr, Treasu re R, Geiger JP, et al. Em p yem a after p neu - 2008;135(6):1210–1216; d iscu ssion 1216–1219.
m onectom y. Ann Thorac Surg 1973;15(6):615–621. 89. Grillo H C, Shep ard JA, Mathisen DJ, et al. Postp neu m onectom y syn-
62. Miller JD, N em ni J, Sim one C, et al. Prop hylactic intracavitary (p neu - drome: diagnosis, management, and results. Ann Thorac Surg 1992;54(4):
m onectom y sp ace) antibiotic instillation: a com p arative stu d y. Ann 638–650; d iscu ssion 650–631.
Thorac Cardiovasc Surg 2001;7(1):14–16. 90. Partington SL, Graham A, Weeks SG. Pu lm onary vein stenosis follow -
63. Gold straw P. Prop hylaxis of p ostp neu m onectom y em p yem a. Thorax ing left p neu m onectom y: a variant contributor to postpneum onec-
1980;35(2):107–110. tom y synd rom e. Chest 2010;137(1):205–206.
64. Stolz AJ, Schu tzner J, Lischke R, et al. Pred ictors of p rolonged air leak 91. N g T, Ryd er BA, Maziak DE, et al. Thoracoscop ic ap p roach for the
follow ing p u lm onary lobectom y. Eur J Cardiothorac Surg 2005;27(2): treatm ent of p ostp neu m onectom y synd rom e. Ann Thorac Surg 2009;
334–336. 88(3):1015–1018.
65. Isow a N , H asegaw a S, Band o T, et al. Preop erative risk factors for pro- 92. Reed MF, Lew is JD. Thoracoscop ic m ed iastinal rep ositionin g for
longed air leak follow ing lobectom y or segm entectom y for prim ary p ostp neu m onectom y synd rom e. J Thorac Cardiovasc Surg 2007;133(1):
lu ng cancer. Eur J Cardiothorac Surg 2002;21(5):951. 264–265.
66. Abolhod a A, Liu D, Brooks A, et al. Prolonged air leak follow ing rad i- 93. Mehanna MJ, Israel GM, Katigbak M, et al. Card iac herniation after
cal upp er lobectom y: an analysis of incid ence and possible risk fac- right pneu m onectom y: case rep ort and review of the literatu re. J Tho-
tors. Chest 1998;113(6):1507–1510. rac Imaging 2007;22(3):280–282.
67. Bru nelli A, Fianchini A, Al Refai M, et al. Internal com p arative au d it 94. Rod enw ald t J, Lem bcke AE, Wiese TH , et al. Postop erative d islocation
in a thoracic su rgery u nit using the physiological and operative sever- of the heart after pneum onectom y. Circulation 2002;105(7):e49–e50.
ity score for the enum eration of m ortality and m orbid ity (POSSUM). 95. DiMarco AF, Oca O, Renston JP. Lu ng herniation. A cau se of chronic
Eur J Cardiothorac Surg 2001;19(6):924–928. chest p ain follow ing thoracotom y. Chest 1995;107(3):877–879.
68. Cerfolio RJ. Recent ad vances in the treatm ent of air leaks. Curr Opin 96. Berry MF, Fried berg J. Chest w all/ d iap hragm atic com p lications. Tho-
Pulm Med 2005;11(4):319–323. rac Surg Clin 2006;16(3):277–285, vii.
69. Cerfolio RJ, Bass CS, Pask AH , et al. Pred ictors and treatm ent of p er- 97. Weissberg D, Refaely Y. H ernia of the lu ng. Ann Thorac Surg
sistent air leaks. Ann Thorac Surg 2002;73(6):1727–1730; d iscussion 2002;74(6):1963–1966.
1730–1721. 98. Van Den Broeck S, Van Rom p aey V, Ortm anns P, et al. Intercostal lu ng
70. Cerfolio RJ, Bass C, Katholi CR. Prosp ective rand om ized trial com - herniation after rep eat thoracotom y. Minerva Chir 2008;63(4):307–310.
p ares su ction versus w ater seal for air leaks. Ann Thorac Surg 2001; 99. Moncad a R, Vad e A, Gim enez C, et al. Congenital and acqu ired lu ng
71(5):1613–1617. hernias. J Thorac Imaging 1996;11(1):75–82.
100. Tem es RT, Talbot WA, Green DP, et al. H erniation of the lu ng after 104. Mansou r KA, Thou rani VH , Losken A, et al. Chest w all resections and
vid eo-assisted thoracic su rgery. Ann Thorac Surg 2001;72(2):606–607. reconstru ction: a 25-year exp erience. Ann Thorac Surg 2002;73(6):
101. Santini M, Fiorello A, Vicid om ini G, et al. Pu lm onary h ern ia sec- 1720–1725; d iscu ssion 1725–1726.
ond ary to lim ited access for m itral valve su rgery an d rep aired by 105. Descham p s C, Tirnaksiz BM, Darband i R, et al. Early and long-term
vid eo thoracoscop ic su rgery. Interact Cardiovasc Thorac Surg 2009;8(1): resu lts of p rosthetic chest w all reconstru ction. J Thorac Cardiovasc Surg
111–113. 1999;117(3):588–591; d iscu ssion 591–582.
102. Weyant MJ, Bains MS, Venkatram an E, et al. Resu lts of chest w all 106. Welvaart WN , Oosterhu is JW, Pau l MA. N egative p ressu re d ressing
resection and reconstru ction w ith and w ithou t rigid p rosthesis. Ann for rad iation-associated w ou nd d ehiscence after posterolateral thora-
Thorac Surg 2006;81(1):279–285. cotom y. Interact Cardiovasc Thorac Surg 2009;8(5):558–559.
103. Lans TE, van d er Pol C, Wou ters MW, et al. Com p lications in w ound 107. Saxena V, H w ang CW, H u ang S, et al. Vacu u m -assisted closu re:
healing after chest w all resection in cancer patients; a m ultivariate m icrod eform ations of w ou nd s and cell p roliferation. Plast Reconstr
analysis of 220 p atients. J Thorac Oncol 2009;4(5):639–643. Surg 2004;114(5):1086–1096; d iscu ssion 1097–1088.
CHAPTER
26
Complications of
Extracorporeal Circulation
J ennifer S. Lawton
■ INTRODUCTION ■ MECHANISMS
Extracorp oreal circu lation is a form of tem p orary circu la- Fortu nately, m ost p atients w ho u nd ergo CPB recover w ith-
tory su p p ort that is nonp hysiologic and u su ally nonp u l- ou t significant com p lication. The m echanism s responsible
satile. This form of circu latory su p p ort m ay or m ay not for inju ry m ay inclu d e any of the follow ing: a generalized
inclu d e an inline oxygenator. Extracorp oreal circu lation low flow state, relative ischem ia and rep erfu sion inju ry,
m ay be u sed to p rovid e hem od ynam ic su p p ort, gas exp osu re to anticoagu lation and its reversal, hem od ilu tion
exchange, or bod y tem p eratu re regu lation. Extracorp oreal and the d estru ction of the blood constitu ents, the em boliza-
circu lation, in the form of card iop u lm onary byp ass (CPB), tion of gas or p articu late m atter, the p lacem ent of intravas-
allow s for the p erform ance of card iothoracic su rgery in a cu lar cannu lae, m ishap s related to p u m p s and tu bing, and
qu iet, blood less field . This chap ter focu ses on CPB as it is the activation of a system ic inflam m atory resp onse. Com -
u sed for the p erform ance of card iothoracic su rgery. p lications d irectly related to the CPB m achine m ay inclu d e
Extracorp oreal circu lation w as first u sed to p erform the p ow er interru p tion, air introd u ction via p hysical jarring of
intracard iac repair of an atrial septal d efect by John Gibbon the m achine or circu it m anip u lation, oxygenator failu re,
on May 6, 1953 (1). Technologic ad vances since that tim e d islod gem ent of a connection, p u m p head reversal, tubing
have m ad e CPB read ily available and technically feasible, ru p tu re, im p rop er occlu sion, and stop cock d islod gem ent
w ith a su bsequ ent d ecline in the m orbid ity and m ortality or tu rning. Com p lications second ary to CPB are grouped
of card iothoracic su rgery. Unfortunately, the use of CPB accord ing to organ system , w ith emp hasis on p athophysi-
requ ires system ic anticoagu lation and introd u ces the blood ology, risk factors, p revention, and management. This chap-
to nonend othelial surfaces that result in d etrimental changes ter w ill focu s on ad u lt patients only.
evid ent throu ghou t the bod y. These d etrim ental changes
resu lt in p ostop erative com p lications that increase m orbid -
ity, m ortality, and the cost and length of hosp italization for
■ CARDIOVASCULAR COMPLICATIONS
patients u nd ergoing card iothoracic su rgery. Inju ry to the heart d uring CPB m ay be m anifested as poor
In a series of 10,634 patients, investigators reported that m yocard ial fu nction at the tim e of sep aration from bypass.
15% of p atients having coronary artery bypass grafting had Myocard ial d ysfu nction attribu ted to CPB alone is often
one or m ore com p lications, and those patients w ho had d ifficu lt to d istingu ish from d ysfu nction as a resu lt of p re-
com plications experienced an eightfold to tenfold increase existing inju ry or d am age d u e to p oor m yocard ial p rotec-
in op erative m ortality (2). Althou gh it is u ncertain w hat tion. Myocard ial d ysfu nction follow ing CPB that im proves
portion of p ostop erative com plications can be attributed to after a lim ited tim e is called m yocard ial stu nning. Myocar-
CPB alone, it is clear that p rolonged CPB tim e is a signifi- d ial stu nning is a reversible p ostischem ic contractile d ys-
cant risk factor for all p ostoperative com plications. The fu nction that p ersists after rep erfu sion d esp ite the absence
com plications of CPB have com e u nd er intense interest and of irreversible d am age and d esp ite the retu rn of norm al
critical scru tiny recently d u e to the m ore w id esp read ad ap- p erfu sion (4). Stu nning occu rs in u p to 10% of p atients and
tation of off-p u m p coronary artery bypass grafting and the is associated w ith m ortality as high as 17% (1,5). Myocar-
d evelop m ent of m inim ally invasive techniqu es. The u se of d ial stu nning attribu ted to CPB m ay resu lt from flu id
off-p u m p techniqu es to avoid the com p lications associated overload and ed em a, activation of com p lem ent and neu -
w ith CPB seem s intu itively beneficial. H ow ever, large, trop hils, m icroem boli, d am age to the coronary end othe-
prospective rand om ized trials have yet to d eterm ine the liu m by card iop legic arrest and rep erfu sion, inad equ ate
actu al benefits of p erform ing surgery w ithout CPB (3). protection d uring aortic cross clamping, and global ischemia
and rep erfu sion (1,6).
Injury to the heart structures during CPB may occur. Epi-
Jennifer S. Lawton: Washington University School of cardial vessels can be injured w ith manipulation of the heart.
Med icine, 660 S. Eu clid Ave., St. Lou is, MO 63110 The coronary sinus may be perforated d ue to the placement
290
Chapter 26 • Complications of Extracorporeal Circulation 291
of a retrograd e card ioplegia catheter, the left ventricle m ay increased interstitial ed em a and atelectasis, increased vas-
be p erforated d u e to the placem ent of a left ventricu lar cu lar p erm eability, d ecreased colloid osm otic p ressu re d ue
vent, and the sinus nod e m ay be inju red second ary to to hem od ilu tion, bronchosp asm , and d ecreased su rfactant
pu rse-string su tu res or retraction. p rod u ction (1,9,11).
CPB also con tribu tes to p ostop erative arrhythm ias, Du ring CPB the lu ngs rem ain in an altered state of
inclu d ing su p raventricu lar tachycard ia, atrial fibrilla- d eflation, w hich contribu tes to atelectasis. The d iaphragm
tion, ventricu lar tachycard ia, and heart block. The altered becom es p assively d isp laced cep halad by the abd om inal
electrolyte balance follow ing ischem ia, card iop legia contents in the p aralyzed p atient. Deflation, com bined
ad m inistration , and rep erfu sion m ay p lay a role in this w ith p referential ventilation to the nond ep end ent regions
com p lication. The etiology of arrhythm ias is m u ltifactorial of the lu ng, lead s to ventilation-p erfu sion m ism atch (11).
and m ay inclu d e inflam m ation second ary to su rgical The lu ngs receive blood largely from the bronchial arteries,
trau m a and manipulation, intracoronary air em bolism , ele- as p u lm onary artery blood flow m ay be m inim al, con-
vated catecholam ine levels, and ischem ic injury (7,8). tribu ting to p u lm onary ischem ia d u ring CPB (10,12). The
Vascu lar com p lications of CPB m ay inclu d e the d irect sequ estration of neu trop hils in the lu ng m icrovascu latu re
inju ry to a vessel w all second ary to cannu la p lacem ent, resu lts in the release of oxygen free rad icals and p roteolytic
aortic d issection or p osterior aortic w all p erforation sec- enzymes with resultant edema and increased capillary per-
ond ary to cannu la p lacem ent, or em bolization of p articu - meability (1). A cycle of poor gas exchange, increased pul-
late m atter. The p lacem ent of intravascu lar cannu lae can monary vascular resistance, increased capillary permeability,
also resu lt in retrop eritoneal hematoma, vessel transection, and more edema ensues.
and ischemia or m alp erfu sion of the low er extremity.
Risk factors associated w ith card iovascular com plica-
tions follow ing CPB inclu d e p erip heral vascu lar d isease,
■ Risk factors
em ergency su rgery, presence of unstable angina, length of Risk factors associated w ith p u lm on ary d ysfu nction fol-
CPB, and p oor p reoperative ventricular fu nction. low in g CPB inclu d e d u ration of CPB, ad van ced age,
elevated pu lm onary artery p ressure, p oor p reop erative pu l-
monary function, tobacco use, chronic bronchitis, obesity,
■ Prevention p reop erative pulmonary ed ema, p oor ventricular function,
Strategies to p revent card iovascu lar com p lications inclu d e history of cerebrovascu lar d isease, and emergency surgery
frequ ent and com plete d elivery of card ioplegia, com p lete (9,13).
coronary revascu larization w hen p ossible, m inim ization of
byp ass tim e, the u se of epiaortic u ltrasound to gu id e can-
nu la p lacem ent, and confirm ation of cannu lae p lacem ent
■ Prevention
using transesop hageal echocard iography, pressu re w ave- Strategies that m inim ize lung injury follow ing CPB inclu d e
form s, or p u lsatility. Myocard ial d ysfunction follow ing limiting the d uration of CPB, use of leukocyte filters, contin-
CPB m ay be m u ltifactorial and challenging to treat. A p u l- u ou s hemofiltration w hile on CPB, preventing low colloid
monary artery catheter is often helpfu l in d ecision m aking. osmotic pressu re w ith albumin p riming, and venting the
Card iac ou tpu t should be op tim ized by the m anipu lation left heart if pu lmonary artery pressu res are elevated (9,10).
of p reload , heart rate, contractility, and afterload . Technical The ad m inistration of a series of sighs or slow, su s-
problem s related to the surgery shou ld be exclu d ed u sing tained breaths p rior to reinflation of the lu ngs, and separa-
echocard iograp hy, the assessm ent of coronary graft flow tion from CPB im p roves ventilation to atelectatic segm ents
using u ltrasou nd , or card iac catheterization. Stu nned (11). Su p p ort of the p atient w ith significant lu ng inju ry fol-
myocard ium that d oes not respond to m aximu m inotrope low ing CPB inclu d es p ositive p ressu re ventilation, d iu resis
d oses m ay be supp orted by u sing an intra-aortic balloon w hen ap p rop riate, hem od ynam ic su p p ort, and , occasion-
pu m p (IABP) and , u ltim ately, a ventricular assist d evice. ally, extracorp oreal m em brane oxygenation. Pharm aco-
Postop erative arrhythm ias are typically treated by tem - logic m anip u lations have not p roven u sefu l in lim iting
porary p acing or by pharm acologic treatm ent. Blood vessel p ostop erative lu ng inju ry (10). Large, rand om ized trials of
inju ry or transection requ ires operative repair, and an iatro- off-p u m p byp ass su rgery com p ared to on-p um p su rgery
genic aortic d issection requires rep lacem ent of the ascend - m ay elu cid ate the role of CPB in lu ng inju ry. An isolated
ing aorta to re-establish the norm al aortic lum en. role m ay be d ifficult to elicit d ue to the ad d itional d eleteri-
ou s p u lm onary effects related to general anesthesia and
sternotom y.
■ PULMONARY COMPLICATIONS
Lu ng inju ry is the m ost com m on seriou s injury follow ing
CPB (9). Lu ng injury m ay range from m inor su bclinical
■ IMMUNE AND ALLERGIC COMPLICATIONS
fu nctional changes to ad u lt respiratory d istress synd rom e Mechanical shear stress, contact w ith the nonend othelial
(10). Lu ng in ju ry is d u e to m any factors, inclu d in g surfaces of the CPB circu it and the w ou nd , and the form a-
leu koem bolization second ary to com plem ent activation, tion of heparin-p rotam ine com plexes lead to the activation
Table 2 6 .1 In fl a m m a t or y m ed ia t or s a n d m ech a n ism s of in ju r y d u r in g

ca r d iop u lm on a r y byp a ss
Mediator Effects
Complement: anaphylatoxins Increased vascular permeability
C3a, C4a, C5a Histamine release from mast cells and basophils
Smooth muscle contraction
Leukocyte migration
Cytokine release
Neutrophils and mast cell enzyme release
C3a-caused platelet aggregation
C5a-caused neutrophil aggregation and adherence to endothelium
Cytokines: TNF- , IL-6, IL-8, IL-10 Altered myocardial contractility
Chemoattraction of neutrophils
IL-10 may be protective
Arachidonic acid metabolites Thromboxane A2-caused vasoconstriction, platelet aggregation
Prostaglandins (E1, E2, I2)-caused vasodilatation, platelet antiaggregant
Leukotriene-caused chemoattractant, increased vascular permeability
Clotting and fibrinolytic systems/ Bradykinin leads to vasodilatation, smooth muscle contraction
kallikrein–bradykinin system Increased vascular permeability
Kallikrein activates plasminogen to plasmin
Endothelial cells facilitate plasminogen activation
Endotoxin (intestinal mucosa) Activation of complement
Increased release of cytokines
TNF, tumor necrosis factor.
of the plasma enzyme systems and formed elements of ■ PROTAMINE REACTION

blood (1). This reaction is called the w hole bod y inflamma-
tory response or cascad e. The magnitud e of the inflamma- Protam ine is u tilized to reverse the system ic anticoagula-
tory response has been d emonstrated to ad versely influence tion effects of hep arin follow ing cessation of CPB. Du ring
clinical ou tcome follow ing CPB (14). Red uced levels of reac- p rotam ine ad m inistration, p atients m ay exp erience a range
tive med iators have been d emonstrated w ith off-pump of reactions from hyp otension to a severe catastrophic reac-
byp ass surgery, bu t it is u nclear how this red uction trans- tion. A severe p rotam ine reaction lead s to m assive pu l-
lates to clinical benefit (15–17). Activation of m u ltip le m ed i- m onary vasoconstriction, system ic hyp otension, and right
ators by CPB u ltimately lead s to tissu e d amage and organ heart failu re.
inju ry. These m ed iators, their sites of origin, and the m echa- Previou s exp osu re to p rotam ine, fish allergy, d iabetes
nism s of inju ry are sum m arized in Table 26.1 (1,9,18). m ellitu s, and exp osu re to p rotam ine-containing insu lin
have been im p licated as risk factors for p rotam ine reaction.
Previou s exp osu re is the m ost im p ortant p red ictor (24–27).
■ Risk factors H yp otension m ay be avoid ed by the slow ad m inistra-
tion of protam ine and by the ad m inistration of vasopres-
Length of CPB is key in the d egree of inflam m atory reac-
sors. The often fatal id iosyncratic reaction that inclu d es
tion invoked and is correlated w ith m ed iator and cytokine
hyp otension, bronchosp asm , p u lmonary vasoconstriction,
levels.
and right heart failu re is typ ically refractory to m ed ical
therapy and often requires reheparinization and reinstitu -
■ Prevention tion of CPB for hem od ynam ic su p p ort. Therap y m ay then
inclu d e p u lm onary vasod ilators, system ic vasoconstric-
Strategies to lim it the inflam m atory resp onse to CPB tion, steroid s, antihistam ines, and am inop hylline (28).
includ e leu kocyte filtration, u ltrafiltration, heparin-bond ed
circuits, anticytokine antibod ies, and steroid s (1,19–22).
These m ethod s have typ ically targeted only one sp ecific
■ HEPARIN-INDUCED THROMBOCYTOPENIA
portion of this com p licated process and therefore have not H ep arin is requ ired to p revent throm bosis of the CPB cir-
consistently benefited patient ou tcom e. Large, prosp ective cu it. H ep arin-ind u ced throm bocytop enia resu lts from the
rand om ized clinical trials are need ed to establish the clini- p rod uction of im m u noglobu lin G antibod ies that recognize
cal benefit of m any of these strategies (18,23). p latelet factor 4 w hen bou nd to hep arin (29). This reaction
lead s to platelet activation and to activation of the coagu la- Table 2 6 .2 Tr ea t m en t of bleed in g follow in g
tion cascad e. Patients d evelop throm bosis w hich m ay lead ca rd iop u lm on a r y byp a ss
to lim b am p u tation and d eath. The p resence of antibod y is
associated w ith a significant increase in m orbid ity and Correct abnormal laboratory values:
mortality (30,31). Platelet transfusion
H ep arin exp osu re is essential for the d evelop m ent of Cryoprecipitate administration
heparin-induced thrombocytopenia. Unfractionated heparin Fresh frozen plasma administration
Additional protamine
from porcine intestinal m u cosa is preferred over heparin
obtained from bovine lu ng d u e to its red u ced risk of anti- Correct hypothermia:
bod y form ation (29). Prevention of heparin-ind u ced Use a blood product warmer for massive transfusions
throm bocytop enia m ay be facilitated by the lim ited u se of Warm the patient with a topical warming device
hep arin to only su rgical proced u res requiring its use and Avoid systemic hypertension that places tension on suture lines
reliance on other alternatives for p reop erative and p ostop - Administer supplemental protamine dose to treat heparin rebound
erative antithrom botic prophylaxis and therap y (32).
Avoid hemodilution and support blood volume and hemodynamics with
The d iagnosis of hep arin-ind u ced throm bocytop enia packed red blood cell transfusion when appropriate
mu st be consid ered w hen throm bocytopenia occurs fol-
Increase positive end-expiratory pressure on ventilator
low ing CPB. If the d iagnosis is su spected , all hep arin
shou ld be im m ed iately d iscontinued . Ad m inistration of Consider desmopressin or epsilon-aminocaproic acid
throm bin inhibitors is essential in the p revention of throm - Maintain a high suspicion of tamponade if cardiac output decreases,
botic com p lications related to heparin-ind u ced throm bocy- chest tube output decreases, and CVP increases
top enia. Direct throm bin inhibitors lepiru d in, bivaliru d in, Surgical exploration if bleeding remains excessive
or argatroban are recom mend ed , w ith the choice d ep end -
ing on renal and hepatic function (29). CVP, central venous pressure.
■ HEMATOLOGIC COMPLICATIONS ■ Risk factors

The interaction of blood w ith air and w ith the nonend othe- Factors that resu lt in an increased risk of bleed ing follow ing
lial surface of the CPB circu it resu lts in a m yriad of effects CPB inclu d e red o surgery, su rgery requiring hypothermia
on the hem atologic system . Postoperative bleed ing requ ir- below 27ºC, p reop erative u se of aspirin or anticoagulants,
ing retu rn to the operating room occurs in up to 5% of significant liver d isease or congestion, end stage renal d is-
patients (9). The m ost d read ed hem atologic com p lication is ease, and congenital or acqu ired coagu lation p rotein d efi-
clotting of the oxygenator or the CPB circu it. The most ciency (1,9,35,36). Prolonged CPB time is also a risk factor
com m on com p lication p ertaining to hem ostasis is d u e to for postoperative hematologic complications (37).
qu alitative an d qu an titative p latelet d efects. Platelets are
d ilu ted an d d estroyed d u rin g CPB an d are often d efec-
tive d u e to p reop erative m ed ications su ch as asp irin, ■ Prevention
d ip yrid am ole, and clop id ogrel. Mu ltip le strategies may be em p loyed to p revent hem ato-
A variety of events contribu te to the hem atologic com - logic com p lications follow ing CPB. The antifibrinolytics
plications follow ing CPB. Coagu lation factors are hem od i- epsilon-am inocaproic acid and tranexam ic acid m ay be
luted by the p u mp p rim e. The fibrinolytic system is u sed to red u ce m ed iastinal blood loss and transfu sion
activated follow ing contact of factor XII w ith the circu it requ irem ents (35). Maintenance of a hem atocrit level 22%
and by stim u lation of end othelial cells. Throm bin is gener- d u ring CPB w ill significantly red u ce the incid ence of post-
ated by the coagu lation cascad e. A system ic d ose of op erative bleed ing and m orbid ity and m ay imp rove long-
hep arin is ad m inistered to prevent throm bosis of the cir- term su rvival (38). Controlled , gentle card iotom y su ction
cu it. Card iotom y and vent su ctions result in tu rbu lence d ecreases shear forces and p reserves p latelets (36). Rep le-
and shear stress of the blood elements, w hile p latelet tion of antithrombin III by the ad ministration of fresh frozen
aggregation lead s to im paired function. Platelet fu nction is plasm a corrects hep arin resistance. Ad d itional d oses of
fu rther inhibited by hypotherm ia (1,9,33). H ep arin resist- p rotamine are effective in treating hep arin rebou nd . The
ance is d u e to antithrom bin III d epletion preop eratively by treatment of bleeding following CPB begins w ith the investi-
hep arin therap y, resulting in the need for increased d oses gation of causative factors. A management strategy is sum-
of hep arin to achieve ad equ ate activated clotting tim e lev- marized in Table 26.2 (39).
els for CPB as w ell as the need for antithrom bin III reple-
tion. H ep arin rebou nd is d efined as p ersistence of active,
unm etabolized heparin follow ing the ad m inistration and
■ ENDOCRINE COMPLICATIONS
com p lete m etabolism of protamine. Both hep arin resist- Pain, stress, hyp otherm ia, hem od ilu tion, and the contact of
ance and rebou nd m ay contribu te to p ostoperative bleed - blood w ith a nonend othelial su rface lead to physiologic
ing (1,34). resp onses d u ring CPB. Mu ltip le changes are noted in
end ogenou s horm one levels d esp ite their relative lack of renal d ysfu nction, age 70 years, d iabetes m ellitu s, blood
physiologic control d uring CPB. H em od ilu tion resu lts in a transfu sion, p reviou s card iac su rgery, congestive heart fail-
d ecrease in total and ionized calciu m , parathyroid hor- u re, u se of IABP, u nstable angina, low card iac ou tput,
mone, T3, and T4 (9,40). H yp erglycem ia is noted d u ring em ergency su rgery, and d u ration of CPB (9,45–47).
CPB second ary to d ecreased insu lin secretion, d ecreased
perip heral glu cose u tilization second ary to hypotherm ia,
and elevated levels of circu lating cortisol and epinep hrine
■ Prevention
(9,33,41). Increased levels of norep inephrine, ald osterone, Strategies to p revent renal failure focus u pon the preven-
renin, angiotensin, and vasopressin are noted . There is an tion of oligu ria by m axim izing card iac outpu t and u tilizing
increase in free fatty acid s and lipid m etabolism . Decreased d iu retic therap y, the lim itation of CPB tim e, m aintenance of
levels of atrial natriu retic factor and ad renocorticotropin an alkaline u rine if hem olysis is ongoing, and the avoid -
horm one are noted d uring CPB (33,41). ance of nep hrotoxic d ru gs or d yes. Consid eration shou ld
Many of the horm onal changes noted are inevitable be given to d elaying surgery follow ing the ad m inistration
d u ring CPB and are lim ited only by the length of CPB. of nep hrotoxic agents su ch as card iac catheterization.
Increasing the d ep th of anesthesia d u ring CPB or p rovid - Strategies to m anage renal inju ry are based on the m ain-
ing pulsatile perfusion may blunt some hormonal responses. tenance of flu id and electrolyte balance and the use of
The significance of horm onal resp onses on u ltim ate ou t- hem od ialysis w hen ind icated . H em od ilu tion w ith a crys-
com e is u nknow n (41). talloid prim e solution and hyperglycem ia provid e m od est
d iu resis in m ost p atients follow ing CPB. Flu id losses
■ FLUID BALANCE AND RENAL COMPLICATIONS shou ld be rep leted and p reload m axim ized . Often the m ost
im p ortant strategy in the p ostop erative p eriod is the
Du ring CPB the intravascu lar volu m e of the bod y is im p rovem ent of card iac ou tp u t w ith resu lting im p roved
rem oved , hem od ilu ted , and then retu rned . The norm al renal p erfusion.
physiologic resp onses to intravascu lar volu m e change are
elim inated d u ring CPB as central venou s pressu re is artifi-
cially controlled . The ad u lt patient may gain 1 to 15 lb (u p
■ CENTRAL NERVOUS SYSTEM
to 6.8 kg) follow ing CPB; the am ount of w eight gained
COMPLICATIONS
increases w ith the length of CPB (33). Fluid accum u lation Significant neu rologic inju ry is the m ost d isabling of all
occurs m ainly in the extracellu lar, extravascular interstitial com p lications relating to CPB. Central nervou s system
space (42). Renal im p airm ent is observed in 12% of p atients (CN S) inju ry ranges from m inor cognitive d eficit to overt
follow ing CPB, and the incid ence of renal failu re requ iring stroke. Inju ry m ay inclu d e d eliriu m , encep halop athy, con-
hem od ialysis is ap p roxim ately 1% to 5% (9,43). Renal fail- fu sion, agitation, d isorientation, d row siness, d ecreased
ure follow ing CPB resu lts in an eightfold increase in m or- alertness, m em ory d eficit, seizu re, or other neu ropsychi-
bid ity and m ortality. Mortality rates increase 20-fold in atric d istu rbances (48).
patients w ho requ ire hem od ialysis (43,44). N eurologic d eficits are often d ifficu lt to quantify and
Renal insu fficiency m ay be attribu ted to a com bination categorize. Many stud ies have und erestimated the number
of hemod ilution, low perfusion pressure and d ecreased of patients w ith d eficits becau se find ings may be su btle and
renal blood flow on CPB, hypothermia, microembolization, d ifficult to d ocum ent (49,50). The incid ence of stroke fol-
circulating hormones (renin, ald osterone, vasopressin, and low ing CPB ranges from 1% to 7% (51,52). The incid ence of
angiotensin II) that cause renal vasoconstriction, injury sec- encephalopathy is as high as 7% (53), and u p to 53% of
ond ary to inflammatory med iators, and hemolysis (1,9). p atients und ergoing card iac surgery experience p ostopera-
Despite the beneficial effects of increased blood flow second - tive cognitive d eficits (54,55). N eu rologic inju ry is p articu -
ary to decreased viscosity, the hemodilution of CPB results larly d evastating because it significantly increases mortality,
in fluid retention as a d ecrease in plasma colloid osmotic length of hospital stay, and cost of hospitalization and
pressure leads to increased capillary permeability and requires inpatient and ou tpatient rehabilitation (49,53).
vasodilatation (33,42). Hypothermia reduces glom erular fil- N eu rologic inju ry is attribu ted to global or regional
tration, renal blood flow, and osmolar clearance (42). Ald os- hyp op erfu sion, hem orrhage, or em bolic p henom enon.
terone and vasopressin prom ote conservation of sod ium Global hyp op erfu sion is p articu larly im p ortant in p atients
and water and renal vasoconstriction (42). Hemolysis results w ith hyp ertension w ho requ ire a higher m ean arterial
in hemoglobin cast formation in renal tubules (33,42). p ressu re d u ring CPB to p rovid e ad equ ate blood flow to
the brain. The p resence of significant carotid artery d is-
ease increases this risk, p articu larly in the region of the
■ Risk factors
brain at risk.
Factors that are pred ictive of postop erative flu id accu m ula- The nu m ber of cerebral em boli d etected d u ring CPB
tion inclu d e obesity, fem ale sex, d iabetes m ellitu s, em er- has been correlated w ith the d egree of neu rologic d eficit
gency su rgery, ad vanced age, congestive heart failu re, and p ostop eratively (56). Em bolic p henom ena m ay occu r as a
preoperative anem ia (33,42). Risk factors associated w ith resu lt of cannu lation of the aorta, clam p ing the aorta,
renal d ysfu nction follow ing CPB inclu d e p reop erative intracard iac d ebris or clot, or gaseou s or p articu late m atter
from the card iotom y suction and the CPB m achine (33,57). Table 2 6 .4 Strategies to m in im ize n eu rologic
Air em boli m ay resu lt from the reversal or kinking of in ju ry du rin g cardiopu lm on a ry bypass
pu m p or vent lines, the vortexing of air entering an em p ty
venou s reservoir, air entry around vent lines, an intra- Address symptomatic carotid artery stenosis preoperatively
venou s infu sion line in a p atient w ith a p atent foram en Image ascending aorta using epiaortic ultrasound probe to guide
ovale or sep tal d efect, the clotting or d etachm ent of the cannulation site
oxygenator, inad equ ate d eairing of open card iac cham bers, Plan “no touch” technique for calcified aorta
a break in the integrity of the arterial line, and the introd u c-
Minimize frequency of aortic cross clamping
tion of air bu bbles in solu tion into the internal m am m ary
artery graft lu m en (58). Careful deairing maneuvers: vent aorta and use Trendelenburg position
Microembolization m ay includ e gas, lipid particles, when removing cross clamp
atheroma, calcific d ebris, bone marrow, glove pow d er, Maintain adequate mean arterial pressure
aggregates of blood cells or fibrin, or particles of silicone or Minimize cardiotomy suction
polyvinyl chloride tubing (9,59). Using transcranial Doppler
Perform careful and thorough debridement and irrigation of intracardiac
ultrasonograp hy, CPB has been d em onstrated to signifi-
debris
cantly increase the number of microemboli compared to the
use of off-p ump coronary artery bypass techniqu es (60–62). Minimize cardiopulmonary bypass and deep hypothermic circulatory
arrest time
The number of microemboli has been d emonstrated to
increase significantly w ith perfusionist m anipu lations su ch Consider retrograde cerebral perfusion during circulatory arrest
as injection of d ru gs into the CPB circuit or the acquisition Adhere to cooling and warming guidelines to prevent air precipitation
of blood samples from the circuit (63).
■ Risk factors m itral valve, the u se of off-p u m p coronary artery byp ass
Risk factors for stroke in p atients und ergoing CPB are su m - techniqu es w ith p lacem ent of p roxim al anastom oses on
marized in Table 26.3 (49,64,65). Technical strategies m ay internal m am m ary artery grafts, rep lacem ent of the entire
be em p loyed to red u ce neu rologic injury d u ring CPB ascend ing aorta, and the p lacem ent of p roxim al anasto-
(Table 26.4). Prior to cannu lation, care should be given to m oses on the d escend ing aorta. Other strategies includ e the
the site of cannu lation and the p lacem ent of the aortic cross u se of a higher p erfu sion p ressu re d u ring CPB (66). A m an-
clam p in the patient w ith the calcified aorta. agem ent strategy for the treatment of m assive air em bolism
d u ring CPB is su m m arized in Table 26.5 (67).
Tw o d ifferent blood gas management techniques may be
■ Prevention used during CPB. Hypothermia results in an elevation of the
Alternatives in the case of the severely calcified aorta pH. Using the pH stat method, carbon dioxide is added to
inclu d e fem oral artery cannu lation, axillary artery cannu la- the CPB circuit to correct the alkalotic pH to 7.4. Using the
tion, cold fibrillatory arrest for the p lacem ent of p roxim al stat method , the numerical pH result is corrected to account
coronary artery anastom oses or for the replacem ent of a for hypothermia and no carbon d ioxid e is ad d ed . Carbon
Table 2 6 .5 M a n a gem en t of m a ssive a ir em bolu s

Table 2 6 .3 Risk fa ct or s for st rok e follow in g d u r in g ca r d iop u lm on a r y byp a ss
ca r d iop u lm on a r y byp a ss Stop the pump immediately
Preoperative Intraoperative Clamp both arterial and venous lines
Age Atherosclerosis of the ascending aorta Place the patient into deep Trendelenburg position
Peripheral vascular disease Duration of cardiopulmonary bypass Ventilate with 100% oxygen
(especially carotid artery Return to cardiopulmonary bypass Remove the aortic cannula to deair the aorta
disease) after separation
Place the arterial cannula in the SVC for retrograde cerebral perfusion,
Renal insufficiency or failure clamp the SVC proximally, and cool the patient
Diabetes mellitus Use of IABP Compress the heart manually
Previous stroke Presence of left ventricular thrombus Compress the carotid arteries manually
Urgent or emergency surgery Severe valvular calcification Once the aorta is deaired, replace the aortic cannula and resume CPB at a
Ejection fraction 40% Repeated manipulation of the aorta high pressure
Recent myocardial infarction Turn off any nitrous gas
Hypertension Consider the administration of steroids and mannitol
IABP, intra-aortic balloon pump. CPB, cardiopulmonary bypass; SVC, superior vena cava.
dioxid e ad d ed w hen using the pH stat method results in history of p ancreatitis, renal insu fficiency, and high-d ose
arteriolar dilatation in the brain. Despite increased blood calciu m ad m inistration (12,73).
flow to the brain w ith the pH stat method, cerebral autoreg-
ulation of blood flow is lost (68). The use of stat blood gas
management d uring hypothermia maintains cerebral blood
■ Prevention
flow autoregulation and improves myocard ial functional Strategies to d ecrease gastrointestinal com plications
recovery w hen compared to pH stat management (1,68). inclu d e the u se of an increased p erfu sion flow rate rather
The u se of off-p u m p coronary artery byp ass techniqu e than peripheral vasoconstrictors for m aintaining p erfusion
provid es few er m icroem boli to the brain and allow s for a p ressu re on CPB and lim itation of byp ass tim e (74). Opti-
“no tou ch” aorta technique (60). Large, rand om ized m ization of card iac ou tp u t im p roves sp lanchnic p erfu sion.
prospective trials w ill be necessary to d eterm ine w hether Manu al com p ression of the liver shou ld not be u sed to aug-
this ap p roach significantly red u ces the incid ence of neu ro- m ent venou s retu rn. The m anagem ent of gastrointestinal
logic inju ry. Treatm ent follow ing CPB and CN S inju ry com p lication focu ses on p rom p t recognition and treatm ent,
includ es neu rologic consu ltation, supp ortive care, aggres- w hich often requ ires fu rther surgery.
sive p hysical and occupational therapy, the lim itation of
cerebral ed em a w hen appropriate, and the correction of
any contribu ting m etabolic d erangem ents. ■ REFERENCES
1. Ed m u nd s LH , ed . Cardiac surgery in the adult. N ew York: McGraw -H ill;
1997.
■ GASTROINTESTINAL COMPLICATIONS 2. H am m erm eister KE, Bu rchfiel C, Johnson R, et al. Id entification of
patients at greatest risk for d eveloping m ajor com plications at card iac
The incid ence of gastrointestinal complications follow ing surgery. Circulation 1990;82(Su p p l 5):IV380–IV389.
CPB is approximately 1% (69). Gastrointestinal complica- 3. Parolari A, Alam anni F, Cannata A, et al. Off-p u m p vs. on-p u m p coro-
nary artery byp ass: m eta-analysis of currently available rand om ized
tions of CPB are often subtle and d ifficult to d etect because trials. Ann Thorac Surg 2003;76:37–40.
patients are sed ated. Diagnosis often requires transportation 4. Braunw ald E, Kloner RA. The stu nned m yocard iu m : p rolonged , p ost-
of the critically ill patient to various rad iology d epartm ents. ischem ic ventricu lar d ysfu nction. Circulation 1982;66:1146–1149.
5. Menasche P. Strategies to im p rove m yocard ial p rotection d u ring extra-
Intraoperative m onitoring of sp lanchnic perfu sion is not corp oreal circulation. Shock 2001;16(Su p p l 1):20–23.
routinely performed . Injury to the small and large bow el, 6. Jain U. Myocard ial ischem ia after card iop u lm onary byp ass. J Card Surg
gallblad d er, liver, and pancreas d uring CPB results from 1995;10(Sup pl 4):520–526.
7. Kalm an J. Arrhythm ias and p acing. In: Bu xton B, Frazier OH , Westaby
regional malperfusion second ary to hypoperfusion, vasoac- S, ed s. Ischemic heart disease surgical management. Lond on: Mosby;1999:
tive substances, cytotoxins, and microemboli. Angiotensin 87–89.
II release resu lts in sp lanchnic vasoconstriction that may be 8. Jayam VKS, Flaker GC, Jones JW. Atrial fibrillation after coronary
bypass: etiology and p harm acologic p revention. Cardiovasc Surg 2002;
harm ful in patients w ith arteriosclerosis of the splanchnic 10(4):351–358.
vessels (70,71). Red uced gastrointestinal blood flow com- 9. Brod ie JE, Johnson RB. The manual of clinical perfusion, 2nd ed . Au gu sta,
bined w ith systemic anticoagulation may cau se gastroin- GA: Glend ale Med ical Corp ; 1997.
10. N g CSH , Wan S, Yim APC, et al. Pu lm onary d ysfu nction after card iac
testinal bleed ing, gastritis, cholecystitis, ischemic small or su rgery. Chest 2002;121:1269–1277.
large bow el, hepatic d am age, and pancreatitis. Relative 11. Slad en RN , Berkow itz DE. Card iop u lm onary byp ass and the lu ng. In:
hypoperfu sion is particularly d etrim ental to the liver and Gravlee GP, Davis RF, Utley JR, ed s. Cardiopulmonary bypass principles
and practice. Baltim ore, MD: William s & Wilkins; 1993:467–487.
pancreas d u e to the lack of intrinsic autoregu lation mecha- 12. Cohn LH , Ed m u nd s LH , ed s. Cardiac surgery in the adult, 2nd ed . N ew
nism s d uring CPB (72). York: McGraw -H ill; 2003.
Ap p roxim ately 10% to 20% of p atients w ill m anifest 13. Rad y MY, Ryan T, Starr N J. Early onset of acu te p u lm onary d ysfu nc-
tion after card iovascular su rgery: risk factors and clinical ou tcom e. Crit
m ild jau nd ice second ary to blood transfu sion, hem olysis, Care Med 1997;25(11):1831–1839.
and liver inju ry (1). H ep atic inju ry can also occu r d u ring 14. H olm es JH , Connolly N C, Pau ll DL, et al. Magnitu d e of the inflam m a-
m anu al com p ression of the liver to au gm ent venou s tory response to card iopulm onary byp ass and its relation to ad verse
clinical outcom es. Inflamm Res 2002;51(12):579–586.
retu rn or to fill venou s cannu las w ith blood p rior to initia- 15. Oku bo N , H atori N , Ochi M, et al. Com p arison of m -RN A exp ression
tion of CPB. Acu te p ancreatitis occu rs in 1% of p atients, for inflam m atory m ed iators in leu kocytes betw een pu m p and off-
bu t 30% of p atients w ill have tem p orary asym p tom atic p u m p coronary artery bypass grafting. Ann Thorac Cardiovasc Surg
2003;9(1):43–49.
elevation of seru m am ylase or lip ase (12,73). Mortality is 16. Wild hirt SM, Schu lze C, Schu lz C, et al. Red u ction of system ic and car-
greatly increased w hen severe gastrointestinal com p lica- d iac ad hesion m olecu le exp ression after off-p u m p versu s conventional
tions occu r follow ing CPB, p robably the reflection of a coronary artery byp ass grafting. Shock 2001;16(Su p p l 1):55–59.
17. Sch u lze C, Con rad N , Sch u tz A, et al. Red u ced exp ression of sys-
generalized low card iac ou tp u t state. tem ic p roinflam m atory cytokines after off-p u m p versu s conven-
tional coronary artery bypass grafting. Thorac Cardiovasc Surg 2000;48(6):
364–369.
■ Risk factors 18. Wan S, LeClerc JL, Vincent JL. Inflam m atory resp onse to card iop u l-
m onary byp ass: m echanism s involved and p ossible therap eu tic strate-
Risk factors for gastrointestinal inju ry follow ing CPB gies. Chest 1997;112:676–692.
includ e ad vanced age, em ergency su rgery, prolonged 19. Kaul TK, Field s BL. Leukocyte activation d u ring card iop u lm onary
byp ass: lim itations of the inhibitory m echanism s and strategies. J Car-
d u ration of CPB, low card iac outpu t, prolonged u se of diovasc Surg (Torino) 2000;41(6):849–862.
vasopressors, p erip heral vascu lar d isease, and congestive 20. Lei Y, H aid er H K, Chu snsheng W, et al. Dose-d ep end ent effect of
heart failu re (12,70). Risks of p ancreatitis includ e previou s ap rotinin on aggravated p ro-inflam m atory cytokines in p atients w ith
p u lm onary hyp ertension follow ing card iop u lm onary byp ass. Cardio- 49. Stam ou SS, H ill PC, Dangas G. Stroke after coronary artery byp ass:
vasc Drugs Ther 2003;17(4):343–348. incid ence, p red ictors, and clinical ou tcom e. Stroke 2001;32:1508–1513.
21. Gott JP, Cooper WA, Schm id t FE, et al. Mod ifying risk for extracorpo- 50. Sotaniem i KA. Long-term neu rologic ou tcom e after card iac op eration.
real circulation: trial of fou r anti-inflam m atory strategies. Ann Thorac Ann Thorac Surg 1995;59:1336–1339.
Surg 1998;66(3):747–753. 51. John R, Choud hri AF, Weinberg AD, et al. Mu lticenter review of p reop -
22. Schm artz D, Tabard el Y, Preiser JC, et al. Does ap rotinin influence the erative risk factors for stroke after coronary artery byp ass grafting. Ann
inflam m atory response to card iopulm onary byp ass in p atients? J Tho- Thorac Surg 2000;69:30–36.
rac Cardiovasc Surg 2003;125(1):184–190. 52. Trehan N , Mishra M, Sharm a OP, et al. Fu rther red u ction in stroke after
23. Pap arella D, Yau TM, You ng E. Card iop u lm onary byp ass ind u ced off-p u m p coronary artery byp ass grafting: a 10-year exp erience. Ann
inflam m ation: pathop hysiology and treatm ent. An u p d ate. Eur J Car- Thorac Surg 2001;72(3):S1026–S1032.
diothorac Surg 2002;21:232–244. 53. McKhann GM, Grega MA, Borow icz LM, et al. Encep halop athy and
24. Weiler JM, Gellhaus MA, Carter JG, et al. A prospective study of the risk stroke after coronary artery byp ass grafting. Arch Neurol 2002;59:
of an immediate adverse reaction to protamine sulfate during cardiopul- 1422–1428.
monary bypass surgery. J Allergy Clin Immunol 1990;85(4):713–719. 54. N ew m an MF, Kirchner JL, Phillip s-Bu te B, et al. Longitu d inal assess-
25. Brooks JC. N oncard iogenic p u lm onary ed em a im m ed iately follow ing m ent of neu rocognitive function after coronary-artery byp ass surgery.
rap id protam ine ad m inistration. Ann Pharmacother 1999;33(9):927–930. N Engl J Med 2001;344(6):395–402.
26. Levy JH , Schw ieger IM, Zaid an JR, et al. Evalu ation of p atients at risk 55. Baker RA, And rew MJ, Knight JL. Evalu ation of neu rological assess-
for p rotam ine reaction. J Thorac Cardiovasc Surg 1989;98(2): 200–204. m ent and ou tcom es in card iac su rgical p atients. Semin Thorac Cardio-
27. Com u nale ME, Maslow A, Robertson LK, et al. Effect of site of venou s vasc Surg 2001;13(2):149–157.
protam ine ad m inistration, p reviou sly alleged risk factors, and p reop - 56. Mark DB, N ew m an MF. Protecting the brain in coronary artery byp ass
erative u se of asp irin on acu te p rotam ine-ind u ced p u lm onary vasocon- graft surgery. JAMA 2002;287(11):1448–1450.
striction. J Cardiothorac Vasc Anesth 2003;17(3): 309–313. 57. Ap pelblad M, Engstrom G. Fat contam ination of p ericard ial su ction
28. Hensley FA, Larach DR, Martin DE. Intraop erative anesthetic com pli- blood and its influ ence on in vitro cap illary-p ore flow p rop erties in
cations and their m anagem ent. In: Wald hau sen JA, Orringer MB, ed s. p atients u nd ergoing rou tine coronary artery byp ass grafting. J Thorac
Complications in cardiothoracic surgery. St. Lou is, MO: Mosby–Year Book; Cardiovasc Surg 2002;124(2):377–386.
1991:12–14. 58. Pae WE, William s DR, Troncelliti EK, et al. Prevention of com p lications
29. Warkentin TE, Greinacher A. H ep arin-ind u ced throm bocytop enia and d u ring card iop u lm onary byp ass. In: Wald hau sen JA, Orringer MB,
card iac su rgery. Ann Thorac Surg 2003;76:638–648. ed s. Complications in cardiothoracic surgery. St. Lou is, MO: Mosby-Year
30. Greinacher A, Levy JH . H IT hap p ens: Diagnosing and evalu ating the Book; 1991:39–44.
patient w ith hep arin-associated throm bocytop enia. Anesth Analg 59. Mills SA. Cerebral inju ry and card iac op erations. Ann Thorac Surg
2008;107(2):356–358. 1993;56(5 Su p p l):S86–S91.
31. Kerend i F, Thou rani VH , Pu skas JD, et al. Im p act of hep arin-ind uced 60. Bowles J, Lee JD, Dang CR, et al. Coronary artery bypass performed with-
throm bocytop enia on p ostop erative ou tcom es after card iac su rgery. out the use of cardiopulmonary bypass is associated with reduced cere-
Ann Thorac Surg 2007;84:1548–1555. bral microemboli and improved clinical results. Chest 2001;119:25–30.
32. Warkentin TE, Kelton JG. Tem p oral asp ects of hep arin-ind u ced throm - 61. Malheiros SM, Massaro AR, Gabbai AA, et al. Is the nu m ber of
bocytopenia. N Engl J Med 2001;344:1286–1292. m icroem boli signals related to neurologic outcom e in coronary bypass
33. Bu xton B, Frazier OH , Westaby S, ed s. Ischemic heart disease surgical su rgery? Arq Neuropsiquiatr 2001;59(1):1–5.
management. Lond on: Mosby; 1999. 62. Lee JD, Lee SJ, Tsu shim a WT, et al. Benefits of off-p u m p byp ass on neu -
34. Ranucci M. Antithrom bin III. A key factor in extracorp oreal circulation. rologic and clinical m orbid ity: a p rosp ective rand om ized trial. Ann
Minerva Anestesiol 2002;68(5):454–457. Thorac Surg 2003;76(1):18–25.
35. Barrons RW, Jahr JS. A review of p ost-card iop u lm onary byp ass bleed - 63. Borger MA, Feind el CM. Cerebral em boli d u ring card iop u lm onary
ing, am inocaproic acid , tranexam ic acid , and ap rotinin. Am J Ther bypass: effect of perfusionist interventions and aortic cannu las. J Extra
1996;3(12):821–838. Corpor Technol 2002;34(1):29–33.
36. Weerasinghe A, Taylor KM. The p latelet in card iop u lm onary byp ass. 64. Likosky DS, Leavitt BJ, Marin CAS, et al. Intra- and p ostop erative p re-
Ann Thorac Surg 1998;66:2145–2152. d ictors of stroke after coronary artery byp ass grafting. Ann Thorac Surg
37. Wood m an RC, H arker LA. Bleed ing com p lications associated w ith car- 2003;76:428–435.
d iop ulm onary byp ass. Blood 1990;76(9):1680–1697. 65. Tu m an KJ, McCarthy RJ, Rajafi H , et al. Differential effects of ad vanced
38. Habib RH , Zacharias A, Schw ann TA, et al. Ad verse effects of low age on neu rologic and card iac risks of coronary artery op erations. J
hem atocrit d u ring card iop ulm onary byp ass in the ad ult: shou ld current Thorac Cardiovasc Surg 1992;104(6):1510–1517.
practice be changed ? J Thorac Cardiovasc Surg 2003;125(6):1438–1450. 66. Gold JP, Charlson ME, William s-Ru sso P, et al. Im p rovem ent of ou t-
39. Horrow JC. Managem ent of coagulop athy associated w ith card iopul- com es after coronary artery byp ass. A rand om ized trial com p aring
monary bypass. In: Gravlee GP, Davis RF, Utley JR, ed s. Cardiopul- intraop erative high versu s low m ean arterial p ressu re. J Thorac Cardio-
monary bypass principles and practice. Baltim ore, MD: William s & Wilkins; vasc Surg 1995;110(5):1302–1311.
1993:436–466. 67. Mills N L, Morris JM. Air em bolism associated w ith card iop u lm onary
40. Klem perer JD. Thyroid horm one and card iac su rgery. Thyroid 2002;12 bypass. In: Wald hau sen JA, Orringer MB, ed s. Complications in cardio-
(6):517–521. thoracic surgery. St. Louis, MO: Mosby-Year Book; 1991:60–67.
41. Kenned y DT, Bu tterw orth JF. End ocrine fu nction d u ring and after car- 68. Rogers AT, N ew m an SP, Stu m p DA, et al. N eu rologic effects of car-
d iop ulm onary byp ass: recent observations. J Clin Endocrinol Metab d iop u lm onary byp ass. In: Gravlee GP, Davis RF, Utley JR, ed s. Car-
1994;78(5):997–1002. diopulmonary bypass principles and practice. Baltim ore, MD: William s &
42. Utley JR. Renal function and flu id balance w ith card iop ulm onary Wilkins; 1993:542–576.
bypass. In: Gravlee GP, Davis RF, Utley JR, ed s. Cardiopulmonary bypass 69. H alm MA. Acu te gastrointestinal com p lications after card iac su rgery.
principles and practice. Baltim ore, MD: William s & Wilkins; 1993:488–508. Am J Crit Care 1996;5(2):109–118.
43. Conlon PJ, Stafford -Sm ith M, White WD, et al. Acu te renal failure fol- 70. Zacharias A, Schw ann TA, Parenteau GL, et al. Pred ictors of gastroin-
low ing card iac surgery. Nephrol Dial Transplant 1999;14:1158–1162. testinal com p lications in card iac su rgery. Tex Heart Inst J 2000;27:
44. Rind er CS, Fontes M, Matthew JP, et al. N eu trop hil CD11b u p regu la- 93–99.
tion d u ring card iop u lm onary byp ass is associated w ith p ostop erative 71. Reilly PM, Bu lkley GB. Vasoactive m ed iators and sp lanchnic p erfu -
renal injury. Ann Thorac Surg 2003;75(3):899–905. sion. Crit Care Med 1993;21(Su p p l 2):S55–S68.
45. Su en WS, Mok CK, Chiu SW, et al. Risk factors for d evelop m ent of 72. Shangraw RE. Metabolic and sp lanchnic visceral effects of card iopu l-
acute renal failure (ARF) requ iring d ialysis in p atients u nd ergoing car- m onary bypass. In: Gravke GP, Davis RF, Utley JR, ed s. Cardiopulmonary
d iac surgery. Angiology 1998;49(10):789–800. bypass principles and practice. Baltimore, MD: William s & Wilkins; 1993:
46. Ranucci M, Pavesi M, Mazza E, et al. Risk factors for renal d ysfu nction 509–541.
after coronary surgery: the role of card iopulm onary bypass technique. 73. Fernand ez-d el Castillo C, H arringer W, Warshaw AL, et al. Risk factors
Perfusion 1994;9(5):319–326. for p ancreatic cellu lar inju ry after card iop u lm onary byp ass. N Engl J
47. Bold t J, Brenner T, Lehm ann A. Is kid ney fu nction altered by the d u ra- Med 1991;325(6):382–387.
tion of card iop u lm onary byp ass? Ann Thorac Surg 2003;73(3):906–912. 74. Plestis KA, Gold JP. Im p ortance of blood p ressu re regu lation in m ain-
48. Taggart DP, Westaby S. N eu rological and cognitive d isord ers after taining ad equate tissu e perfu sion d uring card iop ulm onary bypass.
coronary artery byp ass grafting. Curr Opin Cardiol 2001;16:271–276. Semin Thorac Cardiovasc Surg 2001;13(2): 170–175.
CHAPTER
27
Complications of Surgical
Coronary Revascularization
Spencer J . Melby, Traves D. Crabtree, and Marc R. Moon
■ INTRODUCTION ■ OVERALL MORBIDITY AND MORTALITY

Despite ad vances in p ercutaneou s techniqu es for coronary With regard to monitored outcome variables, coronary
revascu larization, coronary artery bypass surgery rem ains revascularization is one of the most scrutinized surgical pro-
an integral com p onent of the treatm ent regim en for ced ures performed . With the d evelopm ent of the Society of
p atients w ith coronary artery d isease. Critical analysis of Thoracic Surgeons (STS) database, surveillance of periopera-
clinical ou tcom es w ith su bsequ ent im p rovem ents in care, tive morbidity and mortality and identification of significant
inclu d ing critical care m anagem ent and m yocard ial p rotec- comorbid cond itions have allow ed for an unpreced ented
tion techniqu es, have significantly im proved ou tcom es mod el of quality control on a local, regional, and national
related to su rgical revascu larization. Based on previou s basis. The STS d atabase has also permitted the d evelopment
comp arisons w ith nonsurgical techniqu es, current gu id e- of risk stratification mod els that can estimate perioperative
lines for coronary artery byp ass grafting (CABG) inclu d e mortality and morbid ity based on multiple potential risk
left m ain coronary artery stenosis, triple-vessel d isease, factors and comorbid cond itions. A report from the STS
single- or d ou ble-vessel d isease that includ es left anterior d atabase of 595,222 isolated coronary revascularization pro-
d escend ing stenosis in p atients w ith p oor left ventricu lar ced ures performed betw een 2000 and 2003 d emonstrated an
(LV) fu n ction, an d d isease refractory to n onsu rgical overall 30-day operative mortality of 2.54% (11). Risk factors
m anagem ent (1). CABG has better long-term ou tcomes, for perioperative d eath includ ed increasing age, renal d ys-
esp ecially in p atients w ith d iabetes or other high risk function, emergency surgery, card iogenic shock, and repeat
comorbid ities (2,3). operations. Perioperative mortality is closely linked to post-
Continu ed efforts to d ecrease m orbid ity and m ortal- operative morbidity, and many of the risk factors identified
ity associated w ith su rgical revascu larization have for mortality correlate w ith the d evelopm ent of surgery-
resu lted in p ersisten t su rvival ad vantage and d ecreased related complications (12).
need for rein terven tions relative to nonsu rgical revascu - One area of stu d y that has received attention recently is
larization techniqu es. Based u p on rand om ized controlled m aintenance of norm oglycem ia. Control of hyp erglycem ia
trials of p atien ts w ith stable angin a, CABG h as been has been d em onstrated in m u ltip le stu d ies to d ecrease the
show n to p rovid e a significant su rvival ad vantage in rates of m ortality and m orbid ity, esp ecially in w ou nd infec-
m od erate to high -risk p atients at 5, 7, and 9 years follow - tions and occu rrences of stroke (13–15). The STS set out
u p com p ared to m ed ical m an agem ent (4–8). A m eta- p ractice gu id elines concerning blood glu cose m anagem ent
analysis of rand om ized trials also d em onstrated a d u ring ad u lt card iac su rgery (16). Key p oints inclu d ed evi-
significant long-term su rvival ad vantage of CABG over d ence that p oor p eriop erative glycem ic control is associ-
p ercu taneou s translu m inal coronary angiop lasty (PTCA) ated w ith increased m orbid ity and m ortality, and that
and a su bstantial d ecrease in the nu m ber of rep eat inter- control of blood sugar with a standardized insulin regimen
ventions requ ired follow in g CABG relative to PTCA (9). should be utilized to maintain blood glucose levels 180 mg/
These d ifferences w ere m ost notable in p atients w ith d L in p atients w ith d iabetes. Glycem ic control is u nneces-
m u ltivessel d isease or d iabetes. The p u rp orted ben efits sary in nond iabetic p atients provid ed that glu cose levels
of d ru g-elu tin g d evices have not been realized in th e rem ain 180 m g/ d L (16). Evid ence also exists to show that
short or m id term (10). Long-term investigations com p ar- excessively tight control of glu cose levels m ay increase
ing contem p orary coronary stent technology to CABG m orbid ity and m ortality (17).
are cu rrently u navailable bu t m ay have an im p act on Table 27.1 su m m arizes the incid ence of several m ajor
clinical p ractice in th e fu tu re. comp lications associated w ith CABG based on a review of
the STS d atabase (11). The characteristics of the p opulation
u nd ergoing coronary revascularization have changed con-
sid erably over the p ast d ecad e, increasing the com plexity
Spencer J. Melby, Traves D. Crabtree, Marc R. Moon: of the su rgery as w ell as p ostop erative care. Review of the
Washington University School of Med icine, St. Louis, MO 63110. STS d atabase d em onstrates that from 1990 to 1999, patients
298
Chapter 27 • Complications of Surgical Coronary Revascularization 299
Table 2 7 .1 In cid en ce of m a jor com p lica t ion s Preop erative id entification of risk factors allow s for risk
follow in g isola t ed cor on a r y stratification and p atient ed u cation bu t m ay also help to
r eva scu la r iza t ion (STS D a t a ba se, p lan the op eration in ord er to d ecrease the rate of stroke.
1997–2000) Patients w ith sym ptom atic carotid artery stenosis or criti-
cal asym p tom atic stenosis d iagnosed p reop eratively m ay
Complication Incidence (%) u nd ergo end arterectom y prior to bypass surgery or at the
30-day mortality 2.54 time of the byp ass op eration. Preop erative carotid d uplex
scanning is p erform ed in p atients w ith a history of a tran-
Permanent stroke 1.50
sient ischem ic attack (TIA), stroke, am au rosis fugax, or in
Renal failure requiring dialysis 3.53 p atients w ith a carotid bru it. Patients w ith 80% stenosis,
Prolonged mechanical ventilation ( 48 hr) 7.24 corresp ond ing to an internal carotid artery to com m on
Deep sternal wound infection 0.50 carotid artery (IC:CC) velocity ratio 4.0, typically
u nd ergo CABG alone. For p atients w ith high-grad e carotid
Reoperation for bleeding 6.19
stenosis (IC:CC velocity ratio 4.0) carotid end arterectom y
Any major morbidity/mortality 13.83 is necessary before card iop u lm onary byp ass to m inim ize
the risk of stroke. The ap p roach d iffers d ep end ing on the
From DiSesa VJ, O’Brien SM, Welke KF, et al. Contemporary impact of state
certificate-of-need regulations for cardiac surgery: an analysis using the Society of d egree of card iac d isease. Tim ing of end arterectom y for
Thoracic Surgeons’ National Cardiac Surgery Database. Circulation 2006;114(20): p atients w ith significant bu t asym p tom atic carotid stenosis
2122–2129. remains a su bject of d ebate. For p atients w ith u nstable
angina and p reserved LV fu nction, sim u ltaneou s carotid
end arterectom y and CABG are p erform ed . For patients
have becom e significantly old er and are m ore likely to have w ith stable angina and severe LV d ysfu nction, carotid
a history of sm oking, d iabetes, renal failure, hyp ertension, end arterectom y is p erform ed 1 to 2 d ays p rior to coronary
stroke, chronic lu ng d isease, w orsening heart failu re, and revascu larization. Patients w ho u nd ergo com bined CABG
mu ltivessel d isease. Risk stratification m od els have also and carotid end arterectom y often have significant hem o-
show n that p red icted operative risk has risen from 2.6% in d ynam ic flu ctu ation in the im m ed iate p ostop erative p eriod
1990 to 3.4% in 1999 w hile the observed operative m ortality d u e to carotid bod y m anip u lation. Althou gh these flu ctua-
has d ecreased from 3.9% to 3.0% (18). Althou gh ad vances tions d o not affect p atients w ith norm al LV fu nction, the
in su rgical and periop erative care have resu lted in im prove- occu rrence m akes p atients w ith p oor LV fu nction d ifficu lt
ment in clinical ou tcom es, the increasing com p lexity of the to manage p erioperatively.
patients w ill requ ire continu ing efforts to und erstand and The application of transesophageal echocardiography
im prove ou tcom es related to CABG. and sensitive epiaortic echocardiography has improved the
ability to diagnose and characterize a severely atheroscle-
rotic aorta (28). This diagnosis poses a formidable challenge
■ NEUROLOGIC COMPLICATIONS to the surgeon. The advancement of “no-touch” techniques
One of the m ost d evastating com plications follow ing coro- that avoid manipulation or clamping of the d iseased ascend-
nary revascu larization is the d evelopm ent of stroke. The ing aorta may be used w ith or w ithout card iopulmonary
rep orted incid ence of stroke follow ing CABG is 1.1% to bypass (29,30). Application of such techniques has been
2.9% w ith an associated in-hospital m ortality of 22% to show n to significantly decrease the incidence of stroke in
24.8% and a 5-year m ortality of 56% (18–22). Risk factors high-risk patients und ergoing coronary revascu larization
for the d evelopm ent of stroke by m u ltivariate analysis (30). Another op tion for p atients w ith a severely atheroscle-
inclu d e the p resence of a calcified aorta, prior stroke, rotic aorta involves institu tion of circulatory arrest and
increasing age, carotid artery d isease, increasing d u ration replacem ent of the ascend ing aorta to lim it the incid ence of
of card iop u lm onary bypass, u nstable angina, renal failu re, stroke in this p op u lation (31). Recently d eveloped intra-
perip heral vascu lar d isease, sm oking history, and d iabetes aortic filters m ay be u sed in conju nction w ith the aortic
mellitu s (18,19,22,23). The m ost significant risk factor cannu la to d ecrease the em bolic load d u ring card iop u l-
am ong these is the presence of an atherosclerotic ascend ing m onary byp ass and m ay p lay a fu tu re role in red u cing the
aorta, w ith atheroem boli accounting for the m ajority of rate of stroke (32,33).
severe ischem ic strokes. The presence of m obile p laqu es in Off-p u m p CABG (OPCAB) has been fou nd to be p ro-
the ascend ing aorta has been associated w ith a stroke rate tective against strokes in several series, inclu d ing a large
as high as 33.3% follow ing coronary bypass surgery (24,25). retrosp ective stu d y of p atients in the N ew York State Reg-
Manip u lation of the aorta w ith or w ithou t the institu tion of istry; the ad ju sted od d s ratio for OPCAB versu s on-p u m p
card iopu lm onary bypass is a significant risk factor for w as 0.70 (95% confid ence interval 0.57 to 0.86) (34). In a
stroke follow ing coronary revascu larization (26). Em boli retrosp ective review of 42,477 consecu tive, nonem ergency,
accou nt for 80% of strokes after card iac su rgery w ith isolated CABG cases in the STS d atabase (over 16,000
w atershed infarcts contribu ting to the other sou rces of p atients u nd erw ent OPCAB versu s over 26,000 p atients
ischem ic events (27). w ho u nd erw ent conventional on-p u m p CABG), the stroke
300 Part IIII • Complications of Thoracic Surgery
rate d ecreased in p atient w ho u nd erw ent OPCAB (od d s onset of atrial fibrillation. Acu te hyp otension or a low car-
ratio w as 0.65, 95% confid ence interval 0.52–0.80, p 0.001) d iac ou tp u t state accou nt for m ost sym p tom s and are often
(35). related to a rap id ventricu lar resp onse to the atrial rhythm .
Areas of controversy w ith regard to the cond u ct of the In these circu m stances, u rgent treatment to control the ven-
op eration and its effect u p on neu rologic ou tcom e inclu d e tricu lar rate is requ ired . In ad d ition to acu te sym p tom s, the
the u se of a single or sequential clam p technique, tem p era- d evelop m ent of p ostop erative atrial fibrillation signifi-
tu re m anagem ent strategies d uring and after bypass, and cantly increases the risk of stroke follow ing coronary revas-
periop erative m anagem ent of hyperglycem ia. cu larization (46,47). The loss of norm al atrial contraction
Unfortu nately, there are few treatm ent options for resu lts in the d evelop m ent of throm bu s w ithin the atriu m
patients w ho d evelop an intraoperative or periop erative that serves as a sou rce for em boli. Su ch throm bus m ay
stroke. A small nu m ber of patients w ith a throm boem bolic d evelop w ithin 48 hou rs from the onset of fibrillation. The
etiology m ay benefit from early ( 6 to 8 hours after the m orbid ity associated w ith p ostop erative atrial fibrillation
event) throm bolytic therapy. resu lts in p rolonged hosp ital stay, p rolonged intensive care
Neurocognitive changes or encephalopathy may occur u nit (ICU) stay, increased hosp ital costs, and need for hos-
follow ing bypass surgery. Encephalopathy is present in 3.0% p ital read m ission after d ischarge (41,43,46–48).
to 6.9% of patients und ergoing CABG and is associated w ith Many trials have exam ined the p revention of p ostop er-
an increased length of stay and mortality relative to patients ative atrial fibrillation by p eriop erative p harm acotherap y.
w ithout encephalopathy (21,36). Significant risk factors for Prop hylactic ad m inistration of -blockers has consistently
postoperative encephalopathy or neurocognitive changes been show n to d ecrease p ostop erative atrial fibrillation
include increasing age, the presence of a carotid bruit, hyperin rand om ized controlled trials, esp ecially in p atients w ho
tension, diabetes mellitus, pulmonary disease, excessive alco- received p reop erative -blockad e. Other trials have
hol consumption, and history of a previous stroke (21,36). d em onstrated that p reop erative ad m inistration of am io-
More stringent neuropsychometric tests have estimated that d arone d ecreases the rate of p ostop erative atrial fibrillation
19% to 26% of patients have persistent cognitive d eficits for after byp ass su rgery (49,50). Criticism s of am iod arone pro-
2 months follow ing coronary revascularization surgery p hylaxis have inclu d ed an inability to rep rod u ce these
(37). The etiology of these subtle deficits is incompletely resu lts in su bsequ ent trials u sing sim ilar regim ens of am io-
understood, although microembolization may play a role. d arone and failu re of trials to d em onstrate a benefit over -
Although the use of cardiopulmonary bypass has been blockers (51,52). A recent meta-analysis of randomized trials
implicated, studies have failed to identify long-term differ- suggests that preoperative ad m inistration of -blockers,
ences in neurocognitive testing 3 to 12 months post bypass sotalol, and am iod arone are all effective at p reventing post-
betw een patients undergoing on-pump revascularization op erative atrial fibrillation in card iac p atients (53). Despite
versus off-pum p revascularization (38–40). the ability of these agents to d ecrease the rate of p ostop era-
tive atrial fibrillation, their p rop hylactic ad m inistration has
not resulted in a significant d ecrease in the length of stay or
■ POSTOPERATIVE ARRHYTHMIAS in overall hosp ital costs (51,53–55).
Postop erative arrhythmias are a com mon problem follow - A practical limitation of preoperative prophylaxis w ith
ing coronary bypass su rgery, w ith atrial fibrillation accou nt- -blockers or amiod arone in patients requiring coronary
ing for the m ajority of occurrences. The incid ence of revascu larization is the inability to p rovid e an ad equ ate
postoperative atrial fibrillation follow ing coronary revascu - therapeutic regimen prior to surgery. In most patients, cur-
larization is 23% to 40%, w ith even higher rates reported rent surgical practice involves CABG w ithin 1 to 2 days of
among patients u nd ergoing combined bypass and valve catheterization, making preoperative treatment impractical.
surgery (41–46). The pathophysiology of atrial fibrillation is Recent randomized trials have demonstrated that immediate
related to the d evelopment of reentrant circuits w ithin the postoperative administration of metoprolol or amiodarone
atriu m or p ulmonary veins. Potential risk factors for atrial significantly d ecreases the incid ence of p ostop erative atrial
fibrillation inclu d e ad vanced age, male gend er, chronic fibrillation (54,56). Prop h ylactic ad m in istration of oth er
obstructive pulmonary d isease (COPD), left atrial enlarge- agents such as digoxin, calcium channel blockers, and mag-
ment, a preoperative history of paroxysmal atrial fibrillation, nesium sulfate have shown mixed results (47,57–63).
increasing severity of coronary artery disease, and preopera- A novel techniqu e for the p revention of p ostop erative
tive d igoxin use (42,45,46). Among these, ad vanced age is atrial fibrillation involves biatrial overd rive p acing in the
the most consistent pred ictor of postoperative atrial fibrilla- early p ostop erative p eriod . Pacing w ires are p laced in both
tion. Follow ing coronary revascularization, the incid ence of atria intraop eratively and the p atient u nd ergoes overd rive
atrial fibrillation is 26% in patients younger than 70 and 45% p acing for 4 to 5 d ays p ostop eratively. Rand om ized stud ies
in patients older than 70 (41). have d emonstrated a significant red uction in postoperative
Atrial fibrillation typ ically d evelops betw een postoper- atrial fibrillation w ith biatrial p acing (64–67). Althou gh this
ative d ays 1 and 5 and is often asym p tom atic. Som e techniqu e d ecreases the incid ence of atrial fibrillation,
patients d evelop hypotension or exp erience shortness of these stu d ies have not d em onstrated a consistent d ecrease
breath, chest p ain, palp itations, or confu sion w ith acu te in hosp ital length of stay (64–67).
Initial treatm ent of atrial fibrillation is based on the Many p atients w ill convert to sinu s rhythm im m ed i-
severity of sym p tom s. Im m ed iate electrical card ioversion ately after initiation of treatm ent. Patients w ho d o not con-
is ind icated in the p resence of hem od ynam ic instability, vert w ithin the first 24 to 48 hou rs are at risk for m ural
w orsening LV d ysfu nction, or ischem ia. Am ong p atients throm bu s w ithin the atrium that may serve as a source of
w ho are relatively asym ptom atic, initial m anagem ent em boli. Patients w ho rem ain in atrial fibrillation for 24
strategies inclu d e id entification and treatm ent of u nd erly- hou rs m ay be started on a low -d ose hep arin d rip at 500 to
ing abnorm alities su ch as hypoxia, hypovolem ia or hyp er- 800 u nits p er hou r. Anticoagu lation w ith hep arin follow ed
volem ia, hyp okalem ia, hypom agnesem ia, and elim ination by Coum ad in has been show n to d ecrease the risk of
of chronotrop ic d rugs. Agents u sed for rate control inclu d e throm boem bolic events in patients w ith persistent postop-
m etop rolol and d iltiazem , w hich can be given intra- erative atrial fibrillation (75,76). In the absence of anticoag-
venou sly initially and subsequ ently as an oral m aintenance u lation, attem p ts at p harm acologic card ioversion w ith
d ose. Althou gh u sed less frequ ently, d igoxin can be given agents su ch as am iod arone or electrical card ioversion have
w hen other agents are contraind icated . These agents are been associated w ith a 1% to 7% risk of throm boem bolism
titrated to a resting ventricu lar heart rate of 80 to 110 beats (77,78). Patients w ith p ersistent or recu rrent atrial fibrilla-
per m inu te, p rovid ed that there is an absence of sym p tom s tion are m aintained on Cou m ad in for 4 to 6 w eeks postop-
or hem od ynam ic com p rom ise. eratively to m inim ize the risk of throm boem bolic events.
Rate control w ith -blockers or calciu m channel block-
ers m ay also resu lt in conversion to sinu s rhythm . Other
antiarrhythm ic agents m ay also be given sp ecifically to
■ STERNAL WOUND COMPLICATIONS
convert p atients to sinu s rhythm . Ad m inistration of intra- Accord ing to the STS d atabase, the incid ence of sternal
venou s am iod arone has been show n to restore sinu s w ou nd infections in 2006 w as 0.3% am ong isolated coro-
rhythm w ithin 24 hou rs in 77% to 83% of card iac su rgical nary artery byp ass p roced u res (79). A p revious su rveil-
p atients (68–70). Other agents su ch as p rop afenone and lance of over 2,400 p atients d em onstrated an overall chest
sotalol have not been as effective as am iod arone for con- infection rate of 3% am ong coronary artery bypass patients,
version to sinu s rhythm (71,72). Sid e effects of long-term w ith 1.6% su p erficial infections and 1.4% d eep sternal
am iod arone ad m inistration inclu d e p u lm onary fibrosis, w ou nd infections (80,81). It is exp ected that this rate w ill
hepatic toxicity, and hyp othyroid ism , althou gh these sid e increase d u e to a trend tow ard increasing com orbid ities
effects occu r infrequ ently w ith short-term ( 6 w eeks) treat- and d ecreasing LV fu nction am ong p atients u nd ergoing
ment (73). byp ass su rgery. The m ost comm on organism s isolated
Table 27.2 ou tlines an approach to the m anagem ent of from sternal w ou nd infections are stap hylococcal sp ecies.
postop erative atrial fibrillation. In patients w ho are hem o- The average tim e from operation to d iagnosis of sternal
d ynam ically stable, am iod arone 150 m g is ad m inistered w ou nd infection is 15 to 19 d ays, w ith m ost d iagnosed after
intravenou sly, follow ed by initiation of oral am iod arone, d ischarge (82).
400 m g three tim es a d ay. If the patient has a controlled Risk factors for the d evelop ment of sternal w ound
heart rate at the onset of atrial fibrillation ( 100 beats p er infections inclu d e steroid u se, d iabetes m ellitu s, reopera-
m inu te), the intravenou s load ing d ose can be elim inated . If tion for bleed ing, increasing op erative d u ration, heart fail-
the heart rate rem ains 120 beats per m inu te, intravenou s u re, increased nu m ber of grafts p erform ed , and prolonged
am iod arone bolu s is repeated or m etoprolol or d iltiazem is m echanical ventilation (80,83). Previou s rep orts have id en-
ad ministered for rate control. A d iltiazem d rip m ay also be tified the u se of bilateral internal m am m ary arteries as a
u sed for rate control in this setting. Fortu nately, am ong significant risk factor for the d evelop m ent of d eep sternal
patients w ithou t a preoperative history of atrial arrhyth- w ou nd infections (84,85). Most recent stud ies have d emon-
m ias, over 98% w ill retu rn to sinus rhythm w ithin 8 w eeks strated a sim ilar infection rate w ith u se of bilateral internal
after card iac su rgery (74). mammary arteries versus use of a single internal mammary
Table 2 7 .2 Tr ea t m en t op t ion s for a cu t e m a n a gem en t of p ost op er a t ive

a t r ia l fi br illa t ion
Drug Initial IV Dose Maintenance Dose
Amiodarone 150 mg bolus 0.5 mg/min drip 400 mg p.o. t.i.d. 5 days (load) followed by
200–400 mg p.o. q.d. for 4–6 weeks
Metoprolol 2.5–5 mg bolus q 5–10 min (max. 3 doses) 12.5–100 mg p.o. b.i.d.
Atenolol 5–10 mg q 5–10 min 25–100 mg p.o. q.d. or b.i.d.a
Diltiazem 2.5–5 mg bolus q 10 min initiation of 30–90 mg p.o. q.i.d.
IVdrip at 5–15 mg/hr
a
Extended release form may be dosed once daily.
artery in nond iabetics (86,87). A pu rported ad vantage of ■ POSTOPERATIVE MYOCARDIAL ISCHEMIA

use of both internal m am m ary arteries is a d ecrease in
recu rrent angina p ost-CABG and a d ecrease in overall car- Although uncom m on after coronary revascu larization,
d iac m orbid ity (86,87). Skeletonization of the internal m yocard ial ischem ia or infarction (MI) can occu r and is fre-
mam m ary artery d uring mobilization rather than creation qu ently d ifficu lt to d iagnose in the early p ostop erative
of a large p ed icle m ay d ecrease the rate of sternal w ou nd p eriod . Postop erative MI is estim ated to occu r in 1% to 2%
infections (88). Use of bilateral internal m am mary arteries of p atients u nd ergoing CABG (93). Risk factors for postop-
w ith or w ithou t skeletonization m ay still increase the risk erative ischem ia inclu d e the p resence of p reop erative
of sternal w ou nd com p lications in high-risk p atients su ch u nstable angina and increasing byp ass tim e, w ith a bypass
as obese d iabetic w om en, patients w ith COPD, and in tim e of 100 m inu tes associated w ith a MI rate of 7.7%
patients u nd ergoing a repeat sternotom y (89,90). (93). Off-pu mp coronary revascu larization m ay be associ-
Becau se d iabetes is a significant risk factor for sternal ated w ith a hyp ercoagulable state in the early postoperative
w ou nd infections and becau se hyp erglycem ia has a d eter- p eriod requ iring aggressive antip latelet therapy (94,95).
mined effect u p on w ound healing, investigations of the Complicated revascularizations, such as those requiring
im pact of im proved glu cose control perioperatively have coronary end arterectomy or grafting of small d iffusely d is-
been p erform ed . Continu ou s periop erative intravenou s eased vessels, may also require aggressive antiplatelet ther-
infusion of insu lin d ecreased the rate of d eep sternal ap y to avoid early graft failu re.
w ound infections to 0.8% from 2.0% am ong patients receiv- The d iagnosis of m yocard ial ischem ia in the early p ost-
ing stand ard subcutaneou s insulin injections (p 0.01) op erative p eriod can be challenging. The p resence of Q
(91). Continu ou s infu sion of insulin has been show n to w aves is not associated w ith significant m yocard ial tissue
d ecrease overall hosp ital mortality am ong d iabetics und er- d am age and is not p red ictive of early m ortality follow ing
going CABG relative to controls (2.5% vs. 5.3%, p 0.0001) coronary revascu larization (96). Prosp ective stu d ies have
(15). One p rotocol for insulin infusion consists of three reg- d em onstrated that conventional biochem ical m arkers for
im ens⎯a conservative regim en, a m od erate regim en, and p ostop erative infarction, su ch as CK-MB, trop onin T, and
an aggressive regim en. The choice of regim en is based on trop onin I, are u nreliable in d eterm ining graft occlu sion
the p atient’s p reop erative insu lin d ose or oral hyp o- p ost bypass because there is significant overlap in these
glycem ic agent, recent hem oglobin A1-C level, and most values am ong patients w ith and w ithou t graft occlu sion
recent p reop erative blood glucose level. Depend ing on the (97). If p ostop erative infarction or severe ischem ia is id enti-
regim en and the blood glucose level, w hich is m onitored fied , efforts shou ld be m ad e to evalu ate graft fu nction w ith
every 1 to 2 hou rs, insu lin infu sion m ay range betw een reexploration or u rgent catheterization to id entify and cor-
0.5 u nits p er hou r and 10 u nits p er hour. rect the cau se of ischem ia.
Signs and sym p tom s of chest w ou nd infections inclu d e Recent evid ence su pports the u se of statin therapy in
purulent d rainage, erythem a, sternal instability, fever, and p atients u nd ergoing card iac su rgery. Althou gh no rand om -
pain. Clinical history and physical examination are fre- ized controlled stu d ies have been p erform ed , retrosp ective
qu ently d iagnostic, althou gh a com pu ted tom ography (CT) review s have show n that patients receiving lipid -low ering
scan m ay help d elineate the d eep extent of the infectiou s statin m ed ications have d ecreased ad verse card iac events,
process. Wou nd cu ltu res should be p erform ed to d irect inclu d ing all-cau se m ortality and stroke in the p ostop era-
antibiotic therap y. Su rgical d ebrid em ent is invariably nective p eriod (98–101). Cessation of statin therap y p ostop era-
essary. Care m u st be taken to d ebrid e all necrotic sternal tively has been show n to increase in-hospital m ortality in
tissu e or bone and avoid inju ry to u nd erlying stru ctu res, p atients w ho u nd erw ent CABG (100). Stu d ies w hich have
such as the thin-w alled right ventricle, w hich can be ad her- separated p atients into hyp erlipid em ic and norm olipi-
ent to the p osterior sternum . H istorical m anagem ent strate- d em ic grou p s have fou nd that the p rotective benefit is only
gies for d eep sternal w ou nd infections includ ed sternal fou nd in p atients that are hyp erlip id em ic; therefore u se of
w ou nd d ebrid em ent follow ed by sternal rew iring u sing a statin therap y shou ld be targeted to that grou p (98). Periop-
closed d rainage system . H ow ever, early coverage of the erative statin therap y shou ld be given to any hyp erlip i-
w ou nd w ith p ectoralis m yocu taneou s ad vancem ent flap s d em ic p atient p lanning to u nd ergo CABG and shou ld not
and greater om ental transposition into the w ound have be d iscontinu ed in the postoperative period in any patient
been associated w ith a d ecreased length of stay, m ortality, that is receiving the m ed ication.
and recu rrent infection rate versus the stand ard ap p roach
(92). Coverage of the w ou nd can be perform ed after ad e- ■ COMPLICATIONS OF CONDUIT
qu ate d ebrid em ent of all necrotic or infected tissue, usu ally
HARVEST SITES
w ithin 3 to 5 d ays. Most patients can be extu bated shortly
after sternal d ebrid em ent. After 3 to 5 d ays of d ressing One of the m ost frequ ent sou rces of com p laints follow ing
changes, d efinitive closure of the w ound is perform ed . byp ass su rgery is related to th e sap h enou s vein h arvest
Patients w ho p resent late or have significant sepsis can site. The incid ence of leg w ou nd com p lications follow ing
expect a prolonged ICU and hosp ital stay and an increased sap henou s vein harvesting is 1% to 28%, w ith variability
mortality rate. related to d ifferen ces in the d efinition of leg w ou n d
complications as w ell as variations in harvesting techniques d em onstration of ad equ ate collateral blood su p p ly from
(80,82,102–105). Common minor complications inclu d e d er- the u lnar d istribu tion u sing an Allen test is ad equ ate for
matitis, cellulitis, greater saphenous nerve paresthesias, p reventing significant ischem ic inju ry w ith rad ial artery
persistent leg sw elling, serom as, and lymphoceles. Major harvesting. Carefu l su rgical techniqu e w ith avoid ance of
leg w ound com plications requiring ad d itional su rgical pro- inju ry or traction on the su perficial rad ial nerve may help
ced u res occur in less than 0.7% of patients, w ith nonhealing limit the d egree of neu rologic inju ry associated w ith rad ial
w ound s and w ound necrosis accounting for the majority artery harvesting. N ew er techniqu es of end oscopic rad ial
(102,106). Risk factors for the d evelopment of major leg artery harvesting are cu rrently u nd er investigation (119).
w ound complications includ e female gend er, peripheral Good resu lts have been obtained , bu t risk of neurologic
vascular d isease, and use of an intra-aortic balloon pump com p lications m u st be w eighed against im p roved cosm etic
(102). These risk factors emphasize the contribution of vas- resu lts com p ared to the op en techniqu e (120–122).
culopathy and peripheral ischemia to the d evelopment of
complications.
Several techniqu es are u sed to harvest the sap henou s
■ COMPLICATIONS RELATED TO HEMOSTASIS
vein, inclu d ing a single incision extend ing over the entire Postoperative bleed ing is a significant early com plication
length of the vein, several sm aller interm ittent incisions follow ing CABG. The incid ence of reexp loration for bleed -
w ith skin brid ges, and end oscopic techniqu es that fu rther ing is 2% to 4% for isolated coronary revascu larization and
lim it the extent of incisions. End oscopic techniqu es have accou nts for the m ajority of p atients requ iring reoperation
recently been d evelop ed to d ecrease w ou nd com p lications (79,123,124). The m ost com m on etiology of bleed ing at the
associated w ith stand ard open techniqu es. Prosp ective tim e of reop eration is a su rgical cau se (67%); d iffu se bleed -
stu d ies have p rovid ed varying resu lts regard ing the ability ing related to coagu lop athy accou nts for the remaining
of end oscop ic vein harvest techniqu es to d ecrease the local third (123). Reop eration for bleed ing is associated w ith an
w ou nd com p lication rate com p ared to stand ard op en tech- inhosp ital mortality three tim es higher than for p atients
niqu es (105,107,108). The learning cu rve, the cost of ad d i- not requ iring reop eration (124). Reexp loration is also asso-
tional equ ip m ent, and the tim e requ ired for end oscop ic ciated w ith a higher rate of p ostop erative renal failu re, pro-
harvesting have been lim iting factors. The techniqu e d oes longed m echanical ventilation, ad u lt resp iratory d istress
not ap p ear to affect vein quality (109–111). The m ost im p or- syndrome (ARDS), sepsis, atrial arrhythmias, sternal wound
tant caveats to lim iting leg w ou nd com p lications inclu d e infection, and increased length of stay (124,125). Risk factors
id entification of at-risk patients and careful hand ling of tis- for reexploration for bleeding include prolonged cardiopul-
su e w ith m inim ization of the d issection necessary to p ro- monary bypass (CPB) time ( 150 minutes), older age,
cu re the vein. smaller bod y surface area, and increasing number of d istal
With im p rovem ents in p revention of rad ial artery anastomoses (124). Emergent reexploration, occasionally at
sp asm and rep orts of good long-term p atency in rad ial the bed sid e, may be necessary in patients w ho d evelop post-
artery grafts, this cond uit has been u sed w ith increasing operative card iac tamponad e. Tamponad e occurred in 0.2%
frequ ency for coronary revascu larization (112,113). Com - of postoperative card iac patients in 2006; it should be sus-
plications associated w ith rad ial artery harvesting have pected in all patients w ho develop hypotension or decreased
been u ncom m on, w ith hand ischem ia occu rring rarely card iac output (79).
(114,115). N eu rologic com plications, includ ing sensation A thorough preoperative history shou ld id entify m ost
abnorm alities of the hand or forearm or d ecreased thu m b p atients w ith a bleed ing d iathesis and allow for d iagnostic
strength, have been reported to be as high as 30% am ong evalu ation and p lanning. Althou gh asp irin ad m inistration
patients in the early p ostoperative p eriod (116). Longer fol- has been show n to im prove graft patency p ostoperatively,
low -u p has d em onstrated that m ost of these sym ptom s it is also associated w ith an increase in postoperative blood
resolve over tim e, w ith d onor arm w eakness in 0.7% and loss and transfu sion requ irem ents (126–128). Very little can
cu taneou s p aresthesias in 3.7% of patients 8 w eeks p ostop - be d one to com bat this p roblem p reop eratively as alm ost
eratively (116,117). The incid ence of neurologic hand com - all p atients are on asp irin p rior to su rgery. Ad m inistration
plications in one large stu d y (n 786) show ed that of clop id ogrel in the p reop erative p eriod has also been
conventional scalpel and harm onic scalpel techniqu es had show n to increase the nu m ber of p atients requ iring reop er-
equ ivalent com p lication rates (11.2% using the scalp el, ation for bleed ing, increased red blood cell transfusion, and
11.0% u sing the harm onic scalpel, p 0.95) as w ell as sim i- transfu sion of other blood p rod u cts (129).
lar resolu tion rates (9.0% experienced long-term sym p tom s Periop erative ad m inistration of ap rotinin, a protease
in both grou p s). Although long-term d iscom fort in the inhibitor that w orks to inhibit fibrinolysis, w as rou tinely
hand w as low u sing both techniqu es, enou gh patients had u sed p ostop eratively as it had been show n to d ecrease the
neurologic hand sym p tom s to w arrant preoperative d is- rate of reoperation for bleed ing, postoperative chest tube
cussion of this risk (118). d rainage, and requ irement for blood transfusions (130–132).
Risk factors for the d evelopm ent of these com plications Despite its procoagulant effects, aprotinin has been show n
inclu d e d iabetes, peripheral vascu lar d isease, sm oking his- to not affect the occurrence of postoperative MI or overall
tory, and elevated serum creatinine levels. Preop erative card iac-related m ortality (133). H ow ever, d ata from large
scale stu d ies called into qu estion the safety of the m ed ica- erative renal failu re, fem ale gend er, and age 70 (144).
tion concerning increased rates of renal failu re and d eath Intraop erative risk factors for resp iratory failu re inclu d e
(134,135). Ad d itional stu d ies have refu ted those find ings, increasing card iop u lm onary byp ass tim e, w hile p ostopera-
show ing no d ifferences in ou tcom es w hen ad ju sting for tive risk factors for resp iratory failu re inclu d e the presence
patient characteristics (136). The su bject rem ains controver- of sep sis, gastrointestinal (GI) bleed ing, renal failu re, ster-
sial; ap rotinin w as su sp end ed from the m arket and is not nal w ou nd infection, p ostop erative stroke, and reoperation
available for rou tine u se. for bleed ing (143). The m ost im p ortant intervention to pre-
Limiting postoperative transfusion requirements is cru- vent resp iratory com p lications p ostop eratively is aggres-
cial not only because of the need to d ecrease the morbid ity sive p u lm onary toilet w ith early ambu lation, esp ecially in
and cost associated w ith transfu sion therapy but also the eld erly.
because transfu sion of blood prod ucts may be an ind epend -
ent pred ictor of mortality follow ing bypass surgery (137).
Other agents that have been show n to d ecrease bleed ing
■ GASTROINTESTINAL COMPLICATIONS
and the requ irement for blood transfu sions inclu d e tranex- Althou gh rare, GI com p lications follow ing coronary revas-
amic acid and aminocaproic acid (131,138,139). Althou gh cu larization are associated w ith high m orbid ity and m or-
these agents may facilitate hemostasis follow ing coronary tality. GI com p lications have been rep orted to occu r in 0.7%
revascularization, the most important factor is meticulous to 2.1% of p atients u nd ergoing coronary revascu larization
surgical technique and control of surgical bleed ing at the (145–147). The m ost com m on com p lications inclu d e GI
time of operation. bleed ing, bow el ischem ia, and p ancreatitis. Other less fre-
qu ent com p lications inclu d e p erforated d u od enal u lcer,
■ RENAL COMPLICATIONS p seu d om em branou s colitis, hep atic failu re, and cholecysti-
tis. Clostrid iu m d ifficile associated d iarrhea can be a p rob-
There is w id e variation in the literatu re regard ing the inci- lem in p atients, and increasing incid ence w ith increased
d ence of postoperative acute renal failu re follow ing coro- u se of antibiotics has been show n (148). This com plication
nary revascu larization. This inconsistency is related to is associated w ith longer ventilation tim e as w ell as both
variability in the d efinition of renal failure, ranging from an ICU and hosp ital length of stay. Overall m ortality in
isolated increase in seru m creatinine to the requ irem ent for p atients w ith p ostop erative GI com p lications is 34% to 87%
d ialysis. Acu te renal failu re, d efined as a rise in serum crea- (146,147,149). A significant cau se of the p oor ou tcom es
tinine of at least 1 m g/ d L above the baseline, has been associated w ith these com p lications is that they are often
reported in 7.9% to 14.9% of p atients follow ing revascu lar- associated w ith a d elay in d iagnosis.
ization, w ith an associated m ortality of 14% to 21.5% One of the m ost ch allen ging d iagnoses to m ake in the
(140,141). Accord ing to the STS d atabase (2006), the inci- p ostop erative CABG p atient is intestinal ischem ia. Mor-
d ence of acu te renal failu re requ iring d ialysis follow ing tality for p atients d evelop in g intestin al ischem ia p ostop -
revascu larization is 3.5% (79). Mortality associated w ith the eratively is 64% to 80% (146,147,149), an d 50% to 90% of
need for d ialysis after coronary byp ass surgery has been cases of p ostop erative intestin al ischem ia are second ary
reported to be as high as 28% (140). Risk factors for the to non occlu sive m esenteric ischem ia, w ith em bolic and
d evelopm ent of renal failu re requiring d ialysis inclu d e ele- throm botic cau ses accou nting for the rem aind er (149, 150).
vated p reop erative creatinine, increasing d u ration of car- Early recognition of signs and sym p tom s is the m ost
d iopu lm onary byp ass, cerebrovascu lar d isease, d iabetes, essen tial com p onent in the p reven tion of th e excessive
ad vanced age, p ostoperative hypotension (systolic blood m ortality associated w ith isch em ia. Th e p resen ce of p ost-
pressu re, 90 m m H g for 1 hour), LV d ysfunction, and athop erative abd om in al p ain, bloating, p ersistent ileu s, sep -
erosclerosis of the ascend ing aorta (140–142). Maintenance sis, or low er GI bleed ing shou ld p rom p t an early
of ad equ ate system ic p erfu sion d u ring and after byp ass is evalu ation for ischem ia. Unfortu nately, m any of these
the only w ay to m inim ize the risk of renal failu re follow ing p atients rem ain intu bated or sed ated in the p ostop erative
card iac surgery. p eriod , w hich m akes it m ore d ifficu lt to follow the p hysi-
cal exam ination, thu s contribu ting to a d elay in d iagnosis.
■ POSTOPERATIVE PULMONARY Seru m lactate levels m ay be u sed as an ad ju nct to p hysical
exam find ings in id entifying p atients w ith ischem ia; how -
COMPLICATIONS
ever, it shou ld be noted that seru m lactate m ay be u nreli-
Respiratory failu re and pu lm onary com plications are a sig- able in id entifying p atients w ith early intestinal ischem ia
nificant cause of m orbid ity and m ortality am ong post- and m ore likely reflects very ad vanced d isease in the set-
CABG p atients. Respiratory failu re d efined as the ting of high lactate levels. Flexible sigm oid oscop y shou ld
requ irem ent for m echanical ventilatory su p p ort for m ore be institu ted early to id entify signs of m u cosal ischem ia.
than 72 hou rs occu rs in 5.6% of p atients und ergoing iso- As w ith the p revention of renal failu re, m aintenance of
lated coronary revascularization, w ith an associated 30-d ay ad equ ate system ic p erfu sion and card iac ou tp u t both
mortality of 24.3% (143). Preoperative risk factors for p ro- intraop eratively and p ostop eratively allow s for better p re-
longed ventilation includ e unstable angina, COPD, p reop - vention of GI com p lications.
The cornerstone of treatment involves optimizing perfu- To evalu ate w hether the d ifference in ou tcom e w ou ld
sion based on the m echanism of ischem ia. Vasopressor change after su rgeons had gone throu gh the initial techni-
agents shou ld be d iscontinu ed if possible w ith optimization cal learning cu rve of OPCAB, the N ew York State registry
of the patient’s volu me statu s and card iac fu nction. If w as analyzed fu rther looking at m ore contem p orary
necrotic bow el is suspected , prompt surgical intervention is p atients (2001–2004). More OPCAB su rgeries w ere per-
essential, w ith throm boem bolectom y and resection of resid - form ed in these latter years; 13,899 p atients und erw ent
ual nonviable bow el. Early surgical intervention—d efined OPCAB su rgery. They w ere com p ared to a m atched grou p
as performance of laparotomy w ithin 6 hours of the onset of from 35,941 p atients w ho u nd erw ent on-p u mp CABG (34).
symptom s—has been show n to d ecrease m ortality in There w as no d ifference in three-year su rvival (90.1% vs.
patients w ith postoperative intestinal ischemia (149). 89.4%, p 0.20); that has been corroborated by other m ore
recent stu d ies (160,161).
■ ON-PUMP VERSUS OFF-PUMP CORONARY Review of the STS d atabase show ed a d ecrease in the
risk-ad ju sted operative mortality from 2.9% w ith conven-
ARTERY BYPASS SURGERY tional CABG to 2.3% w ith OPCAB and a d ecrease in the
A current area of controversy is the impact of off-pump risk-ad ju sted major complication rate from 14.2% to 10.6%
coronary bypass grafting on outcomes in patients requiring in 118,140 CABG proced ures perform ed from 1998 to 2000
revascularization. Although beating-heart coronary revas- (162). Resu lts from a more recent large retrospective review
cularization is not a novel concept, new er technology has of 42,477 p atients in the STS d atabase (limited to 63 N orth
im proved the ability to m anipu late the heart w hile m ain- Am erican centers w hich perform ed at least 100 OPCAB
taining hemod ynamic stability and has improved the abil- cases/ year) in the years 2004–2005 w ere similar. Multiple
ity to stabilize the isolated coronary vessel for p erform ance logistic regression analysis show ed that in the 16,245
of d istal anastomoses. A central objective of off-pump sur- p atients in the OPCAB grou p versu s the on-pum p CABG
gery is to d ecrease neurologic and neu rocognitive com plica- group the relative risk of d eath w as d ecreased (RR 0.83,
tions and to d ecrease morbid ity related to card iopulmonary 95% CI 0.69–0.98, p 0.03), stroke (RR 0.65, 95% CI
byp ass. Previou s rand omized trials comparing ou tcomes of 0.52–0.80, p 0.001), and MI (RR 0.67, 95% CI
on-pump and off-pump surgery failed to d emonstrate sig- 0.54–0.84, p 0.001) as w ell as renal failu re, sternal infec-
nificant d ifferences in postoperative neurologic inju ry, neu- tions, reop eration, atrial fibrillation, and hosp ital length of
rocognitive d ysfunction, or overall mortality (38,151–153). stay (35). A grou p w hich seem s to p articu larly benefit from
More recent stud ies have show n some improvements in the OPCAB techniqu e is the fem ale popu lation: com pared
rates of stroke. to that for on-p um p CABG they have show n im proved out-
Rand om ized trials w ith small num bers have show n a com es in d eath, MI, stroke, renal failu re, reop eration rates,
d ecreased level postoperatively of chem ical m arkers of p ostop erative atrial fibrillation, and hosp ital length of stay
myocard ial inju ry (e.g., trop onin I, creatine kinase-MB, (35,163).
myoglobin) in patients u nd ergoing OPCAB versu s those One of the p u rp orted ad vantages of off-p u m p coronary
w ho had conventional card iop ulmonary bypass (152,154). revascularization is the lim itation of blood transfu sion
The clinical significance of this find ing has not been requ irem ents (152). Off-p u m p techniqu es also prove to be
d em onstrated d irectly. Stud ies have su ggested that off- very beneficial in p atients w ith a d ifficu lt, severely athero-
pu m p su rgery m ay be associated w ith d ecreased incid ence sclerotic aorta by allow ing for limited or complete avoidance
of p ostop erative atrial fibrillation, d ecreased length of hos- of aortic manipulation (164). Improvements in technology
pital stay, and d ecreased hospital costs versu s the u se of and in ind ivid ual comfort level w ith this technique may pro-
card iop u lm onary byp ass (151–153,155). Other stu d ies have vide an ad ditional tool for dealing w ith challenging patients
failed to rep rod u ce such benefits (151,153,156–158). and may have an ad vantage over on-pump coronary revas-
Large retrosp ective stu d ies have evalu ated ou tcom es cularization in selected patients.
com p aring on-p u m p w ith off-pu m p CABG. Utilizing the
N ew York State registry, Racz et al. com p ared 9,135 p atients
w ho u nd erw ent OPCAB to 59,044 patients w ho u nd erw ent
■ SUMMARY
stand ard CABG w ith bypass from 1997 to 2000. Their find - As the use of percutaneous techniques for coronary artery
ings show ed that in spite of a d ecrease in stroke rates (1.6% d isease becom es m ore prevalent, the population of patients
vs. 2.0%, p 0.003) and reoperation for bleed ing (1.6% vs. u nd ergoing CABG has become more complex. Surgical
2.2%, p 0.001), and a shorter length of stay (5 d ays vs. p atients are now significantly old er and have more comor-
6 d ays, p 0.001) for the OPCAB grou p, the 3-year su rvival bid ities than historical cohorts. In spite of these factors,
w as better in the conventional on-p u m p CABG grou p improvements in intraoperative and postoperative man-
(89.6% vs. 88.8%, p 0.02) as w as the freed om from d eath agement and concerted efforts to im prove on quality con-
or revascu larization (84.7% vs. 82.1%, p 0.001). H ow ever, trol practices have allow ed for im provem ents in ou tcom es
these d ifferences in su rvival and freed om from revascular- for patients und ergoing coronary revascularization. As acu-
ization d isap p eared w hen they analyzed only p atients ity continues to rise, it w ill be even more challenging to d eal
from the m ost recent 2 years (159). w ith the complications associated w ith su rgical coronary
revascu larization. To meet this challenge, a m ultid iscip li- 19. John R, Choud hri AF, Weinberg AD, et al. Mu lticenter review of p re-
operative risk factors for stroke after coronary artery byp ass grafting.
nary app roach involving m ed icine, card iology, and card iac Ann Thorac Surg 2000;69(1):30–35; d iscu ssion 35–36.
surgery w ill be necessary to improve clinical management 20. Pu skas JD, Winston AD, Wright CE, et al. Stroke after coronary artery
and to foster research d irected at the treatment of patients operation: incid ence, correlates, ou tcom e, and cost. Ann Thorac Surg
2000;69(4):1053–1056.
w ith coronary artery d isease. 21. McKhann GM, Grega MA, Borow icz LM Jr, et al. Encep halop athy and
stroke after coronary artery byp ass grafting: incid ence, consequ ences,
and p red iction. Arch Neurol 2002;59(9):1422–1428.
■ REFERENCES 22. Alm assi GH , Som m ers T, Moritz TE, et al. Stroke in card iac su rgical
patients: d eterm inants and ou tcom e. Ann Thorac Surg 1999;68(2):
1. Eagle KA, Gu yton RA, David off R, et al. ACC/ AH A 2004 Gu id eline 391–397; d iscussion 397–398.
Upd ate for Coronary Artery Bypass Graft Surgery: sum m ary article: a 23. Gard ner TJ, H orneffer PJ, Manolio TA, et al. Stroke follow ing coro-
report of the Am erican College of Card iology/ Am erican H eart Asso- nary artery byp ass grafting: a ten-year stu d y. Ann Thorac Surg
ciation Task Force on Practice Gu id elines (Com m ittee to Upd ate the 1985;40(6):574–581.
1999 Gu id elines for Coronary Artery Byp ass Graft Su rgery). Circula- 24. Barbu t D, Lo YW, H artm an GS, et al. Aortic atherom a is related to ou t-
tion 2004;110(9):1168–1176. com e bu t not nu m bers of em boli d u ring coronary byp ass. Ann Thorac
2. N iles N W, McGrath PD, Malenka D, et al. Su rvival of p atients w ith Surg 1997;64(2):454–459.
d iabetes and m u ltivessel coronary artery d isease after su rgical or p er- 25. Barbu t D, Lo YW, Gold JP, et al. Im p act of em bolization d u ring coro-
cu taneous coronary revascu larization: resu lts of a large regional nary artery byp ass grafting on ou tcom e and length of stay. Ann Thorac
prospective stud y. N orthern N ew England Card iovascu lar Disease Surg 1997;63(4):998–1002.
Stu d y Group . J Am Coll Cardiol 2001;37(4):1008–1015. 26. Calafiore AM, Di Mau ro M, Teod ori G, et al. Im p act of aortic m anip u -
3. Brener SJ, Lytle BW, Casserly IP, et al. Prop ensity analysis of long-term lation on incid ence of cerebrovascular accid ents after su rgical
survival after surgical or percutaneous revascu larization in patients m yocard ial revascu larization. Ann Thorac Surg 2002;73(5):1387–1393.
w ith m u ltivessel coronary artery d isease an d h igh-risk featu res. 27. Salazar JD, Wityk RJ, Grega MA, et al. Stroke after cardiac surgery:
Circulation 2004;109(19):2290–2295. short- and long-term outcomes. Ann Thorac Surg 2001;72(4):1195–1201;
4. Coronary Artery Surgery Study (CASS). A random ized trial of coronary d iscussion 1201–1202.
artery bypass surgery. Survival d ata. Circulation 1983;68(5):939–950. 28. Davila-Rom an VG, Barzilai B, Wareing TH , et al. Intraop erative u ltra-
5. Murphy ML, H ultgren H N , Detre K, et al. Treatm ent of chronic stable sonograp hic evalu ation of the ascend ing aorta in 100 consecu tive
angina. A p relim inary rep ort of su rvival d ata of the rand om ized Vet- patients u nd ergoing card iac su rgery. Circulation 1991;84(5 Su p p l):
erans Ad m inistration coop erative stu d y. N Engl J Med 1977;297(12): III47–III53.
621–627. 29. Mills N L, Everson CT. Atherosclerosis of the ascend ing aorta and
6. Varnau skas E. Tw elve-year follow -u p of su rvival in the rand om ized coronary artery byp ass. Pathology, clinical correlates, and op erative
Eu rop ean Coronary Su rgery Stu d y. N Engl J Med 1988;319(6):332–337. m anagem ent. J Thorac Cardiovasc Surg 1991;102(4):546–553.
7. Yu suf S, Zucker D, Ped u zzi P, et al. Effect of coronary artery byp ass 30. Royse AG, Royse CF, Ajani AE, et al. Red u ced neu rop sychological
graft su rgery on su rvival: overview of 10-year resu lts from ran- d ysfu nction u sing ep iaortic echocard iograp hy and the exclu sive Y
d om ised trials by the Coronary Artery Byp ass Graft Su rgery Trialists graft. Ann Thorac Surg 2000;69(5):1431–1438.
Collaboration. Lancet 1994;344(8922):563–570. 31. Wareing TH , Davila-Rom an VG, Daily BB, et al. Strategy for the
8. The Eu ropean Coronary Su rgery Stu d y Grou p . Prosp ective ran- red u ction of stroke incid ence in card iac su rgical p atients. Ann Thorac
d om ised stu d y of coronary artery byp ass su rgery in stable angina Surg 1993;55(6):1400–1407; d iscu ssion 1407–1408.
pectoris. Second interim rep ort. Lancet 1980;2(8193):491–495. 32. Banbu ry MK, Kou chou kos N T, Allen KB, et al. Em boli cap tu re u sing
9. H offm an SN , TenBrook JA, Wolf MP, et al. A m eta-analysis of ran- the Em bol-X intraaortic filter in card iac surgery: a m ulticentered ran-
d om ized controlled trials com p aring coronary artery byp ass graft d om ized trial of 1,289 patients. Ann Thorac Surg 2003;76(2):508–515;
w ith percutaneous translum inal coronary angioplasty: one- to eight- d iscu ssion 515.
year ou tcom es. J Am Coll Cardiol 2003;41(8):1293–1304. 33. H arringer W. Captu re of particu late em boli d u ring card iac proced u res
10. H annan EL, Racz MJ, Walford G, et al. Long-term ou tcom es of coro- in w hich aortic cross-clam p is used . International Council of Em boli
nary-artery byp ass grafting versu s stent im plantation. N Engl J Med Management Stud y Group. Ann Thorac Surg 2000;70(3):1119–1123.
2005;352(21):2174–2183. 34. H annan EL, Wu C, Sm ith CR, et al. Off-p u m p versu s on-p u m p coro-
11. DiSesa VJ, O’Brien SM, Welke KF, et al. Contem p orary im p act of state nary artery bypass graft su rgery: d ifferences in short-term ou tcom es
certificate-of-need regu lations for card iac su rgery: an analysis u sing and in long-term m ortality and need for subsequent revascu lariza-
the Society of Thoracic Su rgeons’ N ational Card iac Surgery Database. tion. Circulation 2007;116(10):1145–1152.
Circulation 2006;114(20):2122–2129. 35. Pu skas JD, Ed w ard s FH , Pap p as PA, et al. Off-p u m p techniqu es bene-
12. Prabhakar G, H aan CK, Peterson ED, et al. The risks of m od erate and fit men and w omen and narrow the d isparity in m ortality after coro-
extrem e obesity for coronary artery bypass grafting ou tcom es: a stud y nary bypass grafting. Ann Thorac Surg 2007;84(5):1447–1454; discussion
from the Society of Thoracic Su rgeons’ d atabase. Ann Thorac Surg 1454–1456.
2002;74(4):1125–1130; d iscu ssion 1130–1131. 36. Roach GW, Kanchuger M, Mangano CM, et al. Ad verse cerebral ou t-
13. Lazar H L, Chip kin SR, Fitzgerald CA, et al. Tight glycem ic control in com es after coronary bypass surgery. Multicenter Stud y of Periopera-
d iabetic coronary artery byp ass graft p atients im p roves p eriop erative tive Ischem ia Research Grou p and the Ischem ia Research and
outcom es and d ecreases recu rrent ischem ic events. Circulation Ed ucation Fou nd ation Investigators. N Engl J Med 1996;335(25):
2004;109(12):1497–1502. 1857–1863.
14. van d en Berghe G, Wou ters P, Weekers F, et al. In tensive insu lin 37. van Dijk D, Keizer AM, Diep hu is JC, et al. N eu rocognitive d ysfu nc-
therap y in the critically ill p atients. N Engl J Med 2001;345(19): tion after coronary artery byp ass su rgery: a system atic review. J Thorac
1359–1367. Cardiovasc Surg 2000;120(4):632–639.
15. Fu rnary AP, Gao G, Gru nkem eier GL, et al. Continu ou s insu lin infu - 38. Van Dijk D, Jansen EW, H ijm an R, et al. Cognitive ou tcom e after off-
sion red uces m ortality in p atients w ith d iabetes und ergoing coronary pu m p and on-p um p coronary artery byp ass graft su rgery: a rand om -
artery bypass grafting. J Thorac Cardiovasc Surg 2003;125(5):1007–1021. ized trial. JAMA 2002;287(11):1405–1412.
16. Lazar H L, McDonnell M, Chip kin SR, et al. The Society of Thoracic 39. Kilo J, Czerny M, Gorlitzer M, et al. Card iop u lm onary byp ass affects
Surgeons practice guid eline series: Blood glucose m anagem ent d u r- cognitive brain function after coronary artery byp ass grafting. Ann
ing ad u lt card iac su rgery. Ann Thorac Surg 2009;87(2):663–669. Thorac Surg 2001;72(6):1926–1932.
17. Lip shu tz AK, Grop per MA. Periop erative glycem ic control: an evi- 40. H ernand ez F Jr, Brow n JR, Likosky DS, et al. N eu rocognitive ou t-
d ence-based review. Anesthesiology 2009;110(2):408–421. com es of off-pu m p versus on-pum p coronary artery bypass: a
18. Ferguson TB Jr, Hammill BG, Peterson ED, et al. A decade of change–risk prospective rand om ized controlled trial. Ann Thorac Surg 2007;84(6):
profiles and outcomes for isolated coronary artery bypass grafting pro- 1897–1903.
cedures, 1990–1999: a report from the STS National Database Committee 41. Aranki SF, Shaw DP, Ad am s DH , et al. Pred ictors of atrial fibrillation
and the Duke Clinical Research Institute. Society of Thoracic Surgeons. after coronary artery su rgery. Cu rrent trend s and im p act on hosp ital
Ann Thorac Surg 2002;73(2):480–489; discussion 489–490. resou rces. Circulation 1996;94(3):390–397.
42. Borzak S, Tisd ale JE, Am in N B, et al. Atrial fibrillation after byp ass 65. Fan K, Lee KL, Chiu CS, et al. Effects of biatrial p acing in p revention
surgery: d oes the arrhythm ia or the characteristics of the p atients proof postoperative atrial fibrillation after coronary artery bypass sur-
long hospital stay? Chest 1998;113(6):1489–1491. gery. Circulation 2000;102(7):755–760.
43. Mathew JP, Parks R, Savino JS, et al. Atrial fibrillation follow ing coro- 66. Greenberg MD, Katz N M, Iu liano S, et al. Atrial p acing for the p re-
nary artery byp ass graft su rgery: p red ictors, ou tcom es, and resou rce vention of atrial fibrillation after card iovascu lar su rgery. J Am Coll
u tilization. MultiCenter Stu d y of Periop erative Ischem ia Research Cardiol 2000;35(6):1416–1422.
Grou p. JAMA 1996;276(4):300–306. 67. Levy T, Fotop ou los G, Walker S, et al. Rand om ized controlled stu d y
44. Shore-Lesserson L, Moskowitz D, Hametz C, et al. Use of intraoperative investigating the effect of biatrial p acing in p revention of atrial fibril-
transesophageal echocard iography to pred ict atrial fibrillation after lation after coronary artery byp ass grafting. Circulation 2000;102(12):
coronary artery bypass grafting. Anesthesiology 2001;95(3):652–658. 1382–1387.
45. Ducceschi V, D’And rea A, Liccard o B, et al. Periop erative clinical pre- 68. Cochrane AD, Sid d ins M, Rosenfeld t FL, et al. A com p arison of am io-
d ictors of atrial fibrillation occu rrence follow ing coronary artery su r- d arone and d igoxin for treatm ent of su p raventricu lar arrhythm ias
gery. Eur J Cardiothorac Surg 1999;16(4):435–439. after card iac su rgery. Eur J Cardiothorac Surg 1994;8(4):194–198.
46. Alm assi GH , Schow alter T, N icolosi AC, et al. Atrial fibrillation after 69. Di Biasi P, Scrofani R, Paje A, et al. Intravenou s am iod arone vs
card iac su rgery: a m ajor m orbid event? Ann Surg 1997;226(4):501–511; prop afenone for atrial fibrillation and flutter after card iac operation.
d iscu ssion 511–513. Eur J Cardiothorac Surg 1995;9(10):587–591.
47. Cresw ell LL, Schu essler RB, Rosenbloom M, et al. H azard s of p ostop - 70. Galve E, Riu s T, Ballester R, et al. Intravenou s am iod arone in treat-
erative atrial arrhythm ias. Ann Thorac Surg 1993;56(3):539–549. m ent of recent-onset atrial fibrillation: resu lts of a rand om ized , con-
48. Lahey SJ, Cam pos CT, Jennings B, et al. H osp ital read m ission after trolled stu d y. J Am Coll Cardiol 1996;27(5):1079–1082.
card iac su rgery. Does “fast track” card iac su rgery resu lt in cost saving 71. Cam p bell TJ, Gavaghan TP, Morgan JJ. Intravenou s sotalol for the
or cost shifting? Circulation 1998;98(19 Su p p l):II35–II40. treatm ent of atrial fibrillation and flutter after card iopulm onary
49. Gu arnieri T, N olan S, Gottlieb SO, et al. Intravenou s am iod arone for bypass. Com parison w ith d isop yram id e and d igoxin in a rand om ised
the p revention of atrial fibrillation after op en heart su rgery: the Am io- trial. Br Heart J 1985;54(1):86–90.
d arone Red uction in Coronary H eart (ARCH ) trial. J Am Coll Cardiol 72. Costeas C, Kassotis J, Blitzer M, et al. Rhythm m anagem ent in atrial
1999;34(2):343–347. fibrillation–w ith a prim ary em p hasis on p harm acological therap y:
50. Daou d EG, Strickberger SA, Man KC, et al. Preop erative am iod arone Part 2. Pacing Clin Electrophysiol 1998;21(4, Pt 1):742–752.
as prophylaxis against atrial fibrillation after heart su rgery. N Engl J 73. Dim op ou lou I, Marathias K, Daganou M, et al. Low -d ose am io-
Med 1997;337(25):1785–1791. d arone-related com p lications after card iac op erations. J Thorac Cardio-
51. Dorge H , Schoend u be FA, Schoberer M, et al. Intraop erative am io- vasc Surg 1997;114(1):31–37.
d arone as p rop hylaxis against atrial fibrillation after coronary op era- 74. Liebold A, H aisch G, Rosad a B, et al. Internal atrial d efibrillation – a
tions. Ann Thorac Surg 2000;69(5):1358–1362. new treatm ent of p ostop erative atrial fibrillation. Thorac Cardiovasc
52. Red le JD, Khu rana S, Marzan R, et al. Prop hylactic oral am iod arone Surg 1998;46(6):323–326.
com pared w ith p lacebo for prevention of atrial fibrillation after coro- 75. Petersen P, Boysen G, God tfred sen J, et al. Placebo-controlled , ran-
nary artery bypass su rgery. Am Heart J 1999;138(1 Pt 1):144–150. d om ised trial of w arfarin and asp irin for p revention of throm boem -
53. Crystal E, Connolly SJ, Sleik K, et al. Interventions on p revention of bolic com plications in chronic atrial fibrillation. The Cop enhagen
postoperative atrial fibrillation in p atients u nd ergoing heart su rgery: AFASAK stud y. Lancet 1989;1(8631):175–179.
a m eta-analysis. Circulation 2002;106(1):75–80. 76. The Boston Area Anticoagu lation Trial for Atrial Fibrillation Investi-
54. Connolly SJ, Cybu lsky I, Lam y A, et al. Dou ble-blind , p lacebo-con- gators. The effect of low -d ose w arfarin on the risk of stroke in p atients
trolled , rand om ized trial of p rop hylactic m etop rolol for red u ction of w ith nonrheu m atic atrial fibrillation. N Engl J Med 1990;323(22):
hospital length of stay after heart su rgery: the Beta-Blocker Length Of 1505–1511.
Stay (BLOS) stu d y. Am Heart J 2003;145(2):226–232. 77. Arnold AZ, Mick MJ, Mazu rek RP, et al. Role of p rop hylactic antico-
55. Lee SH , Chang CM, Lu MJ, et al. Intravenou s am iod arone for p reven- agu lation for d irect cu rrent card ioversion in patients w ith atrial fibril-
tion of atrial fibrillation after coronary artery byp ass grafting. Ann lation or atrial flu tter. J Am Coll Cardiol 1992;19(4):851–855.
Thorac Surg 2000;70(1):157–161. 78. Bjerkelu nd CJ, Orning OM. The efficacy of anticoagu lant therap y in
56. Yagd i T, N albantgil S, Ayik F, et al. Am iod arone red u ces the incid ence preventing em bolism related to D.C. electrical conversion of atrial fib-
of atrial fibrillation after coronary artery byp ass grafting. J Thorac Car- rillation. Am J Cardiol 1969;23(2):208–216.
diovasc Surg 2003;125(6):1420–1425. 79. Society of Thoracic Surgeons. STS N CD Execu tive Su m m ary Sp ring
57. Seitelberger R, H annes W, Gleichau f M, et al. Effects of d iltiazem on 2007. STS Web site. Available at: http :/ w w w.sts.org/ sections/ stsna-
perioperative ischem ia, arrhythm ias, and m yocard ial fu nction in tionald atabase/ p u blications/ execu tive/ article.htm l
patients u nd ergoing elective coronary byp ass grafting. J Thorac Car- 80. Slaughter MS, Olson MM, Lee JT Jr, et al. A fifteen-year w ou nd su rveil-
diovasc Surg 1994;107(3):811–821. lance stud y after coronary artery bypass. Ann Thorac Surg 1993;56(5):
58. Kow ey PR, Taylor JE, Rials SJ, et al. Meta-analysis of the effectiveness 1063–1068.
of prophylactic d ru g therap y in p reventing su p raventricu lar arrhyth- 81. Olsen MA, Lock-Bu ckley P, H op kins D, et al. The risk factors for d eep
m ia early after coronary artery byp ass grafting. Am J Cardiol 1992; and su perficial chest surgical-site infections after coronary artery
69(9):963–965. bypass graft surgery are d ifferent. J Thorac Cardiovasc Surg 2002;124(1):
59. Pod esser B, Schw arzacher S, Zw olfer W, et al. Com bined periop era- 136–145.
tive infu sion of nifed ip ine and m etoprolol p rovid es antiischem ic and 82. L’Ecu yer PB, Murphy D, Little JR, et al. The ep id em iology of chest and
antiarrhythm ic p rotection in p atients u nd ergoing elective aortocoro- leg w ou nd infections follow ing card iothoracic su rgery. Clin Infect Dis
nary byp ass su rgery. Thorac Cardiovasc Surg 1993;41(3):173–179. 1996;22(3):424–429.
60. Toram an F, Karabu lu t EH , Alhan H C, et al. Magnesiu m infu sion d ra- 83. Lu JC, Grayson AD, Jha P, et al. Risk factors for sternal w ou nd infec-
m atically d ecreases the incid ence of atrial fibrillation after coronary tion and m id -term su rvival follow ing coronary artery bypass surgery.
artery bypass grafting. Ann Thorac Surg 2001;72(4):1256–1261; d iscu s- Eur J Cardiothorac Surg 2003;23(6):943–949.
sion 1261–1262. 84. Borger MA, Rao V, Weisel RD, et al. Deep sternal w ou nd infection:
61. Sp eziale G, Ruvolo G, Fattou ch K, et al. Arrhythm ia p rop hylaxis after risk factors and ou tcom es. Ann Thorac Surg 1998;65(4):1050–1056.
coronary artery bypass grafting: regim ens of m agnesium su lfate 85. The Parisian Med iastinitis Stu d y Grou p . Risk factors for d eep sternal
ad m inistration. Thorac Cardiovasc Surg 2000;48(1):22–26. w ou nd infection after sternotom y: a p rosp ective, m u lticenter stu d y. J
62. Parikka H , Toivonen L, Pellinen T, et al. The influ ence of intravenou s Thorac Cardiovasc Surg 1996;111(6):1200–1207.
m agnesium sulphate on the occu rrence of atrial fibrillation after coro- 86. Bu xton BF, Kom ed a M, Fu ller JA, et al. Bilateral internal thoracic
nary artery by-p ass op eration. Eur Heart J 1993;14(2):251–258. artery grafting m ay im p rove outcom e of coronary artery surgery.
63. Kap lan M, Kut MS, Icer UA, et al. Intravenou s m agnesium su lfate Risk-ad ju sted su rvival. Circulation 1998;98(19, Su p p l):II1–II6.
prop hylaxis for atrial fibrillation after coronary artery byp ass su rgery. 87. Lev-Ran O, Mohr R, Am ir K, et al. Bilateral internal thoracic artery
J Thorac Cardiovasc Surg 2003;125(2):344–352. grafting in insu lin-treated d iabetics: shou ld it be avoid ed ? Ann Thorac
64. Daou d EG, Dabir R, Archam beau M, et al. Rand om ized , d ou ble-blind Surg 2003;75(6):1872–1877.
trial of sim u ltaneous right and left atrial epicard ial pacing for preven- 88. Sofer D, Gu revitch J, Shap ira I, et al. Sternal w ou nd infections in
tion of post-open heart su rgery atrial fibrillation. Circulation 2000; patients after coronary artery bypass grafting u sing bilateral skele-
102(7):761–765. tonized internal m am m ary arteries. Ann Surg 1999;229(4):585–590.
89. Pevni D, Mohr R, Lev-Ru n O, et al. Influ ence of bilateral skeletonized 112. Acar C, Ram sheyi A, Pagny JY, et al. The rad ial artery for coronary
harvesting on occu rrence of d eep sternal w ou nd infection in 1,000 artery byp ass grafting: clinical and angiographic results at five years.
consecutive patients u nd ergoing bilateral internal thoracic artery J Thorac Cardiovasc Surg 1998;116(6):981–989.
grafting. Ann Surg 2003;237(2):277–280. 113. Maniar H S, Barner H B, Bailey MS, et al. Rad ial artery p atency: are
90. Matsa M, Paz Y, Gu revitch J, et al. Bilateral skeletonized internal tho- aortocoronary cond u its su perior to com posite grafting? Ann Thorac
racic artery grafts in p atients w ith d iabetes m ellitu s. J Thorac Cardio- Surg 2003;76(5):1498–1503; d iscu ssion 1503–1504.
vasc Surg 2001;121(4):668–674. 114. Du m anian GA, Segalm an K, Misp ireta LA, et al. Rad ial artery u se in
91. Fu rnary AP, Zerr KJ, Gru nkem eier GL, et al. Continu ou s intravenou s byp ass grafting d oes not change d igital blood flow or hand fu nction.
insulin infusion red uces the incid ence of d eep sternal w ou nd infec- Ann Thorac Surg 1998;65(5):1284–1287.
tion in d iabetic p atients after card iac su rgical p roced u res. Ann Thorac 115. Serricchio M, Gau d ino M, Tond i P, et al. H em od ynam ic and fu nc-
Surg 1999;67(2):352–360; d iscu ssion 360–362. tional consequences of rad ial artery rem oval for coronary artery
92. Brand t C, Alvarez JM. First-line treatm ent of d eep sternal infection by bypass grafting. Am J Cardiol 1999;84(11):1353–1356, A8.
a plastic su rgical approach: su p erior resu lts com p ared w ith conven- 116. Denton TA, Trento L, Cohen M, et al. Rad ial artery harvesting for
tional card iac su rgical orthod oxy. Plast Reconstr Surg 2002;109(7): coronary bypass op erations: neu rologic com plications and their
2231–2237. potential m echanism s. J Thorac Cardiovasc Surg 2001;121(5):951–956.
93. Iyer VS, Ru ssell WJ, Lep p ard P, et al. Mortality and m yocard ial infarc- 117. Bud illon AM, N icolini F, Agostinelli A, et al. Com p lications after
tion after coronary artery su rgery. A review of 12,003 p atients. Med J rad ial artery harvesting for coronary artery byp ass grafting: ou r expe-
Aust 1993;159(3):166–170. rience. Surgery 2003;133(3):283–287.
94. Cartier R, Robitaille D. Throm botic com p lications in beating heart 118. Moon MR, Barner H B, Bailey MS, et al. Long-term neu rologic hand
operations. J Thorac Cardiovasc Surg 2001;121(5):920–922. com p lications after rad ial artery harvesting using conventional cold
95. Mariani MA, Gu YJ, Boonstra PW, et al. Procoagu lant activity after and harm onic scalpel techniqu es. Ann Thorac Surg 2004;78(2):535–538;
off-pu m p coronary op eration: is the cu rrent anticoagu lation ad e- d iscu ssion 535–538.
qu ate? Ann Thorac Surg 1999;67(5):1370–1375. 119. Connolly MW, Torrillo LD, Stau d er MJ, et al. End oscop ic rad ial artery
96. Sved jeholm R, Dahlin LG, Lu nd berg C, et al. Are electrocard iograp hic harvesting: resu lts of first 300 p atients. Ann Thorac Surg 2002;74(2):
Q-w ave criteria reliable for d iagnosis of perioperative m yocard ial 502–505; d iscu ssion 506.
infarction after coronary surgery? Eur J Cardiothorac Surg 1998;13(6): 120. Patel AN , H enry AC, H u nnicu tt C, et al. End oscop ic rad ial artery
655–661. harvesting is better than the op en techniqu e. Ann Thorac Surg 2004;
97. H olm vang L, Jurland er B, Rasm u ssen C, et al. Use of biochem ical 78(1):149–153; d iscu ssion 149–153.
m arkers of infarction for d iagnosing p eriop erative m yocard ial infarc- 121. Bleiziffer S, H ettich I, Eisenhau er B, et al. N eu rologic sequ elae of the
tion and early graft occlu sion after coronary artery byp ass su rgery. d onor arm after end oscop ic versu s conventional rad ial artery harvest-
Chest 2002;121(1):103–111. ing. J Thorac Cardiovasc Surg 2008;136(3):681–687.
98. Thielm ann M, N eu hau ser M, Marr A, et al. Lip id -low ering effect of 122. Kim G, Jeong Y, Cho Y, et al. End oscop ic rad ial artery harvesting m ay
p reoperative statin therap y on p ostop erative m ajor ad verse card iac be the p roced u re of choice for coronary artery byp ass grafting. Circ J
events after coronary artery byp ass su rgery. J Thorac Cardiovasc Surg 2007;71(10):1511–1515.
2007;134(5):1143–1149. 123. H all TS, Brevetti GR, Skou ltchi AJ, et al. Re-exp loration for hem or-
99. Pan W, Pintar T, Anton J, et al. Statins are associated w ith a red uced rhage follow ing open heart surgery d ifferentiation on the causes of
incid ence of perioperative m ortality after coronary artery bypass graft bleed ing and the im p act on p atient ou tcom es. Ann Thorac Cardiovasc
su rgery. Circulation 2004;110(11 Su p p l 1):II45–II49. Surg 2001;7(6):352–357.
100. Collard CD, Bod y SC, Sh ern an SK, et al. Preop erative statin th er- 124. Dacey LJ, Mu noz JJ, Baribeau YR, et al. Reexp loration for hem orrhage
ap y is associated w ith red u ced card iac m ortality after coron ary follow ing coronary artery byp ass grafting: incid ence and risk factors.
artery byp ass graft su rgery. J Thorac Cardiovasc Surg 2006;132(2): N orthern N ew England Card iovascu lar Disease Stu d y Grou p . Arch
392–400. Surg 1998;133(4):442–447.
101. Ouattara A, Benhaou a H , Le Manach Y, et al. Periop erative statin ther- 125. Mou lton MJ, Cresw ell LL, Mackey ME, et al. Reexp loration for bleed -
ap y is associated w ith a significant and d ose-d ep end ent red u ction of ing is a risk factor for ad verse ou tcom es after card iac op erations.
ad verse card iovascu lar ou tcom es after coronary artery byp ass graft J Thorac Cardiovasc Surg 1996;111(5):1037–1046.
su rgery. J Cardiothorac Vasc Anesth 2009;23(5):633–638. 126. Verstraete M, Brow n BG, Chesebro JH , et al. Evalu ation of antip latelet
102. Paletta CE, H uang DB, Fiore AC, et al. Major leg w ou nd com plica- agents in the prevention of aorto-coronary byp ass occlu sion. Eur
tions after sap henou s vein harvest for coronary revascu larization. Heart J 1986;7(1):4–13.
Ann Thorac Surg 2000;70(2):492–497. 127. Kallis P, Tooze JA, Talbot S, et al. Pre-op erative asp irin d ecreases
103. Utley JR, Thom ason ME, Wallace DJ, et al. Preop erative correlates of platelet aggregation and increases p ost-op erative blood loss–a
im paired w ound healing after sap henou s vein excision. J Thorac Car- prosp ective, rand om ised , p lacebo controlled , d ou ble-blind clinical
diovasc Surg 1989;98(1):147–149. trial in 100 patients w ith chronic stable angina. Eur J Cardiothorac Surg
104. Garland R, Frizelle FA, Dobbs BR, et al. A retrospective aud it of long- 1994;8(8):404–409.
term low er limb com plications follow ing leg vein harvesting for coro- 128. Ferraris VA, Ferraris SP, Josep h O, et al. Asp irin and p ostop erative
nary artery bypass grafting. Eur J Cardiothorac Surg 2003;23(6):950–955. bleed ing after coronary artery byp ass grafting. Ann Surg 2002;235(6):
105. Bitond o JM, Daggett WM, Torchiana DF, et al. End oscop ic versus 820–827.
open saphenou s vein harvest: a com parison of postoperative w ound 129. Yend e S, Wu nd erink RG. Effect of clop id ogrel on bleed ing after coro-
com plications. Ann Thorac Surg 2002;73(2):523–528. nary artery byp ass surgery. Crit Care Med 2001;29(12):2271–2275.
106. DeLaria GA, H unter JA, Gold in MD, et al. Leg w ou nd com plications 130. Mu rkin JM, Lux J, Shannon N A, et al. Ap rotinin significantly
associated w ith coronary revascu larization. J Thorac Cardiovasc Surg d ecreases bleed ing and transfu sion requ irem ents in p atients receiving
1981;81(3):403–407. aspirin and u nd ergoing card iac op erations. J Thorac Cardiovasc Surg
107. Pu skas JD, Wright CE, Miller PK, et al. A rand om ized trial of end o- 1994;107(2):554–561.
scop ic versu s op en sap henou s vein harvest in coronary byp ass su r- 131. Lau p acis A, Fergu sson D. Dru gs to m in im ize p eriop erative blood
gery. Ann Thorac Surg 1999;68(4):1509–1512. loss in card iac su rgery: m eta-analyses u sin g p eriop erative blood
108. Schu rr UP, Lachat ML, Reu thebu ch O, et al. End oscop ic sap henou s transfu sion as the ou tcom e. The International Stu d y of Peri-
vein harvesting for CABG – a rand om ized , p rosp ective trial. Thorac op erative Transfu sion (ISPOT) Investigators. Anesth Analg 1997;85(6):
Cardiovasc Surg 2002;50(3):160–163. 1258–1267.
109. Crou ch JD, O’H air DP, Keu ler JP, et al. Op en versu s end oscop ic saphe- 132. Alvarez JM, Jackson LR, Chatw in C, et al. Low -d ose p ostop erative
nou s vein harvesting: w ou nd com p lications and vein qu ality. Ann aprotinin red uces m ed iastinal d rainage and blood p rod u ct u se in
Thorac Surg 1999;68(4):1513–1516. patients u nd ergoing p rim ary coronary artery bypass grafting w ho are
110. Griffith GL, Allen KB, Waller BF, et al. End oscop ic and trad itional taking asp irin: a p rosp ective, rand om ized , d ou ble-blind , p lacebo-
sap henou s vein harvest: a histologic com p arison. Ann Thorac Surg controlled trial. J Thorac Cardiovasc Surg 2001;122(3):457–463.
2000;69(2):520–523. 133. Ald erm an EL, Levy JH , Rich JB, et al. Analyses of coronary graft
111. Meyer DM, Rogers TE, Jessen ME, et al. H istologic evid ence of the patency after ap rotinin use: results from the International Mu lticenter
safety of end oscop ic sap henou s vein graft prep aration. Ann Thorac Ap rotinin Graft Patency Exp erience (IMAGE) trial. J Thorac Cardiovasc
Surg 2000;70(2):487–491. Surg 1998;116(5):716–730.
134. Shaw AD, Stafford -Sm ith M, White WD, et al. The effect of aprotinin d iop legic Arrest Stu d ies (BH ACAS 1 and 2): a p ooled analysis of tw o
on outcom e after coronary-artery byp ass grafting. N Engl J Med 2008; rand om ised controlled trials. Lancet 2002;359(9313):1194–1199.
358(8):784–793. 152. Puskas JD, William s WH , Du ke PG, et al. Off-p u m p coronary artery
135. Schneew eiss S, Seeger JD, Land on J, et al. Ap rotinin d u ring coronary- byp ass grafting p rovid es com p lete revascu larization w ith red u ced
artery bypass grafting and risk of d eath. N Engl J Med 2008;358(8): m yocard ial injury, transfu sion requ irem ents, and length of stay: a
771–783. p rosp ective rand om ized com p arison of tw o hu nd red u nselected
136. N gaage DL, Cale AR, Cow en ME, et al. Ap rotinin in p rim ary card iac p atients u nd ergoing off-p u m p versu s conventional coronary artery
su rgery: op erative ou tcom e of p rop ensity score-m atched stud y. Ann byp ass grafting. J Thorac Cardiovasc Surg 2003;125(4):797–808.
Thorac Surg 2008;86(4):1195–1202. 153. N athoe H M, van Dijk D, Jansen EW, et al. A com p arison of on-p u m p
137. Engoren MC, H abib RH , Zacharias A, et al. Effect of blood transfusion and off-p u m p coronary byp ass su rgery in low -risk p atients. N Engl J
on long-term su rvival after card iac op eration. Ann Thorac Surg 2002; Med 2003;348(5):394–402.
74(4):1180–1186. 154. Chow d hu ry UK, Malik V, Yad av R, et al. Myocard ial inju ry in coro-
138. Mongan PD, Brow n RS, Thw aites BK. Tranexam ic acid and aprotinin nary artery bypass grafting: on-pum p versus off-pum p com parison
red u ce postoperative bleed ing and transfusions d uring prim ary coro- by m easu ring high-sensitivity C-reactive p rotein, card iac trop onin
nary revascu larization. Anesth Analg 1998;87(2):258–265. I, heart-typ e fatty acid -bind ing p rotein, creatine kinase-MB, and
139. Bernet F, Carrel T, Marbet G, et al. Red u ction of blood loss and trans- m yoglobin release. J Thorac Cardiovasc Surg 2008;135(5):1110–1119,
fusion requirem ents after coronary artery bypass grafting: sim ilar effi- 1119.e1–e10.
cacy of tranexam ic acid and ap rotinin in asp irin-treated patients. 155. Ascione R, Capu to M, Calori G, et al. Pred ictors of atrial fibrillation
J Card Surg 1999;14(2):92–97. after conventional and beating heart coronary su rgery: A p rosp ective,
140. Conlon PJ, Stafford -Sm ith M, White WD, et al. Acu te renal failu re fol- rand om ized stu d y. Circulation 2000;102(13):1530–1535.
low ing card iac su rgery. Nephrol Dial Transplant 1999;14(5):1158–1162. 156. van Dijk D, N ierich AP, Jansen EW, et al. Early ou tcom e after off-
141. Su en WS, Mok CK, Chiu SW, et al. Risk factors for d evelopm ent of p u m p versu s on-p u m p coronary byp ass su rgery: resu lts from a ran-
acu te renal failu re (ARF) requ iring d ialysis in p atients u nd ergoing d om ized stu d y. Circulation 2001;104(15):1761–1766.
card iac surgery. Angiology 1998;49(10):789–800. 157. Bu ll DA, N eu m ayer LA, Stringham JC, et al. Coronary artery byp ass
142. Davila-Rom an VG, Kou chou kos N T, Schechtm an KB, et al. Athero- grafting w ith card iop u lm onary byp ass versu s off-p u m p card iop u l-
sclerosis of the ascend ing aorta is a p red ictor of renal d ysfu nction m onary bypass grafting: d oes elim inating the pu m p red u ce m orbid -
after card iac operations. J Thorac Cardiovasc Surg 1999;117(1):111–116. ity and cost? Ann Thorac Surg 2001;71(1):170–173; d iscu ssion 173–175.
143. Canver CC, Chand a J. Intraop erative and p ostop erative risk factors 158. Shennib H , End o M, Benham ed O, et al. Su rgical revascu larization in
for resp iratory failu re after coronary byp ass. Ann Thorac Surg 2003; p atients w ith p oor left ventricular function: on- or off-pu m p? Ann
75(3):853–857; d iscu ssion 857–858. Thorac Surg 2002;74(4):S1344–S1347.
144. Legare JF, H irsch GM, Bu th KJ, et al. Preop erative p red iction of p ro- 159. Racz MJ, H annan EL, Isom OW, et al. A com p arison of short- and
longed m echanical ventilation follow ing coronary artery bypass long-term ou tcom es after off-pum p and on-pu m p coronary artery
grafting. Eur J Cardiothorac Surg 2001;20(5):930–936. byp ass graft surgery w ith sternotom y. J Am Coll Cardiol 2004;43(4):
145. Peru gini RA, Orr RK, Porter D, et al. Gastrointestinal com p lications 557–564.
follow ing card iac su rgery. An analysis of 1477 card iac su rgery 160. Sabik JF, Blackstone EH , Lytle BW, et al. Equ ivalent m id term ou t-
p atients. Arch Surg 1997;132(4):352–357. com es after off-p u m p and on-p u m p coronary su rgery. J Thorac Cardio-
146. Byhahn C, Strouhal U, Martens S, et al. Incid ence of gastrointestinal vasc Surg 2004;127(1):142–148.
com p lications in card iop u lm onary byp ass p atients. World J Surg 2001; 161. Sed rakyan A, Wu AW, Parash ar A, et al. Off-p u m p su rgery is asso-
25(9):1140–1144. ciated w ith red u ced occu rrence of stroke and oth er m orbid ity as
147. H ud d y SP, Joyce WP, Pep p er JR. Gastrointestinal com plications in com pared w ith trad itional coronary artery bypass grafting: a
4473 patients w ho u nd erw ent card iop u lm onary byp ass su rgery. Br J m eta-analysis of system atically review ed trials. Stroke 2006;37(11):
Surg 1991;78(3):293–296. 2759–2769.
148. Crabtree T, Aitchison D, Meyers BF, et al. Clostrid iu m d ifficile in car- 162. Cleveland JC Jr, Shroyer AL, Chen AY, et al. Off-p u m p coronary artery
d iac su rgery: risk factors and im p act on p ostop erative outcom e. Ann byp ass grafting d ecreases risk-ad ju sted m ortality and m orbid ity. Ann
Thorac Surg 2007;83(4):1396–1402. Thorac Surg 2001;72(4):1282–1288; d iscu ssion 1288–1289.
149. Ghosh S, Roberts N , Firm in RK, et al. Risk factors for intestinal 163. Pu skas JD, Kilgo PD, Ku tner M, et al. Off-p u m p techniqu es d isp ro-
ischaem ia in card iac su rgical p atients. Eur J Cardiothorac Surg 2002; p ortionately benefit w om en and narrow the gend er d isparity in out-
21(3):411–416. com es after coronary artery byp ass su rgery. Circulation 2007;116(11
150. Pinson CW, Alberty RE. General su rgical com p lications after car- Su pp l):I192–I199.
d iopu lm onary byp ass su rgery. Am J Surg 1983;146(1):133–137. 164. Sharony R, Grossi EA, Saunders PC, et al. Propensity case-matched
151. Angelini GD, Taylor FC, Reeves BC, et al. Early and m id term ou tcom e analysis of off-pump coronary artery bypass grafting in patients with
after off-pum p and on-p u m p su rgery in Beating H eart Against Car- atheromatous aortic disease. J Thorac Cardiovasc Surg 2004;127(2):406–413.
CHAPTER
28
Complications in Valvular
Cardiac Surgery
Gorav Ailawadi
■ INTRODUCTION These p atients shou ld be considered for anticoagu lation

therap y d esp ite having a tissu e p rosthesis. Stru ctu ral valve
More than 100,000 operations for card iac valve repair or d egeneration eventu ally lead ing to valve failu re is the m ost
replacement are performed in the United States, and more im portant long-term com plication of the bioprosthetic
than 1 million valve operations are perform ed w orld w id e valve. The risk of valve failu re increases over tim e, and this
each year. The earliest valve surgery, closed mitral valvo- rate is accelerated in both you nger p atients and those on
tomy, w as performed through a thoracotom y w ithout the chronic d ialysis. The p robability of stru ctu ral failure w ith
use of card iopu lmonary bypass. With the ad vent of the car- cu rrently available p orcine and bovine p ericard ial valves
d iopulmonary bypass circuit, marked improvements have increases beginning at ap p roxim ately 10 to 12 years after
been mad e in the surgical treatment of patients w ith valvu - op eration. The life exp ectancy of these valves, w ith new
lar heart d isease. Im provem ents in card iac protection, pros- anticalcification fixation techniqu es is thou ght to be in the
thetic (mechanical and bioprosthetic) heart valves, and 15 to 20 year range (4–8).
valve reconstructive/ repair techniques all have contributed
to improved outcomes (1,2). In ad d ition, the w id espread
use of intraop erative transesop hageal echocard iography
■ Mechanical valves
(TEE) and upd ated guid elines for timing of surgical inter- Mechanical valves have the p otential for ind efinite long-
vention have further stand ard ized outcomes related to term d urability but have increased risk of throm boem -
valve surgery (1,2). The recognition of complications related bolism and the risk of bleed ing second ary to the need for
specifically to valvular surgery has led to the greatest anticoagu lation (9). Rates of throm botic com p lications are
im provem ent in valvular su rgery ou tcom es (Table 28.1). low (1% to 3%) w hen the p atients are ad equ ately anticoag-
u lated . H ow ever, anticoagu lation-related bleed ing rem ains
one of the m ost com m on cau ses of valve-related m orbid ity
■ PROSTHETIC HEART VALVES (1% to 3% p er p atient-year) and mortality (0.1% to 0.5% per
The p rosthetic valves available tod ay are of tw o p rim ary p atient-year), as safe, stable, and effective anticoagu lation
categories: bioprosthetic (biologic tissue) and m echanical is often d ifficu lt to achieve (10). Ongoing trials are u nd er-
valves. Tissu e valves includ e p orcine (stented and stent- w ay, evalu ating the u se of asp irin alone in p atients w ith
less) and p ericard ial (bovine or equine) valves. In ad d ition m echanical valves.
to p rosthetic valves, allografts (hu m an cad averic hom o-
grafts) and au tografts (pu lm onic valve) can be used in ■ Prosthetic valve endocarditis
either the aortic or the m itral position (3). The m echanical
prostheses inclu d e single tilting d isc and bileaflet valves. Prosthetic heart valves carry an increased risk for the
d evelop m ent of end ocard itis that can be p recip itated by
any cau se of transient bacterem ia. Prosthetic valve end o-
■ Bioprosthetic valves card itis (PVE) encom p asses 15% to 30% of all cases of end o-
card itis, is rep orted in 1% to 2% of all valve im p lants, and is
A significant ad vantage of tissue valves is the avoid ance of
associated w ith a m ortality rate higher than that of native
the need for lifelong anticoagulation. These valves have a
valve end ocard itis (11,12). PVE that occu rs in the early
very low throm boem bolic com plication rate; how ever, risk
p ostoperative period is frequ ently d u e to Staphylococcus
d oes exist in patients w ith atrial fibrillation or w ith an
epidermidis, either d u e to a break in techniqu e in the operat-
enlarged left atriu m , a history of previous em boli, an atrial
ing room or from skin contam ination. Late-onset PVE is
clot, or significantly red uced left ventricular (LV) function.
related to bacterem ic seed ing of the valve. Com m on portals
of entry inclu d e d ental p roced u res, op erations, gastroin-
testinal end oscop y, intravenou s catheter contam ination,
Gorav Ailawadi: University of Virginia, Charlottesville, intravenou s d ru g abu se, and infections of the skin, lu ngs,
VA 22908. bow el, and the u rinary tract.
310
Chapter 28 • Complications in Valvular Cardiac Surgery 311
Table 2 8 .1 Com p lica t ion s of va lve su r ger y em boli from tricu sp id valve (TV) end ocard itis can p rod u ce
p atchy infiltrates on chest rad iograp h. Echocard iogram
General Complications m ay show a rocking m otion of the p rosthesis and the pres-
• Structural valve degeneration
ence of vegetations or a new onset of a p aravalvu lar leak.
• Anticoagulation-related bleeding
Often TEE is need ed to m ake the d iagnosis.
• Mechanical valve thromboembolism
• Prosthetic valve endocarditis Althou gh carefu lly selected antim icrobial therap y, sp e-
• Paravalvular leak cific for the infecting organism s, is im p ortant in the care of
• Supraventricular arrhythmias PVE, it is rare that antim icrobial therap y alone w ill cu re
• Heart block PVE. Most p atients requ ire su rgical rem oval of the valve
• Low cardiac output and valve rep lacem ent. Ind ications for acu te su rgical
• Debris, fat, or air embolism intervention in PVE inclu d e the p resence of new -onset
Procedure-Specific Complications congestive heart failu re, com p lete heart block (CH B), or
Aortic valve complications card iogenic shock. Su rgical intervention should not be
• Aortic-ventricular dehiscence d elayed in the p resence of acu te infective PVE w hen con-
• Mitral leaflet detachment gestive heart failu re ensu es. H ow ever, su rgical interven-
• Occlusion of coronary artery ostia tion is futile if com plications of the infection (such as severe
• Inadequate myocardial preservation em bolic cerebral d am age) or other com orbid cond itions
• Aortic wall dissection or embolization m ake the p rosp ect of recovery rem ote.
• Atrioventricular node block
Anesthesia, intraop erative m onitoring, card ioplegia,
Mitral Valve Replacement Complications and exp osu re of the valve are sim ilar to other valvular pro-
• Atrioventricular groove rupture ced u res. Excision of the valve and d ebrid em ent of the
• Circumflex artery injury annu lu s and abscesses m u st be m eticu lou s and extensive.
• Coronary sinus injury
All necrotic and infected tissu e m u st be rem oved . After
• Posterior myocardial perforation
local antibiotic irrigation, the annu lu s and areas of tissu e
• Aortic valve cusp entrapment
• Mitral valve prosthesis leaflet entrapment/suture looping loss can often be reconstru cted by u sing au tologou s p eri-
• Ventricular output failure card iu m or aortic hom ograft (13).
• Mechanical valve thrombosis Abscess form ation is the m ost com m only rep orted
• Late cardiac tamponade PVE m an ifestation ; it occu rs in 20% of cases and is m ost
Mitral Valve Repair Complications often cau sed by S. aureus. Enterococcus sp ecies have been
• Residual mitral stenosis or regurgitation rep orted in 5% to 17% of the cases, and gram -negative rod
• Persistent mitral regurgitation infections are rare (1% to 9%). Other second ary m anifesta-
• Left ventricular (LV) outflow obstruction tions of end ocard itis inclu d e aortic m ycotic infections, car-
• Hemolysis d iac cond u ction d efects, sinu s of Valsalva aneu rysm s, and
Tricuspid Valve Complications valve throm bosis. Fu ngal infections occu r m ore frequently
• Persistent right ventricular failure in patients w ith p rosthetic valves w ho are im m u nocom pro-
• Complete heart block m ised or intravenou s d ru g u sers. Fu ngal vegetations, d u e
• Recurrent or residual tricuspid regurgitation to their bu lky size, can p rod u ce valvu lar stenosis (14–16).
Transcatheter Aortic Valve Complications S. aureus and fu ngal infections are p articu larly aggressive
• Vascular injury and typ ically shou ld be treated w ith su rgical valve rem oval
• Bleeding from LVapex and rep lacem ent u rgently. Other organism s are often viru -
• Inappropriate placement of valve lent, and the tim ing of su rgery is d ictated by their clinical
• Rupture of aortic annulus p resentation.
• Occlusion of coronary artery ostia Postop erative care shou ld inclu d e at least 6 w eeks of
• Heart block intravenous antibiotics. H ospital m ortality is related pri-
m arily to ongoing sep sis, m u ltisystem organ failu re, or fail-
u re to erad icate the local infection follow ed by recu rrent
p erivalvu lar leak. Valve rep lacem ent in hem od ynam ically
Physical exam ination, m icrobiological resu lts, labora- stable p atients w ith PVE has a favorable ou tcom e in 80% to
tory testing, and im aging proced u res are all u sefu l to d iag- 95% of cases (17). The reinfection rate overall is u ncom m on
nose PVE. The m ost com m on presenting sym p tom s for and ranges from 1% to 10%.
PVE are fever, fatigu e, m alaise, and d yspnea. Pyrexia,
new ly noted heart m urm ur, and m icroscopic hematu ria are
frequ ent clinical signs. Thirty percent of patients p resent
■ Paravalvular leak
w ith sep tic em boli, w hich can involve the spleen, kid neys, Paravalvular leak is an u ncommon complication w ith cur-
cerebral vascu lature, and coronary system . Blood cu ltu res rent su rgical techniqu es. The incid ence of paravalvu lar leak
are the m ainstay of d iagnosis and are positive for bac- for both mechanical and biologic valves is approximately
terem ia in m ore than 90% of cases. Septic p u lm onary 0% to 1.5% p er patient-year of valve life. Paravalvular leak
trad itionally w as consid ered slightly m ore com m on w ith

the bileaflet valve than w ith the p orcine valve becau se of a
less bu lky sew ing ring (18). H istorically, the u se of p led -
geted su tu res to seat the valve w as thought to d ecrease the
risk of p aravalvu lar leak. Recently, our grou p has d em on-
strated sim ilarly low p aravalvu lar leak rates w ith a non-
pled geted su tu re techniqu e (19).
Calcium
particles
■ Atrial arrhythmias
Atrial arrhythm ias, prim arily atrial fibrillation and atrial
flutter, occu r in 10% to 40% of patients after valve su rgery
and can contribu te to neu rologic morbid ity. The u su al
onset is 1 to 3 d ays after operation, w ith a peak incid ence at
48 hou rs; how ever, arrhythm ias m ay occu r at any tim e,
includ ing shortly after d ischarge. Increasing age is the
most consistent pred isposing factor; other cond itions
includ e a history of rheu m atic fever, aortic cross-clam p
tim e and card iop u lmonary bypass tim e, and abru pt stop - FIGURE 28.1. A sponge placed in the left ventricle during debridement of
the aortic or mitral valve annulus can catch the debris. This may prevent small
page of -blocking agents. Acid osis, hypokalem ia, or pieces from becoming lodged in the spaces along the wall of the ventricle,
hyp oxem ia may contribute to the onset of the arrhythm ia only to embolize once contractile cardiac function resumes.
and shou ld be corrected before initiating d efinitive therap y.
Amiod arone is the first-line agent for both rate control and
conversion to sinu s rhythm in these p atients p ostopera- ventricle to the aorta. If the d efect is large, a bovine pericar-
tively (20,21). d ial p atch can be u sed to close the d efect before p lacing the
valve su tu res.
■ COMPLICATIONS OF AORTIC VALVE SURGERY Occlusion of the Coronary Arteries

Du ring aortic valve rep lacem ent, the right and left m ain
■ Complications related to the aortic valve annulus coronary os are visible. Care m u st be taken d u ring valve
Calcific d egeneration is the most common cause of aortic d ebrid em ent that calciu m and d ebris d o not occlu d e or
valve stenosis. Calcification is nearly alw ays present both in em bolize into the coronary arteries. Im p ortantly, as valve
the aortic valve leaflets and the aortic annulus at the time of su tu res are p laced , they shou ld be p laced low enough
operation, particularly in the eld erly patient. The native below the os to avoid the prosthetic valve annu lu s from
valve is excised by using scissors, knife, or a rongeur to obstru cting the coronary arteries. The com m issu res of the
remove all calcium allow ing the prosthetic valve to seat p rosthetic valve should m atch the native trileaflet aortic
properly in the annulus. Inadequate debrid ement of the valve such that the stru ts of the prosthetic valve d o not
leaflets can predispose to paravalvular leaks as the pros- obstru ct the coronary arteries. Occlu sion of the coronary
thetic valve may not be opposed to the aortic annulus or artery m anifests are ventricu lar arrhythm ias and low car-
may result in d ebris in the LV cavity or coronary arteries. To d iac ou tp u t. TEE can be u sed to visu alize flow in the coro-
avoid any embolism of this d ebris, copious rinsing is critical; nary ostia. If an occlu d ed coronary artery is d iscovered ,
a sponge placed in the ventricle can be helpful (Fig. 28.1). rep lacem ent of the valve is u su ally m and ated . Another
On the other extrem e, vigorou s d ebrid em ent of calciu m op tion is to p erform a coronary artery byp ass to the
in the aortic annu lu s can resu lt in d etachm ent of the ante- affected coronary system w ith an internal thoracic artery or
rior m itral leaflet, w hich is in continuity w ith the aortic saphenou s vein graft.
valve annu lu s p osteriorly. This resu lts in an opening from
the aortic root into the left atrium . This d efect shou ld be ■ Complications related to
rep aired w ith p led geted su tu res throu gh the anterior
myocardial preservation
leaflet of the m itral valve and the aortic valve annu lu s.
These su tu res are then u sed to secu re the prosthesis. Sim i- Inad equate m yocard ial preservation d u ring the aortic
larly, d ebrid em ent of calciu m in the annu lu s w all can resu lt valve replacem ent proced u re is the m ost com m on cau se of
in a d isru p tion of the ventriculoaortic ju nction. If u nrecog- p ostop erative ventricu lar d ysfu nction. Most su rgeons
nized , this w ill lead to ventricu loaortic d issociation and em p loy hyp otherm ic card iop legic p reservation d u ring aor-
profuse arterial bleed ing below the level of the valve. tic valve rep lacem ent. Concom itant coronary artery occlu-
When overly aggressive d ebrid em ent is perform ed and sive d isease can resu lt in uneven d istribu tion of the
d isrup tion of the annu lu s is of concern, pled geted su tu res card iop legia solu tion. For this reason, m ost su rgeons use
shou ld be u sed to rep air the annu lu s to reap p roxim ate the retrograd e card ioplegia as an ad ju nct to protection or as the
sole m ethod to d istribute the card ioplegia. H ow ever, retro- One ad d itional m echanism of bleed ing from the aorto-
grad e card ioplegia d oes not d istribute ad equ ate d oses of tomy can occu r if the aortotomy is p laced too low. Biopros-
card iop legia to the right coronary system . As su ch, right thetic valves have stru ts at the location of the com m issu res
heart d ysfunction can ensu e w ith inad equ ate protection of of the valve that can p rotru d e and abu t the aorta. When the
the right heart. This comp lication can be obviated by aortotom y is p laced too low, the stru t can abut the su tu re
ad m inistering hand held card ioplegia into the right coro- line and lead to acute or late breakd ow n of the aortotom y,
nary os after the aorta has been op ened to perform the aor- resu lting in m ajor hem orrhage. As su ch, the aortotom y
tic valve rep lacem ent. The u se of top ical cooling solu tions shou ld be p laced at least 2 cm above the annu lu s of the aor-
arou nd the heart d u ring aortic valve replacem ent also tic valve. N ew er biop rosthetic valves often have a low er
help s to ensu re m yocard ial preservation, especially of the p rofile w ith shorter stru ts su ch that the risk of this occu r-
right ventricle (RV), w hich is m ost prone to w arm ing from ring is less frequ ent. When the aortotom y is p laced too low,
operative lights. One effective rou tine is to m easu re the and there is concern that a stru t m ay erod e into the sutu re
sep tal tem p eratu re continu ou sly d u ring op eration and line, the aortotom y can be closed w ith a bovine pericard ial
maintain it at 10 C to m onitor the ad equ acy of m yocard ial p atch to d ecrease the risk the stru t w ill abu t the aorta.
preservation (22). Card ioplegia shou ld be ad m inistered at
regu lar intervals of 15 to 20 m inu tes or on the basis of sep -
tal tem p eratu re.
■ Atrioventricular node block
The atrioventricular (AV) nod e is located in the m em bra-
■ Complications related to the aorta nou s sep tu m , w hich is located ju st below the junction of
the right coronary cu sp and the noncoronary cu sp of the
and the aortotomy
aortic valve. Great care m u st be taken w hen placing valve
Either a transverse or an obliqu e aortotom y is u sed to p ro- sutu res in this location as the AV nod e m ay be d am aged by
vid e access to the valve. Patients w ith bicu sp id aortic p lacem ent of d eep stitches, overly aggressive d ebrid em ent,
valve d isease have thin and often aneu rysm al ascend ing or annu lar abscess (sim ilar to Fig. 28.2). In m ost circu m -
aortas. In ad d ition, calcification of the ascend ing aorta fre- stances, AV cond u ction d istu rbances at the conclu sion of
qu ently accom p anies calcific d egeneration of the aortic the p roced ure d o not requ ire the placem ent of perm anent
valve, esp ecially in eld erly p atients. A calcified or even p acing electrod es as the m ajority of temp orary AV nod e
p orcelain aorta m ay p reclu d e safe cannu lation of the d ysfu nction im m ed iately follow ing aortic valve rep lace-
ascend ing aorta for card iop u lm onary byp ass. In these m ent is transient. Ed em a from the p roced u re itself can
instances, the risk of aortic inju ry or stroke is exceed ingly cau se tem p orary AV cond u ction block, w hich resolves
high and alternative cannu lation sites su ch as the axillary w ithin the first p ostop erative w eek (23,24). The incid ence
or fem oral artery shou ld be em p loyed . In ad d ition, calci- of p acem aker requ irem ent follow ing aortic valve surgery is
fied p laqu es can fractu re w hen the aortic cross-clam p is on the ord er of 3% to 5% and is typ ically not perform ed
ap p lied , cau sing arterial em bolization or later d issection u ntil at least a w eek after su rgery.
of the aorta. With a severely d iseased aorta or p orcelain
aorta that is too calcified for the safe ap p lication of a cross-
clam p , the techniqu e of d eep hyp otherm ia and circu latory
■ Paravalvular leak
arrest m ay be a p referable op tion. Segm ental end arterec- Paravalvu lar leak resu lts in aortic insufficiency and can
tom y and d ecalcification are occasionally requ ired to su c- cau se hem olysis, cau se recu rrent sym p tom s of heart fail-
cessfu lly close the aorta. Aortas that are friable or calcified u re, or lead to end ocard itis. Most often, p aravalvular leaks
shou ld be closed by u sing strip s of felt to bu ttress the are created in the op erating room d u ring valve insertion.
su tu re line. Thu s, care m u st be taken to ensu re that su tu res (w hether
Extrem e care m u st be taken to close the aortotom y as p laced as sim ple interru pted or horizontal m attress) have
this can be a challenging area to rep air shou ld bleed ing m inim al travel betw een su tu res. In ad d ition, d eep bites of
occu r after the cross-clamp is rem oved . Typ ically, closu re of the annu lu s and aorta are necessary to ensu re the su tu res
the aortotom y is p erform ed w ith a tw o-layer closu re. Tak- d o not p u ll throu gh. Finally, sizing the valve appropriately
ing bites that are too d eep can result in excessive tension and avoid ing p lacing too large a valve given the annulu s
and tearing of the aorta once system ic pressure is p resent. size w ill allow the p rosthetic valve to seat appropriately in
Bleed ing from the aortotom y can be hand led in several d if- or above the annu lu s. These maneu vers w ill m inim ize the
ferent m anners. Repair of the aorta can be as sim p le as risk of p aravalvu lar leak.
placem ent of ad d itional horizontal m attress p led geted Paravalvular leak is d iagnosed by TEE. In ad d ition, a
su tu res across the aortotom y to bu ttress the closu re to paravalvular leak may be present if there is evid ence of
reclam p ing the aorta and replacing the aorta. Another pulsatility w ith the heart beating even w hen on full car-
op tion is coverage of the aortotom y w ith bovine p ericard ial d iopulmonary bypass. This w ould indicate that blood is
patch, w hich can be p articular useful if there is concern for regurgitating across the aortic valve and ejecting w ith each
placing ad d itional tension on the closu re, w hich rep air cardiac cycle. Small paravalvular leaks are often related to
stitches often d o. small gaps betw een sutures and often resolve after heparin
FIGURE 28.2. Suture injuries to

structures surrounding the mitral valve
annulus. Improper placement of sutures
in the annulus can damage the left cir-
cumflex artery, aortic valve, atrioventric-
ular node, or coronary sinus.
Aortic valve
Atrioventricular node
Artery to
atrioventricular node
Mitral valve annulus
Left circumflex
coronary artery Coronary sinus
reversal. Larger paravalvular leaks often require rearresting stretching of the LV by the p rosthesis or by a stru t. It is
the heart and repair. This can typically be performed w ith m anifested as p rofu se bright-red blood em anating from
additional pledgeted sutures placed between the aorta and behind the heart. Becau se of the p otential for this com p lica-
valve annulus. Often, these are most easily placed from tion, the ap ex of the heart shou ld not be lifted after MVR is
below the valve if a bioprosthetic valve is placed. Mechani- p erform ed . As su ch, concom itant coronary artery bypass
cal valve paravalvular leaks require placing sutures from the shou ld be p erform ed p rior to m itral valve su rgery. Treat-
adjacent aorta to the valve sewing ring. If unable to ade- m ent requ ires reinstitu tion of card iop u lm onary byp ass
quately assess or repair the paravalvular leak, rem oval and rem oval of the valve p rosthesis. The p erforation is located ,
reinsertion of the valve may be needed. and rep air m ay be d one w ith the u se of Teflon or pericar-
d ial strip s, both externally and internally. With com m on
techniqu es of p reservation of the p osterior m itral leaflet
■ COMPLICATIONS OF MITRAL VALVE SURGERY
and p ap illary m u scles, this com p lication is rare.
■ Injury to the circumflex artery
The anatom y of the m itral valve is su ch that several m ajor
■ Atrioventricular groove dissociation
stru ctu res lie in near this im portant valve. The circum flex AV d issociation is a d read ed and often fatal com plication.
coronary artery lies in the AV groove along the left sid e of This is an extrem e form of posterior LV rup tu re w here a
the valve and can be inju red or occlu d ed by p lacem ent of p ortion or the entire posterior left atrium separates from
the m itral valve su tu res too d eep ly beyond the annu lu s the left ventricle. The risk of this occu rrence is greatest in
d u ring valve rep lacem ent (Fig. 28.2). This com plication p atients w ith extensive calcification in the posterior m itral
presents as d ecreased card iac ou tput, poor LV lateral w all annu lu s and leaflet. This find ing is com m on in eld erly
motion on intraop erative echocard iogram , or bleed ing p os- p atients und ergoing m itral valve su rgery and is evid ent by
teriorly from the heart. Correction requ ires the reinstitu tion p reop erative im aging, inclu d ing echocard iography and
of card iop u lm onary bypass, rem oval of the stitch, and , card iac catheterization. Chest com p u ted tom ography w ith-
occasionally, a sap henou s vein bypass graft to the circu m - ou t intravenou s contrast can be u sefu l in qu antifying the
flex coronary. Carefu l placem ent of sutu res at the ju nction d egree of p osterior m itral annu lar calcification (also know n
of the m itral valve annu lu s and the valve leaflet p revents as MAC).
this com p lication. Circu m flex artery inju ry is less com m on AV d issociation is usually related to vigorou s traction
d u ring m itral valve repair as the su tu res are placed p arallel or d ebrid em ent of the p osterior leaflet of the valve or to cal-
to the valve rather than across the annu lu s as they are d u r- ciu m excision in a calcified p osterior leaflet. This can cause
ing m itral valve replacem ent (MVR). sep aration of the AV groove, lead ing to m assive hem or-
rhage u p on sep aration from card iop u lm onary bypass. This
com p lication is p revented by u nd erstand ing the p athologic
■ Posterior myocardial perforation p rocess of calcification of the m itral annu lu s and avoid ing
Myocard ial ru p tu re is a catastrop hic com p lication of m itral rup tu re by either placement of traction su tures on the ed ge
valve su rgery. The incid ence is rare (0.5% to 2%) and occu rs of the p osterior leaflet or by very carefu l calciu m d ebrid e-
d u ring MVR. This com plication is caused by perforation or m ent only in isolated sp ots. A safer p roced u re m ay be to
attach the p rosthesis to the atrial w all, leaving the entire

calcified m ass intact. This approach m ay result in a sm aller
valve area bu t a successful operation (25). When this com -
p lication occu rs, valve p rosthesis is rem oved and the ven-
tricle is reapproxim ated to the left atriu m w ith felt strip s.
Often, a p ericard ial patch is used to cover the d efect and
the valve su tu res are now p laced into the pericard ial patch.
Embedded
N evertheless, this com plication carries a high m ortality. strut
■ Embolus A
Em boli from the heart can be d ebris from valve d ebrid e-
m ent, fat p articles, or air. This com plication resu lts w hen
there is failu re to rem ove all d ebris, often from an exten-
sively calcified valve or throu gh technical errors that allow
air to rem ain in the LV outflow tract. Em bolism typ ically
occu rs on rem oval of the cross-clam p and resu m p tion of Loose chordae
norm al card iac ejection. Prevention is critical and involves
cop iou s irrigation of the LV to rem ove all d ebris. Air
em bolism m ay be prevented by an LV vent, an aortic root
asp irating vent, or need le-venting the LV apex. Rem oval of
all air can be confirm ed by the intraop erative TEE (26,27). B
FIGURE 28.3. Dysfunction of prosthetic valves due to interference from
periannular structures. A: Mitral valve struts can become entrapped along the
■ Entrapment of the noncoronary cusp wall of the ventricle and in the valve remnant, chordae, or papillary muscles.
of the aortic valve B: Remnants of the papillary muscles preventing full closure of the valve.
Althou gh rare, this can occu r in the area of 10 o’clock to

12 o’clock of the m itral valve, near the anterolateral com -
m issu re of the m itral valve. At this point, the com m issu re is removed . The valve is then rep laced . Often, the placement
very close to the aortic valve’s noncoronary cu sp , and this of sutures in an everting fashion (from atrium to ventricle)
cu sp may be entrap p ed if the m itral valve su tu re is p laced allow s the valve to seat w ithin the annulus, p reventing
too d eep ly (Fig. 28.2). This com plication m ay be d iagnosed leaflet tissu e from obstructing the m echanical leaflets.
only after the rem oval of the aortic cross-clam p, w hen the
heart d ilates becau se of severe aortic regu rgitation and ■ Acute valve dysfunction due to suture looping
w hen aortic insu fficiency is observed on TEE. Avoid ing
excessively d eep bites can prevent entrap ment. Treatm ent This com p lication cau ses early biop rosthetic valve d ys-
of entrap m ent requires reinstitution of card iop u lm onary fu nction and severe m itral regurgitation (MR) from im m o-
byp ass, re–cross-clam ping, rem oval of the m itral p rosthe- bility of a leaflet. Leaflet loop ing is p reventable by carefu lly
sis, and resu tu ring the area at this point. In som e cases, the p u shing the valve d ow n d u ring insertion or by use of a
aortic root m ay need to be opened and the aortic valve d ental m irror to inspect the valve stru ts and ensu re that no
insp ected , rep aired , or even replaced . su tu re is loop ed over them before the valve su tu res are tied
d ow n. Failu re to d o so w ill resu lt in a large paravalvu lar
leak. Correction of this com p lication requ ires rem oving
■ Leaflet entrapment by retained valvular tissue and reim p lanting the valve.
Many mechanical valves involve the opening and closing of
either single or d ouble leaflets. With these valves, care must
be taken that retained native valve structures, chord s, or
■ Low cardiac output
tips of p apillary m u scles d o not interfere w ith the leaflet Low card iac ou tput follow ing MVR is a frequent comp lica-
action (Fig. 28.3). Tissue retention can prod uce significant tion that has been d ocu m ented since this p roced u re’s
obstru ction or regurgitation. Echocard iograp hy is the best incep tion. It has also been one of the m ost d ifficu lt prob-
w ay to d emonstrate valve malfu nction. This complication is lem s to treat becau se it has m any cau ses. In p atients w ith
prevented by u sing proper supra-, sub-, or annular sutu ring MR, d ep ression of card iac p erform ance is com m on after
technique. To ensure that leaflets open and close w ithout initial valve rep lacem ent. The norm ally cone-shap ed ven-
interference at implantation, a cotton-tipped sw ab or rubber- tricle assu m es a sp herical shap e if there is rem oval of the
shod instru ment can be used to test the valve. To fix this papillary muscle-annular continuity. This concept was first
problem , the m itral valve is rem oved , and the tissu e that promulgated in 1964, and laboratory and clinical studies have
prevents opening and closing below the valve shou ld be su bstantiated that m aintaining p ap illary m u scle-annu lar
continu ity is im portant for the m aintenance of norm al car- d efin itive d iagn osis is m ad e by flu oroscop y. Alth ou gh
d iac ou tp u t and LV shape. The norm al LV geom etric rela- im m ed iate op eration m ay be requ ired , throm bolytic
tionship can be best m aintained by mitral valve repair or, if therap y is an op tion if the p atient is not m oribu nd . In
that is not p ossible, by p reserving the p osterior leaflet and p atients in extrem is, insertion of a p ercu taneou s LV assist
papillary m u scles w ith the insertion of a totally intact valve d evice su ch as a Tand em H eart (Card iac Assist, Pittsbu rgh,
into the m itral ap p aratu s. The p rognosis for the patient Pennsylvania) w ill allow correction of acid osis and card iac
w ith low card iac ou tp u t from loss of LV geom etry is grave ou tp u t and allow for m ore op tim al hem od ynam ics at the
and accou nts for su bstantial early and late m ortality fol- tim e of reop eration (30). At operation, the prosthesis is
low ing MVR (28). Other causes of low card iac ou tp u t inspected and can be reim p lanted , or a throm bectom y m ay
includ e inad equ ate m yocard ial protection, injury to the cir- be su fficient. If there is an obviou s cau se for the throm bosis
cu m flex artery, or resid ual MR. that can be fixed , su ch as an im p inging su tu re, the clot can
be rem oved and the LV irrigated cop iou sly to ensu re com -
p lete throm bu s rem oval. If not, the valve shou ld be re-
■ Paravalvular leak rep laced (31). Prior to the op eration, the d ecision m ust be
Paravalvu lar leak, early or late, prod u cing severe regu rgi- m ad e w ith the p atient w hether a biop rosthetic or m echani-
tation m ay occu r in p atients w hose tissue is friable, in cal valve shou ld be inserted , on the basis of the patient’s
patients w ith end ocard itis, or in patients w ho have exten- ability to take and com p liance w ith anticoagu lation.
sive calcification. Patients have a loud holosystolic m u r-
mu r. The d iagnosis is m ad e by echocard iogram and a rise
in left atrial p ressu re w ith a prom inent V w ave. Using p led - ■ Late tamponade
geted su tu res can p revent this com plication, particu larly Patients w ho have und ergone recent MVR requiring anti-
w hen fragile or m inim al annu lar tissu e is fou nd . If there is coagu lation m ay have late card iac tam p onad e. This is d u e
an abscess, a p ericard ial or Teflon bolster m ay be necessary to accu m u lation of blood in the p ericard ial sp ace. The d iag-
to im p rove the fixation of the valve. Testing the valve p rior nosis shou ld be consid ered in all p atients on anticoagu lants
to closu re of the atriotom y w ith high p ressu re in the LV w ho have low card iac outpu t d ays to w eeks after the place-
(often perform ed by ad m inistering anterograd e card iople- m ent of a m itral valve. It is frequ ent in p atients w ho have
gia w ith retractors in p lace exposing the m itral valve, ren- becom e excessively anticoagu lated . Echocard iography is
d ering the aortic valve incom petent, thus filling the LV d iagnostic for this w ith great accu racy. The treatm ent is
w ith aortic p ressu re) w ill often reveal significant p ar- to reopen the incision and evacu ate the flu id collection,
avalvu lar leaks. These can be repaired w ith buttressing w hich shou ld result in immed iate improvement of p atients’
su tu res betw een the left atriu m and valve sew ing ring. hem od ynam ic stability. Directed need le asp iration or subx-
ip hoid p ericard ial d rain p lacem ent is also p ossible bu t m ay
Heart Block/Arrhythmias
not be su fficient if the blood is coagu lated .
Atrial fibrillation is associated w ith m itral valve d isease in
up to 50% of p atients (29). It is not uncom m on that these
patients develop atrial arrhythmias postoperatively. These ■ COMPLICATIONS OF MITRAL VALVE REPAIR
can often be treated acutely with -blockade and antiarrhyth-
mic agents such as amiodarone. Electrical cardioversion can
■ Residual mitral stenosis or regurgitation
be performed in the operating room or postoperatively if Mitral valve rep air techniqu es have evolved over the last
there is hem od ynam ic com p rom ise. d ecad es. At highly exp erienced centers, u p to 90% of
H eart block can occur w ith mitral valve surgery and is d egenerative/ m yxom atou s valves are able to be rep aired .
more common w ith MVR. Often this is d ue to ed ema near In p atients w ith MR, overaggressive leaflet resection or
the AV nod e as the sutures are placed near this structure d ow nsizing of an annu lop lasty ring can lead to m itral
and the heart block is often transient. Rarely, valve sutu res stenosis. Patients w ho p resent w ith m itral stenosis w here
are inad vertently placed throu gh the AV nod e, or the valve m itral valve rep air is attem p ted m ay have resid u al m itral
prosthesis compresses the nod e. When heart block persists stenosis. Diagnosis is m ad e in the op erating room by TEE,
for more than 7 d ays, a permanent pacemaker is consid ered . high left atrial p ressu re, and low card iac ou tp u t follow ing
rep air (31–33). In this setting, MVR shou ld be consid ered .
Postrep air MR after op eration for m itral stenosis is usually
■ Mechanical valve thrombosis the resu lt of an excessive com m issu rotom y. Significant MR
Throm bosis of a m echanical m itral valve can occu r late fol- is d etected by TEE. Usu ally, the incisions in the leaflet have
low ing MVR. The typical presentation is a low card iac ou t- m issed the fu sed com m issu res or a chord a su p p orting a
put refractory to all forms of su pport. Most patients rep ort section of the valve has been inad vertently cu t. The aorta
a recent p eriod w ith inad equate anticoagu lation. The m u st be clam p ed , card iop legia reinstitu ted , and the left
throm bosed m echanical p rosthesis has restricted leaflet atriu m reop ened . If the MR originates at the com m issu res,
motion on echocard iography. Since echocard iography can a p led geted stitch can correct this com p lication. If regurgi-
be lim ited w ith shad ow ing from the m echanical valve, tation p ersists, valve rep lacement is m and ated .
■ Persistent mitral regurgitation

Resid ual MR after operation for MR is probably the m ost
vexing of all p roblem s for the m itral repair surgeon. Resid -
ual MR alm ost alw ays resu lts from a lack of u nd erstand ing
of the exact geom etry of the u nd erlying p athology and an
inability to recreate a fu nctional intraventricu lar zone of
leaflet coap tation. Correction of this resid u al d eficit Prosthetic
requ ires a reconsid eration of the valve stru ctu re and either obstruction
re-rep air or rep lacem ent. The intraoperative TEE is p ara-
mount to und erstand ing the pathop hysiology of the leak-
ing m itral valve follow ing attem pted repair.
■ Left ventricular outflow tract obstruction

or abnormal systolic anterior motion
of the anterior leaflet
An often-mentioned complication of mitral valve repair is
FIGURE 28.4. Obstruction of the left ventricular outflow tract by a pros-
systolic anterior motion of the anterior leaflet. This occurs thetic mitral valve.
when too small an annuloplasty ring is placed during mitral
repair in patients with large mitral valves w ith excessive tis-
sue. This results in the coaptation point between the anterior annu loplasty sutures were not placed in the true annulus.
and posterior leaflets to be pushed anteriorly. The excessively The other potential mechanism is the use of too small an
large anterior leaflet then becomes w indsocked in the LV out- annuloplasty ring for the given annulus size. This puts excess
flow tract during systole resulting in an LV outflow track tension on the mitral annulus and results in ring dehiscence.
obstruction and significant residual MR. This problem can be Careful suture placement in the annulus and sizing of the
diagnosed by an increased left atrial pressure and reduced annuloplasty ring can help decrease this risk. When this
cardiac output; TEE can confirm the diagnosis. Often, this is a occurs, reoperation and repair of the dehiscence, re-repair of
dynamic finding and is associated w ith hypovolemia and the mitral valve, or replacement of the mitral valve is needed.
hypercontractility. Discontinuation of pressors and correc-
tion of intravascular volume deficit solve this in many cases.
Some authors advocate the use of -blockers. If these maneu- ■ COMPLICATIONS OF TRICUSPID
vers do not alleviate the obstruction, re-repair of the mitral VALVE SURGERY
valve consists of reducing the height of the posterior leaflet,
perhaps with a sliding valvuloplasty. As a last resort, MVR is
■ Right ventricular failure
possible. Similarly, a “tilted” placement of a prosthetic mitral The p rognosis and com p lications after TV op eration
valve can obstruct the LV outflow tract (Fig. 28.4). This gener- d ep end less on the valve su rgery itself than on the d u ra-
ally requires repositioning or replacement of the valve. tion of TV d isease, p articu larly tricu sp id regu rgitation
and RV hem od ynam ic abnorm alities. In one series, only
13% of p atients w ith chronic tricu sp id regu rgitation and
■ Hemolysis severe RV failu re had a good ou tcom e, w hereas 78% of the
Insertion of an annuloplasty mitral valve ring requires p atients w ho had no history of congestive heart failu re
sutu res placed around the annulus. If there is d ehiscence of and less RV d ysfu nction had a good ou tcom e (34). A
a su ture, the resu lt is a moving nonsupported ring that can recent stu d y su ggested that a MELD (m od el for end -stage
hem olyze red blood cells. H em olysis m ay occu r also in the liver d isease) score of 15 p red icts higher m ortality d u r-
absence of d ehiscence w hen a small jet of insignificant MR ing TV su rgery d u e to right heart d ysfu nction (35). The
hits a stitch or the ring itself. One m ay prod u ce either only a d ifficu lt p reop erative d ecision is w hether a p atient’s tri-
very minor d erangement or severe hemolysis w ith resulting cu sp id regu rgitation is the resu lt of TV d isease or is d u e to
anemia. -Blockad e, to red uce the force of the blood shear, p rim ary RV failu re. TV su rgery is likely to be cu rative in
and p entoxifylline, to make the red cells m ore “pliable,” the form er case bu t p ossibly lethal in the latter. Unfortu -
may be a satisfactory therapy. For some patients requiring nately, there are no com p letely reliable p reop erative
interm ittent transfu sion, reoperation is the only choice. m ethod s to p red ict recovery of RV systolic fu nction p ost-
op eratively. Sou nd clinical ju d gm ent based on a carefu l
Prosthetic Ring Dehiscence/Endocarditis exam ination of the p atient over tim e, along w ith the
Dehiscence of the prosthetic ring is often associated w ith resp onse to op tim al flu id and electrolyte m anagem ent,
end ocard itis and recu rrent MR. When this occu rs early fol- rem ains the best p reop erative ind icator. RV failu re has
low ing su rgery, the cau se is u su ally technical and the becom e m ore m anageable w ith the u se of vasod ilators;
p hosp hod iesterase inhibitors, su ch as m ilrinone; and (throu gh a m inithoracotom y on the left chest accessing the
inhaled nitric oxid e (36). LV apex d irectly).
With these techniqu es, a host of new com p lications
have been recognized . With the transfem oral ap p roach,
■ Rhythm disturbances vascu lar inju ry to the fem oral or iliac system is not u ncom -
The most common heart rhythm problem follow ing TV sur- m on as cu rren tly available valves requ ire a 18 to 26 F
gery is CH B. The risk of CH B is time-related ; the incid ence at sheath. With the transap ical ap p roach, bleed ing from the
5 weeks has been reported to be 5%, but it is 25% by 10 years. LV ap ex can be life threatening shou ld the rep air su tu res
The early risk is largely iatrogenic, having to do w ith suture not hold . With both ap p roaches, inap p rop riate p lacem ent
placement near the AV node, which is at the junction of the of the valve can resu lt in severe aortic insu fficiency, occlu -
anterior and septal leaflets of the TV (37). This can be mini- sion of the coronary arteries, or em bolization into the left
mized by jud icious placement of valve sutures, particularly ventricle. Coronary artery occlu sion m ay be treated w ith
near the triangle of Koch. Placing the sutures at the base of em ergent p ercu taneou s coronary intervention. If the
the valve leaflet rather than d eeper in the annulus ensures valve is p laced too high, it can som etim es be p u lled into
the greatest d istance from the cond uction system. The risk of the d escend ing aorta, left in p lace, and a new valve tran-
CH B is greater w hen tricuspid valve (TV) replacement or scatheter valve d ep loyed . Vascu lar com p lications can be
annuloplasty is combined w ith mitral valve proced ures than treated w ith covered stent grafts if recognized early.
after TV proced ures alone, because of sw elling on both sides Other com p lications su ch as em bolization of the valve
of the AV nod e or the bund le of H is. H eart block appears to into the left ventricle, severe aortic insu fficiency if the
occur less frequently after annuloplasty than after replace- valve is not p laced p rop erly, or aortic inju ry u su ally
ment of the TV—a d ifference of 6% versus 24% w as requ ire op en su rgical rep air.
observed in one series involving 47 patients. Late CH B is Inju ry to the AV nod e is not u ncom m on, and d epend ing
due to scar formation around the prosthetic valve annulus, on the typ e of valve inserted , u p to 25% of p atients m ay
particularly when a mitral or aortic prosthesis abuts it. CHB requ ire a p erm anent p acem aker w ith this ap p roach.
usually necessitates a permanent epicardial pacemaker sys-
tem for the patient. ■ REFERENCES
1. Bonow RO, Carabello B, d e Leon AC, et al. ACC/ AH A gu id elines for
the m anagem ent of p atients w ith valvu lar heart d isease: execu tive
■ Recurrent /residual tricuspid regurgitation sum m ary. J Heart Valve Dis 1998;7:672.
2. Carabello BA, Craw ford FA. Med ical p rogress: valvu lar heart d isease.
Comparative studies of recurrent/ residual tricuspid regurgi- N Engl J Med 1997;337:32.
tation after tricuspid annuloplasty are few. One prospective, 3. Rahim toola SH . Choice of p rosthetic heart valve for ad u lt p atients—
randomized study compared ring with stitch annuloplasty. review article. J Am Coll Cardiol 2003;41(6):893–904.
4. Chaitm an BR, Bonan R, Lep age G, et al. H em od ynam ic evalu ation of
At 64 months’ follow-up, there was a significantly greater the Carpentier-Ed w ard s porcine xenograft. Circulation 1979;60:1170.
incidence of moderate or severe postoperative tricuspid 5. Wernly JA, Craw ford MH . Choosing a p rosthetic heart valve. Cardiol
regurgitation in the DeVega stitch group (38). How ever, in Clin 1998;16:491.
6. Ed w ard s TJ, Livesey SA, Sim p son IA, et al. Biological valves beyond
both grou p s, control of tricu sp id regu rgitation w as p oor, fifteen years: the Wessex exp erience. Ann Thorac Surg 1995;60:S211.
particularly w ith elevated pulmonary vascular resistance or 7. Bernal JM, Rabasa JM, Lop ez R, et al. Du rability of the Carp entier-
organic TV disease. Although long-term survival was termed Ed w ard s p orcine bioprosthesis: role of age and valve p osition. Ann
Thorac Surg 1995;60:S248.
excellent, recurrence of at least mod erate tricuspid regurgita- 8. Doty JR, Flores JH , Millar RC, et al. Aortic valve rep lacem ent w ith
tion occurs in many patients; most do not require reopera- Med tronic freestyle biop rosthesis: op erative techniqu e and resu lts.
tion. A very recent study advocated an aggressive approach J Card Surg 1998;13:208.
9. Akins CW. Resu lts w ith m echanical card iac valvu lar p rostheses. Ann
of TV annuloplasty, even with minor tricuspid regurgitation, Thorac Surg 1995;60:1836.
if the annulus w as dilated. This study showed infrequent 10. H am m erm eister KE, H end erson WG, Bu rchfiel CM, et al. Com p arison
recurrent tricuspid regurgitation in the group treated w ith of ou tcom e after valve rep lacem ent w ith a biop rosthesis versu s a
m echanical p rosthesis: initial 5 year resu lts of a rand om ized trial. J Am
annuloplasty for less severe d ilation (39). Coll Cardiol 1987;10:719.
11. Steu sse DC, Vlessis AA. Ep id em iology of native valve end ocard itis. In:
Vlessis AA, Bolling SF, ed s. Endocarditis: a multidisciplinary approach.
■ COMPLICATIONS OF TRANSCATHETER Arm onk, N Y: Fu tu ra, 1999:77.
12. Vlessis AA, H ovaguim ian H , Jaggers J, et al. Infective end ocard itis: ten-
AORTIC VALVE REPLACEMENT year review of m ed ical and su rgical therapy. Ann Thorac Surg 1996;
61:1217.
N ovel m ethod s to replace the aortic valve w ithout the need 13. Schw artz CF, Bolling SF. Mitral valve end ocard itis. In: Vlessis AA,
for sternotom y, arrest of the heart or even card iopulm onary Bolling SF, ed s. Endocarditis: a multidisciplinary approach. Arm onk, N Y:
Fu tu ra; 1999:263.
bypass are w id ely available in Europe and available in the 14. H u sebye DG, Pluth JR, Piehler JM, et al. Reop eration on p rosthetic
United States in trials. With these techniques, the native heart valves: an analysis of risk factors in 552 p atients. J Thorac Cardio-
aortic valve is ballooned open bu t not rem oved . A stented vasc Surg 1983;86:543–552.
15. Lytle BW, Cosgrove DM, Taylor PC, et al. Reop eration for valve su r-
valve is p laced in the aortic annu lu s either throu gh a trans- gery: periop erative m ortality and d eterm inants of risk for 1,000
fem oral artery approach or through a transapical app roach p atients. Ann Thorac Surg 1986;42:632–643.
16. Teoh KH , Ivanov J, Weisel RD, et al. Su rvival and biop rosthetic valve 28. Fenster MS, Feld m an MD. Mitral regu rgitation: an overview. Curr Probl
failu re. Circulation 1989;80(Su p p l 1):8–15. Cardiol 1995;20:193.
17. David TE, Bos J, Christakis GT, et al. H eart valve op erations in p atients 29. Ailaw adi G, Swenson BR, Girotti ME, et al. Is mitral valve repair supe-
w ith active infective end ocard itis. Ann Thorac Surg 1990;49:701. rior to replacement in elderly patients? Ann Thorac Surg 2008;86(1):77–85.
18. Lind blom D. Long-term clinical resu lts after aortic valve rep lacem ent 30. Solom on H , Lim DS, Ragosta M. Percu taneou s ventricu lar assist d evice
w ith the Bjork-Shiley p rosthesis. J Thorac Cardiovasc Surg 1988;95: to rescu e a p atient w ith p rofou nd shock from a throm bosed p rosthetic
658–667. m itral valve. J Invasive Cardiol 2008;20(11):E320–E323.
19. Lap ar DJ, Ailaw ad i G, Bham id ip ati CM, et al. Use of a nonp led geted 31. David TE, Ud en DE, Strau ss H D. The im p ortance of the m itral ap p ara-
su tu re techniqu e is safe and efficient for aortic valve rep lacem ent tus in left ventricu lar function after correction of m itral regu rgitation.
[p u blished online ahead of p rint May 18, 2010]. J Thorac Cardiovasc Circulation 1983;68:II76.
Surg. 2011;141(2):388–393. 32. Akins CW, H ilgenberg AD, Bu ckley MJ, et al. Mitral valve reconstru c-
20. Kalu s JS, White CM, Caron MF, et al. Ind icators of atrial fibrillation risk tion versus replacem ent for d egenerative or ischem ic m itral regurgita-
in card iac su rgery p atients on p rop hylactic am iod arone. Ann Thorac tion. Ann Thorac Surg 1994;58:668.
Surg 2004;77(4):1288–1292. 33. Roberts WC, McIntosh CL, Wallace RB. Mechanism s of severe m itral
21. Kobayashi J, Kosakai Y, Isobe F, et al. Rationale of the Cox m aze p roce- regurgitation in m itral valve prolapse d eterm ined from analysis of
d u re for atrial fibrillation d u ring red o m itral valve op erations. J Thorac operatively excised valves. Am Heart J 1987;113:1316.
Cardiovasc Surg 1996;112:1216. 34. Bernal JM, Gutiérrez-Morlote J, Llorca J, et al. Tricuspid valve repair: an
22. Carr JA, Savage EB. Aortic valve rep air for aortic insufficiency in old disease, a mod ern experience. Ann Thorac Surg 2004;78(6):2069–2074.
ad u lts: a contem p orary review and com p arison w ith rep lacem ent tech- 35. Ailaw ad i G, Lap ar DJ, Sw enson BR, et al. Mod el for end -stage liver d is-
niqu es—review article. Eur J Cardiothorac Surg 2004;25(1):6–15. ease p red icts m ortality for tricu sp id valve su rgery. Ann Thorac Surg
23. David TE, Kom ed a M, Brofm an PR. Su rgical treatm ent of aortic root 2009;87(5):1460–1467.
abscess. Circulation 1989;80(Su p p l 1):269–274. 36. Thorbu rn CW, Morgan JJ, Shanahan MX, et al. Long-term resu lts of tri-
24. Magovern JA, Pennock JL, Cam p bell DB, et al. Aortic valve replace- cu spid valve replacem ent and the problem of prosthetic valve throm -
m ent and com bined aortic valve replacem ent and coronary artery bosis. Am J Cardiol 1983;51:1128–1132.
bypass grafting: pred icting high risk grou p s. J Am Coll Cardiol 1987;9: 37. Breyer RH , McClenathan JH , Michaelis LL, et al. Tricu spid regurgita-
38–43. tion: a com parison of nonop erative m anagem ent, tricu sp id annu lo-
25. N ajafi H , Dye WS, Javid H , et al. Mitral valve rep lacem ent: review p lasty and tricu spid valve replacem ent. J Thorac Cardiovasc Surg 1976;72:
of seven years’ exp erience—review article. Am J Cardiol 1969;24(3): 867–874.
386–392. 38. Peterffy A, Jonasson R, H enze A. H aem od ynam ic changes after tricu s-
26. Bu ceriu s J, Gu m m ert JF, Borger MA, et al. Stroke after card iac surgery: p id valve su rgery: a recatheterization stu d y in forty-five p atients. Scand
a risk factor analysis of 16,184 consecu tive ad u lt p atients. Ann Thorac J Thorac Cardiovasc Surg 1981;15:161–170.
Surg 2003;75(2):472–478. 39. Dreyfus GD, Corbi PJ, John Chan KM, et al. Second ary tricu sp id regu r-
27. Jennifer C, O’Brien B, Schneck M. Risk of stroke follow ing valve gitation or d ilatation: w hich shou ld be the criteria for su rgical rep air?
rep lacem ent su rgery. Semin Cerebrovasc Dis Stroke 2003;3(4):214–218. Ann Thorac Surg 2005;79(1):127–132.
CHAPTER
29
Complications of Thoracoscopy
J ames M. Donahue, Michael A. Smith, and Richard J . Battafarano
■ BACKGROUND ability to control vital stru ctu res in the event of emergent
blood loss, and the high cost of sp ecialized equ ip m ent.
The use of end oscopy for diagnostic and therapeutic proce- In ad d ition , th ere are contraind ications to thoracoscop y
dures of the chest w as introd uced in 1910 by the Sw ed ish (Table 29.2) that also d iminish the p rosp ect of using this
physician Hans Christian Jacobaeus (1). Over the follow ing approach in certain patients. The technical accomplishment
decad es thoracoscopy developed into a routine proced ure of VATS proced ures requires certain cond itions in ord er to
for the d iagnosis and management of pleural space com pli- be safe and effective. The most important requirement is that
cations of tuberculosis. As antimicrobial therapy for tubercu- the surgeon be able to see the operative field . Therefore, tw o
losis developed, the use of thoracoscopy waned. Not until absolute contraind ications to VATS are a fused pleural space
the 1990s, w ith the rapid ad option of m inimally invasive from prior surgery or inflammation and an inability to toler-
laparoscopic techniques, d id thoracoscopy become more ate single lung ventilation second ary to preexisting lung dis-
w id ely utilized . Tod ay, vid eo-assisted thoracic surgery ease or cardiopulmonary instability. In general, resection of
(VATS) refers to a m inimally invasive approach to chest sur- tumors 4 cm in diameter is also a contraindication for a
gery that avoid s rib spreading and requires visualization by VATS approach. Relative contraind ications include endo-
video technology. Currently, VATS is the stand ard approach bronchial tumors seen on bronchoscopy, obesity, coagulopa-
for many d iagnostic and therapeutic proced ures involving thy, extensive hilar lymphad enopathy, prior hilar rad iation,
the lung, pleura, esophagus, and med iastinum (Table 29.1). and chest wall involvement. It is important for surgeons to
In some w ays, the minimally invasive nature of this understand the potential complications associated with the
approach has changed the way in w hich patients are man- thoracoscopic approach in ord er to id entify the patients
aged . This is particularly true for biopsies of peripheral pul- most likely to benefit from this m inimally invasive tech-
monary nod ules and d ensities, w hich, historically, have nique. If there are no absolute contraind ications, many sur-
been followed with serial imaging studies. geons w ill begin w ith the VATS technique and w ill convert
When considering w hether to proceed with a VATS to open thoracotomy if they are unable to proceed safely.
approach for a given d iagnostic or therapeutic proced ure, it
is important to consid er the advantages and disadvantages
as w ell as contraind ications for each individual patient.
VATS is often preferable to open procedures because it
■ RISK ASSESSMENT
reduces surgical trauma, decreases pain and postoperative In an effort to avoid com plications in the intraoperative
narcotic use, and preserves pulmonary function (2). These and p ostop erative p eriod s, a p reop erative risk assessm ent
factors may allow old er patients or patients w ith significant m u st be p erformed . Many algorithm s have been d eveloped
med ical comorbid ities w ho are poor cand id ates for thoraco- to system atically stratify the risk of cand id ates for chest
tomy to und ergo d iagnostic or therapeutic interventions (3). su rgery based u p on p reop erative d ata su ch as age, exercise
The appeal of the VATS approach for diagnostic proced ures cap acity, sp irom etric valu es, and m easu res of gas exchange
is well-recognized in the thoracic community. More recently, and d iffu sing cap acity. N o single factor has been proven as
the use of VATS has become increasingly popular for major being p red ictive for the d evelop m ent of com p lications. In
anatomic pulmonary resections. Accord ing to a recent analy- an effort to im p rove p red ictive ability, variou s factors have
sis of the Society of Thoracic Surgery (STS) database, 32% of been accou nted for in scoring system s. The Card iopu l-
all lobectomies were performed using VATS in 2006 (4). m onary Risk Ind ex (CPRI) and the Physiological and Op er-
The d isad vantages of VATS includ e a fairly steep learn- ative Severity Score for the Enu m eration of Mortality and
ing curve, the loss of tactile sensation, poor access to and Morbid ity (POSSUM) are general scoring system s that
have been u sed for lu ng resection w ith variable p red ictive
James M. Donahue, Richard J. Battafarano: Division of Gen- ability (5–7). Ad d itional scoring system s sp ecifically d evel-
eral Thoracic Surgery, University of Maryland , Baltimore, MD. op ed for lu ng resection, su ch as the Pred ictive Resp iratory
Michael A. Smith: Division of General Thoracic Su rgery, Qu otient (PRQ) (8) and the Pred icted Postop erative Prod -
Saint Josep h's H osp ital and Med ical Center, Phoenix, AZ. u ct (9), have not gained w id esp read u se.
320
Chapter 29 • Complications of Thoracoscopy 321
Table 2 9 .1 M in im a lly in va sive p roced u r es tions u sing a VATS ap p roach (10,11). H ow ever, their risks
of t h e ch est are still su bstantial w hen com p ared to the general pop ula-
tion and shou ld not be u nd erestim ated . Another consid era-
Pulmonary tion specific to VATS is the clinical stage and location of
Wedge resection d isease. Central lu ng lesions are m ore d ifficu lt to d eal w ith
Lobectomy than peripheral lesions from both a d iagnostic and thera-
Pneumonectomy p eu tic stand p oint. The close p roxim ity of central lu ng
Esophageal lesions to m ajor p u lm onary vessels can increase the risk of
Fundoplication ap p roaching these u sing a VATS ap p roach (12). For this
Myotomy reason it is im portant to set size and location criteria for
Leiomyoma resection VATS ap p roaches to lu ng lesions. Disregard ing these crite-
Esophagectomy
ria w ill m ake the p atient vu lnerable to com p lications.
Cardiac
Pericardial window
Nervous System
■ GENERAL COMPLICATIONS
Sympathectomy Although the VATS app roach m ay be less trau m atic than
Other thoracotom y, the anatom ic and p hysiologic consequences
Thymectomy of the op eration rem ain the sam e. Therefore, all p otential
Mediastinal mass excision com p lications that m ay be associated w ith the op en p ro-
ced u re m ay also be encou ntered in the sam e op eration
p erform ed by VATS. H ow ever, there are intraoperative
Most su rgeons d o not rely com p letely on a p articu lar com p lications that are sp ecific to VATS. In early stu d ies
scoring system to d eterm ine a p atient’s su rgical fitness. exam ining the safety of VATS for nonanatom ic d iagnostic
H ow ever, m any of the factors that make up these scoring and therap eu tic resections, m ortality rates ranged from
system s, along w ith surgical ju d gm ent, are u sed to make 0.5% to 2.5%, w hile m orbid ity rates varied from 4% to 14%
the u ltim ate d ecision. Som e of these factors inclu d e p atient (10,13–15). Recent large review s from ind ivid u al institu-
age, p u lm onary fu nction, clinical stage of d isease, and the tions of excellence exam ining the use of VATS for m ajor
presence of com orbid illnesses. Patients w ho w ou ld nor- anatom ic resections rep ort m ortality rates from 0.7% to
m ally be consid ered high risk becau se of ad vanced age, 1.2% and morbid ity rates from 15% to 26% (16–18). A recent
poor p u lm onary fu nction, and low fu nctional statu s m ay report from the Am erican College of Su rgeons Oncology
actually exp erience better outcom es w ith few er com p lica- Group d etails the m orbid ity and m ortality follow ing m ajor
p ulmonary resections in p atients w ith early-stage lu ng can-
cer in the Z0030 trial. This p rosp ective, rand om ized trial
Table 2 9 .2 Con t r a in d ica t ion s t o t h or a coscopy w as d esigned to com pare lym p h nod e sam pling versu s
m ed iastinal lym p h nod e d issection in early-stage lu ng can-
Absolute
cer. Becau se 94% of p atients in this stu d y u nd erw ent thora-
Fused pleural space
cotom y, it serves as an excellent m od ern benchm ark by
Prior thoracotomy
Severe inflammatory process w hich to assess resu lts follow ing thoracotom y. In this
Prior pleurodesis stu d y, m ortality w as 1.4%, and m orbid ity w as 38% (19).
Finally, an analysis of the STS d atabase u sing propensity
Inability to tolerate single lung ventilation
m atching to com p are a VATS ap p roach versu s thoraco-
Prior pneumonectomy
Severe respiratory failure tom y for patients u nd ergoing lobectom y reported m ortal-
ity rates of 0.94% in the VATS grou p and 1.01% in the
Hemodynamically unstable patient
thoracotom y grou p . Overall m orbid ity rates w ere 26.2% in
Cardiac arrest
the VATS grou p and 34.7% in the thoracotom y group (20).
Severe trauma
Relative
High risk of incomplete resection or dissemination ■ INTRAOPERATIVE COMPLICATIONS
Tumor 4 cm
The initial reservation w ith m inim ally invasive su rgery in
Central pulmonary lesions
Endobronchial tumor the chest w as a concern for safety. H ow ever, over the
Hilar lymphadenopathy years, it has been show n that m inim ally invasive chest su r-
gery can be p erform ed for a variety of p roced u res w ith
Prior hilar radiation
safety that is com p arable to op en thoracotom y. To a great
Chest wall involvement d egree, safety d ep end s on good su rgical ju d gm ent for con-
Coagulopathy version to op en thoracotom y for technical reasons or w hen
Obesity an op en op eration is m ore ap p rop riate. The m ost com m on,
im m ed iately life-threatening intraop erative com p lications
of chest su rgery are m assive hem orrhage, card iogenic d is- d u ring anatom ic VATS resections is the failu re to correctly
tu rbances, and ventilatory p roblem s. recognize vascu lar or bronchial stru ctu res. Du ring open
lobectom y, the m ost com m on ap p roach involves opening
the fissures to obtain control of the pulmonary arterial
■ Hemorrhage branches. This approach is generally not performed during
Massive intraoperative hemorrhage is the most w orrisome the performance of a VATS lobectomy. In the VATS approach,
complication for surgeons w hen consid ering minimally u p p er lobectomies are generally p erform ed by p roceed ing
invasive p roced u res in the chest becau se of the d ifficu lty in w ith the hilar d issection from anterior to p osterior, w hile
obtaining central control of the pulmonary artery and veins low er lobectom ies are usually perform ed from inferior to
using the VATS techniqu e. Massive hemorrhage in the chest su p erior. This m ay be confu sing d u ring the initial experi-
can result from great vessel injury or, more commonly, ence w ith the techniqu e. It is essential to correctly id entify
inju ry to a pulm onary artery or vein branch su stained d ur- stru ctu res p rior to d ivid ing them . This often requ ires m ov-
ing pu lm onary d issection. The pu lm onary artery and its ing the cam era to d ifferent port sites in ord er to exam ine
branches are particularly thin-w alled and easily inju red critical stru ctu res from d ifferent angles.
d uring manipulation or traction employed to increase expo-
sure. In contrast, the w alls of the pulmonary vein are m ore
resilient and w ithstand surgical manipulation much better.
■ Intraoperative cardiogenic disturbances
The risk of a d ifficult d issection and pulmonary artery As m en tion ed p reviou sly, ad equ ate visu alization is
inju ry can be anticipated in p atients w ho have had ind uc- extrem ely im p ortant w hen u sin g a VATS ap p roach . The
tion chemotherapy or prior irrad iation. In ad d ition, patients insu fflation of CO 2 aid s in the com p ression of lu ng
w ith med iastinal granulomatosis or prior silica exposure p arenchym a and the effacem ent of su bp leu ral lesions, and
w ill have regional bronchopulmonary lymph nod es d ensely it acts as a retractor w hen com bined w ith changes in the
ad herent to branch p ulmonary arteries. In su ch cases, it is p atient’s p osition. Initially, there w as relu ctance to u sing
prud ent to begin the su rgical d issection by encircling the CO 2 insufflation becau se of concern over hem od ynam ic
ipsilateral m ain pu lm onary artery and both pu lm onary com prom ise. Intrap leu ral CO 2 insu fflation has been show n
veins so as to have proximal and d istal control in the event to have ad verse hem od ynam ic consequences in laboratory
of vessel inju ry. Another reported cause of major intraoper- anim al stu d ies (23). H ow ever, in the clinical setting, low -
ative bleed ing is the mechanical failure of vascu lar staplers, p ressu re ( 10 m m H g) insu fflation of CO 2 d u ring thora-
althou gh this is rare (21,22). Some authors recomm end the coscop y is safe and w ithou t significant hem od ynam ic
central placement of vascular clamps prior to vessel d ivi- consequ ences excep t for an elevation of central venou s
sion to minimize the sequelae of misfiring staplers. p ressu re (15). The p ressu res and flow rates shou ld be kept
Because the pulmonary circulation is a low -pressure, at 10 m m H g and 2 L/ m in, resp ectively, to avoid signifi-
high-flow system, arterial and venous injury can almost cant central venou s p ressu res or rap id m ed iastinal m ove-
alw ays be immed iately controlled with local pressure at the m ent. In ad d ition, intrap leu ral CO 2 insu fflation shou ld be
injury site. After local control of the bleeding is obtained, the initiated only if there are no significant ad hesions p resent
surgeon, know ing the injury’s site and magnitud e, must to prevent p leu ral and parenchym al inju ry.
make an immed iate d ecision on w hat w ill be required to Patients w ith preexisting heart d isease are at risk for
control the bleed ing. In the setting of VATS, the operative m ore typ ical intraop erative card iogenic d istu rbances su ch
view can be lost very quickly. Therefore, attempts to place a as ischem ia and arrhythmias. It is im p ortant to id entify
vascular clamp to control bleeding should be avoided . In the these p atients from their m ed ical history, p hysical exam ,
case of a pulmonary artery injury, this may, in fact, exacer- and p reop erative testing to d eterm ine the need for preop-
bate the injury. A better alternative to controlling bleed ing erative p rop hylactic m easu res to avoid card iac ischem ia
during VATS is to gain immediate control with a gentle and to select those w ho need intraop erative Sw an–Ganz
application of pressure using a sponge-stick through the catheter m onitoring. Of p articu lar note, for p atients w ho
utility incision or a port site. This will give ample time to have u nd ergone p reviou s CABG u sing a left internal m am -
gain better exposure w ith an open incision and to repair the m ary artery graft, sp ecial care m u st be taken w hen per-
injury if needed. Rarely will an injury to the main pul- form ing p roced u res on the left u p p er lobe so as not to
monary artery, the left atrium med ial to the pulmonary vein, d am age the graft. Patients w ithou t p reexisting card iac d ys-
or the superior or inferior vena cava require a card iopul- fu nction can also d evelop intraop erative arrhythm ias d u e
monary bypass to control the situation for ad equate repair. to hyp otherm ia, hyp oxemia, hyp okalem ia, hyp erkalem ia,
In ad d ition, inju ries to bronchial arteries, parenchym al hyp ovolem ia, or acid osis. When they occu r, these p roblem s
surfaces, and p leu ral ad hesions, as w ell as intercostal and m u st be corrected as soon as p ossible. Electrical card iover-
internal m am m ary vessels can also lead to significant intra- sion m ay be necessary in the case of hem od ynam ically sig-
operative blood loss if they go unnoticed . It is im portant to nificant arrhythmias. H ow ever, the arrhythm ia m ay be
use carefu l d issection techniqu es at all tim es d u ring the recalcitrant to electrical card ioversion if the und erlying d is-
op eration to avoid inju ries to these stru ctu res and to con- tu rbance is not corrected (i.e., hyp otherm ia, hyp erkalem ia).
trol them qu ickly w hen they occur. A particu lar concern In ad d ition, m anip u lation and com p ression of the heart for
exposu re can also lead to arrhythm ias and ischem ia. Often, exams, and routine chest X-rays, in addition to having a high
these m aneu vers cannot be com pletely avoid ed , bu t they index of suspicion during the postoperative period will help
mu st be lim ited in d u ration and frequency, u sing close the clinician to identify complications and manage them effec-
com m unication betw een the surgeon and anesthesiologist tively. Recent outcome analyses of large series of anatomic
to help id entify the effects on blood p ressu re and rhythm . VATS resections provide insights into the post-operative com-
plications of these procedures when compared to resections
performed via thoracotomy. When interpreting these results,
■ Ventilatory complications it must be kept in mind that patients in these nonrandomized
A host of ventilatory problems can put the patient’s gas studies are highly selected and may not represent the general
exchange and hemod ynamic stability at risk. As ventilation patient population. In this section, we will examine the results
is established through either a d ou ble lum en end obronchial and management strategies for three of the most common
tube or a single lumen tube w ith a bronchial blocking bal- postoperative complications: prolonged air leaks, pneumo-
loon, it is essential for the anesthesiologist, as w ell as the nia, and atrial fibrillation. Many thoracic surgical investiga-
surgeon, to be confid ent that proper positioning has been tors are interested in the differences in the incidence of these
established p rior to starting the resection. The su rgeon m u st complications between open and VATS approaches.
also be aw are of the presentation of tu be d isplacement.
H igh airw ay pressu re and absent CO 2 in the ventilator cir- ■ Residual air space and prolonged air leaks
cuit ind icate that the bronchial cuff or bronchial blocking
balloon has herniated into the trachea, causing tracheal During the norm al cond u ct of VATS or open pu lm onary
obstru ction. Deflation of the cuff or balloon solves the prob- resections, there can be small inju ries to the visceral pleura,
lem and ad vancement of the tube or balloon prevents the resu lting in air leaks. These sm all visceral pleu ral injuries
problem from reoccurring. While cond ucting a right-sid ed can be minimized w ith meticu lous techniqu e. N ormally,
resection w ith ventilation only on the left, persistent hypox- these sm all air leaks resolve w ith the ap position of p leural
emia suggests that the balloon on the left limb of the d ouble surfaces once the lung is reexpand ed . A resid u al air space
lumen tube has ad vanced too far and has occlud ed the left exists w hen there is a failure in filling the chest cavity after
upper lobe orifice. This problem is sometimes first d etected the reexpansion of the lu ng. Greater am ounts of parenchy-
by the attentive surgeon, w ho recognizes that the m ed i- mal resection increase the risk of resid ual air space. Thus,
astinu m’s u su al ventilatory movement is absent becau se of bilobectom ies and lobectomies have higher rates of resid ual
the p rogressive atelectasis of the left u pper lobe. Rep osition- air space than segmentectomies and w ed ge resections. Usu-
ing the tube solves the problem. Communication betw een ally the space is noted at the apex after up per lobectomy
the su rgeon and anesthesiologist is critical for the su ccessful and at the base near the d iap hragm after low er lobectom y.
completion of VATS proced ures. Early recognition of a In m any p atients, resid u al air sp ace in the absence of a
patient not tolerating single lung ventilation is of critical p ersistent air leak w ill not be associated w ith any signifi-
importance to avoid having to inflate the lung on the opera- cant m orbid ity. The sp ace grad u ally d isap p ears over sev-
tive sid e im m ed iately. This could prove d isastrous if it coin- eral w eeks, second ary to the reabsorp tion of gases w ithin
cid es w ith a critical portion of the hilar dissection and could the sp ace, fu rther reexp ansion of the lu ng, shift of the
lead to significant bleed ing. m ed iastinu m to the op erative sid e, and elevation of the
Patients u nd ergoing lu ng su rgery are more su sceptible ip silateral hemid iaphragm. When a resid ual air space is
to pneu m othorax second ary to barotraum a becau se of pre- associated w ith symptoms su ch as pain, d yspnea, hemopty-
existing emphysema from smoking. Pneumothorax can sis, or fever, a bronchop leu ral fistu la w ith empyema should
occur at the time of ind u ction and at the onset of positive be su spected and requires appropriate intervention w ith
pressure ventilation or at any point d uring the actu al op era- thoracostom y tube placem ent and possible reoperation.
tion on the contralateral sid e. The surgeon should be aw are As w ith op en lu ng resection, p rolonged air leak is the
of this d evelopment since airw ay p ressu res w ill increase, m ost com m on cau se of morbid ity and p rolonged hosp ital
and the rhythmic movement of the med iastinum w ill be stay after VATS lu ng resection. It also increases patient d is-
absent. Ind eed , the med iastinu m w ill sometimes balloon com fort, cost of care, and the u tilization of resources. Pro-
out tow ard the operative sid e, causing an obstru ction of the longed air leak is resp onsible for ap p roxim ately 25% of all
venous retu rn and hem od ynam ic comprom ise. Opening m orbid ity after lu ng resection. An air leak that persists for
the m ed iastinal pleu ra easily rem ed ies the problem . m ore than 5 to 7 d ays after su rgery is generally consid ered
a p rolonged air leak. As d ep icted in Table 29.3, the occur-
rence of a prolonged air leak after VATS lobectom y in the
■ POSTOPERATIVE COMPLICATIONS Ced ars Sinai series w as 5.1%. In the ACOSOG Z0030 trial,
the incid ence of p rolonged air leak after op en resection
■ General considerations w as 7.6%. The incid ence of p rolonged air leak in other
Several complications can arise after chest surgery. Many can large VATS series ranges from 4% to 7.7% (17,18). In the
be fatal if not recognized and managed early and aggressively. p rop ensity-m atched analysis of the STS d atabase d ep icted
Paying attention to the details of patient symptoms, clinical in Table 29.4, p rolonged air leak occu rred in 7.6% of
Table 2 9 .3 VATS ver su s t h ora cot om y: m or bid it y lu ng volu m e red u ction su rgery (24). H ow ever, their effi-
a n d m or t a lit y com p a r ison fr om la r ge cacy for comp leting fissu res d u ring lobectom y and seg-
ser ies of a n a t om ic r esect ion s m entectom y is u nclear. Previou sly, Venu ta et al. (25) fou nd
that the u se of p ericard ial strip s to com p lete interlobar fis-
Thoracotomy su res for p u lm onary lobectom y significantly red u ced the
VATS (Cedars Sinai) (ACOSOG Z0030) d u ration of p ostop erative air leaks and hosp ital stay. The
Patients 1,100 1,023 u se of p ericard ial bu ttressing strip s has been d escribed in
Mortality 0.8 1.4 conju nction w ith the VATS ap p roach (26) and has been
show n to low er the p rolonged air leak rate after VATS lu ng
Reoperation for bleeding 0 1.5
volu m e red u ction su rgery (27,28).
Prolonged air leak 5.1 7.6 Other m easu res to red u ce the incid ence of p rolonged
Empyema 0.4 1.1 air leaks in high-risk p atients are m aneu vers that d isplace
Pneumonia 1.2 2.5 the p otential resid u al sp ace to an extrap leu ral p osition,
thereby m aking the ap p osition of p leu ral su rfaces m ore
Bronchopleural fistula 0.3 0.5
likely. One com m on p ractice is the creation of a pleu ral
Atelectasis 0.2 6.4 tent. In a p rosp ective rand om ized stu d y of 200 patients
ARDS 0.1 0.7 u nd ergoing u p p er lobectom y (29), it w as fou nd that pleu -
Atrial fibrillation 2.9 14.4 ral tenting red u ced the d u ration of air leaks and hosp ital
costs. Sim ilarly, other rand om ized and retrosp ective stud -
ARDS, adult respiratory distress syndrome; VATS, video-assisted thoracic surgery. ies (30,31) show ed that p leu ral tenting follow ing lobec-
tom y shortens the d u ration of chest tu be d rainage and
hosp ital costs. The u se of p leu ral tents has also been
patients after VATS lobectom y versu s 8.7% of patients in d escribed w ith the VATS ap p roach (25). A second w ay to
the op en lobectom y grou p (p N S). lim it the potential resid u al p leu ral air space is to elevate the
The m ost consistent risk factor for p rolonged air leak d iap hragm by insu fflating air into the p eritoneal cavity.
after anatom ic resection is severe obstru ctive pulm onary Pneu m op eritoneu m has been d escribed to treat air leaks
d isease. Other p otential risk factors for p rolonged air leak and resid u al sp aces after lu ng volu m e red u ction su rgery
includ e ad vanced age, p leu ral ad hesions, preoperative (32). Su bsequ ently, De Giacom o et al. (33) d escribed its u se
steroid u se, and ind u ction chem o/ rad iation therap y. Pre- after p u lm onary resection. In a p rosp ective rand om ized
op erative aw areness of increased risk for p rolonged air stu d y of 16 p atients u nd ergoing bilobectom y, Cerfolio et al.
leaks shou ld engend er extra m easu res in ad d ition to m etic- show ed that intraop erative creation of p neu m op eritoneu m
ulous techniqu e d u ring the operation to help prevent them . d ecreased the incid ence of air leaks and shortened hosp ital
The u se of bovine p ericard ial strip s as a bu ttress along the stay w ithou t increasing m orbid ity (34).
lung staple line to d ecrease air leaks w as first d escribed for A third m easu re that has been used for p rolonged air
leak is the u se of biologic sealants. Prior rep orts have
show n (35,36) that fibrin glu e is not effective in red ucing
Table 2 9 .4 VATS ver su s t h ora cot om y: m or bid it y the d u ration of air leaks after lobectomy. H ow ever, Fabian
a n d m or t a lit y com p a r ison in et al. (37) show ed in a rand om ized stu d y that fibrin glue
p rop en sit y-m a t ch ed a n a lysis of red u ced the rate of p ostop erative air leak from 15% to 2%
p a t ien t s u n d er goin g lobect om y after lu ng resection. Sim ilarly, Wain et al. (38) fou nd that
in STS d a t a ba se fibrin glu e–treated p atien ts h ad a m ean air leak tim e of
31 hou rs w hile u ntreated p atients had a m ean air leak tim e
VATS Thoracotomy p-value of 52 hou rs. Althou gh this d ifference w as significant, there
Patients 1,281 1,281 – w as no red u ced tim e for chest tu be rem oval or earlier hos-
Mortality 0.9 1.0 NS p ital d ischarge. Becau se thoracoscop ic p roced u res w ere
exclu d ed from both of these sealant trials, fu rther stu d y is
Reoperation for bleeding 1.3 0.6 NS
need ed to d eterm ine efficacy, p atient selection, and the cost
Prolonged air leak 7.6 8.7 NS effectiveness of fibrin sealants for preventing prolonged air
Pneumonia 3.0 4.4 NS leak for VATS pu lm onary resection.
Bronchopleural fistula 0.2 0.2 NS Desp ite p reventive m easu res, m any p atients go on to
d evelop p rolonged air leak. Althou gh this is the m ost com -
Atelectasis 2.1 3.3 NS
m on p roblem thoracic su rgeons d eal w ith in the p ostop era-
ARDS 0.7 0.8 NS tive p eriod , there is no consensu s on its m anagem ent. Most
Reintubation 1.4 3.1 0.0046 su rgeons believe that conversion from su ction to w ater seal
Atrial fibrillation 7.3 11.5 0.0004 is an effective w ay of encou raging an air leak to seal. Devel-
op m ent of a p neu m othorax in the setting of an exp iratory
ARDS, adult respiratory distress syndrome; VATS, video-assisted thoracic surgery. air leak is u ncom mon. This is su p p orted by a stu d y by
Cerfolio et al. (39) in w hich 33 patients w ith postop erative the Z0030 trial, the incid ence of p neu m onia after op en
air leak w ere rand om ized to continu ed suction versu s resection w as 2.5%. The incid ence of p neu m onia in the
w ater seal on p ostoperative d ay 2. They fou nd that 67% of Du ke VATS series w as 5% (17). Becau se p neu m onia is a
the p atients treated w ith w ater seal had air leak resolu tion clinical d iagnosis, other measu res of sp u tu m retention and
by p ostop erative d ay 3 versu s 7% of the p atients w ho p oor airw ay hygiene m u st be analyzed in ord er to m ore
rem ained on su ction. Air leaks that d o not resolve on w ater com p letely gau ge its p revalence. As m entioned above,
seal shou ld be p laced on a H eim lich valve once the flu id m any p atients w ith significant sp u tu m retention u ltim ately
d rainage is m inim al. The patient can be d ischarged w ith requ ire bronchoscop y for atelectasis. In the Ced ars Sinai
the chest tu be and H eim lich valve in p lace as long as there series, only 0.2% of p atients w ere rep orted as experiencing
is no new or enlarging pneum othorax apparent on the atelectasis, w hile 6.4% of p atients in the Z0030 trial had
chest X-ray. Ou tpatient chest tube m anagem ent is w ell- atelectasis. In the p rop ensity-matched analysis of the STS
tolerated and d esirable for the p atient since it avoid s p ro- d atabase d ep icted in Table 29.4, p neu m onia occurred in
longed hosp italization. Most air leaks stop after several 3.0% of p atients after VATS lobectom y versus 4.4% of
d ays, and the chest tu be can be rem oved at that tim e. As an p atients in the op en lobectom y grou p (p N S). The incid ence
alternative to d ischarging patients w ith chest tu bes, chem i- of p atients w ith atelectasis w as 2.1% after VATS lobectom y
cal p leu rod esis can be em ployed in the m anagem ent of and 3.3% after thoracotom y (p N S). The incid ence of post-
prolonged p ostoperative air leak. In a recent retrosp ective op erative intu bation w as significantly d ifferent, occu rring
analysis, 41 p atients w ith a p rolonged air leak u nd erw ent in 1.4% of p atients follow ing VATS lobectom y and 3.1% of
chem ical pleurod esis throu gh an ind w elling chest tube. p atients follow ing thoracotom y (p 0.0046). Although the
Sclerosis w as su ccessful in 40 of the 41 patients, w ith a need for intubation encomp asses post-operative com plica-
mean d u ration of air leak after sclerosis of 2.8 d ays. Five tions other than atelectasis and p neu m onia, these are m ajor
patients requ ired repeat sclerosis, and one patient d evel- reasons for reintu bation follow ing p u lm onary resection.
oped an em p yem a (40). In ad d ition to the su rgical ap p roach, there are other
m easu res to red u ce the incid ence of sp u tu m retention. The
m ost im p ortant tactic is sm oking cessation p rior to su rgery.
■ Sputum retention and pneumonia Vap orciyan et al. (45) fou nd in a retrosp ective analysis of
Poor airw ay hygiene is a significant life-threatening p rob- 237 p atients u nd ergoing p neu m onectom y that p atients
lem after chest su rgery. Acutely, it can cause hyp oxia, w ho continu ed to sm oke w ithin 1 month of the operation
tachycard ia, and hem od ynam ic em barrassm ent. Postop er- w ere at increased risk for d eveloping pneumonia and ad ult
ative p ain and com prom ised m ental statu s lead ing to an respiratory distress syndrome (ARDS). Chest physiotherapy,
inability to breathe d eep ly or cou gh are the m ain factors including coughing, early ambulation, incentive spirometry,
contribu ting to the retention of airw ay secretions. In m any and percussion with postural drainage, is the standard
cases, p ostop erative pain lead s to increased narcotic u se approach for postoperative prophylaxis and therapy for
w ith su bsequ ent com p rom ised m ental statu s and sp u tu m sputum retention. H ow ever, patients w ith recalcitrant spu-
retention. These airw ay secretions can go on to plu g the air- tum retention may require more invasive m easures such as
w ays, cau sing atelectasis, lobar collapse, p neum onia, and transcricoid saline injection to stim ulate coughing. As men-
resp iratory failu re. Patients at higher risk for p ostop erative tioned above, bronchoscopy may ultimately be required to
sp u tu m retention are cu rrent sm okers; p atients w ith a his- aspirate secretions and to stimulate a m ore vigorous cough.
tory of chronic obstructive pu lm onary d isease, cerebrovas- Many recom m end the liberal u se of minitracheostom ies in
cu lar accid ent, or ischem ic heart d isease; and those w ithou t high-risk patients as a form of p rophylaxis and treatm ent.
regional analgesia (41). In case-controlled stu d ies, the VATS The minitracheostomy tube allow s immed iate and repeated
app roach has been show n to be associated w ith less im m e- asp iration of the tracheobronchial tree. It is p laced percuta-
d iate p ostoperative pain com p ared to the thoracotom y neously through the cricothyroid m em brane either at the
app roach by an objective assessm ent of analgesic requ ire- tim e of su rgery or at the bed sid e p ostop eratively. In a
ments (42,43) and by su bjective scales (2). H ow ever, one p rosp ective rand omized trial of 102 high-risk patients,
prosp ective rand om ized trial com paring VATS lobectom y Bond e et al. (46) fou nd that p rop hylactic u se of m initra-
w ith thoracotom y show ed only a trend tow ard less nar- cheostom y significantly low ered the incid ence of sp u tu m
cotic u se that w as not statistically significant (44). The lack retention. Sim ilarly, Au et al. (47) rep orted a d ecreased
of statistical significance in this stu d y m ay have been need for su ction bronchoscop y in p atients w ho had u nd er-
related to sm all sam ple sizes and low statistical p ow er. In gone m initracheostom y placem ent.
general, how ever, it is believed that the VATS ap p roach
ind eed low ers postoperative pain and the need for analge-
sia. Dim inished p ain and a red u ced need for narcotic anal-
■ Atrial fibrillation
gesia shou ld low er the risk of spu tu m retention and poor The incid ence of atrial fibrillation (AF) follow ing noncar-
postop erative airw ay hygiene. d iac thoracic su rgery has been d ocu m ented to range from
As d ep icted in Table 29.3, the occu rrence of p neu m onia 10% to 40% (48,49). Althou gh the exact m echanism for the
after VATS resection in the Ced ars Sinai series w as 1.2%. In d evelop m ent of AF follow ing noncard iac thoracic su rgery
is not know n, a nu m ber of associated clinical features have less than that after thoracotom y. In the Ced ars Sinai series,
been d escribed . Major risk factors includ e ad vanced age, the incid ence of AF follow ing VATS resection w as 2.9%,
concom itant lu ng d isease, and extensive hilar d issection w hile it w as 14.4% in the Z0030 trial. In the Du ke VATS
(50–52). Althou gh generally transient and self lim iting, AF series, the incid ence of AF w as 10% (17). In the p ropensity-
can increase the length of stay and cost of hospitalization. m atched analysis of the STS d atabase d ep icted in Table
In ad d ition, it is associated w ith increased 30-d ay m ortality 29.4, AF occu rred in 7.3% of p atients after VATS lobectom y
and can lead to em bolic events (53). versu s 11.5% of p atients in the op en lobectom y grou p (p
Follow ing p u lm onary resection, m eticu lou s m anage- 0.0004). An im p ortant caveat in interp reting these results is
ment of flu id balance and electrolyte levels, particu larly that there m ay be a higher p ercentage of p erip heral tu m ors
potassiu m and m agnesiu m , are im perative to d ecrease the in the VATS grou p than in the thoracotom y grou p . As m en-
incid ence of AF. In ad d ition to su ch m easu res, the ability of tioned above, extensive d issection involving the hilum, as is
nu m erou s agents includ ing -blockers, calciu m channel required for central tu m ors, is associated w ith an increased
blockers, d igoxin, and am iod arone to provid e effective p ro- incid ence of AF.
phylaxis against the d evelop m ent of postoperative AF has
been investigated (54). Patients alread y taking -blockers
or calciu m channel blockers p re-op eratively shou ld con- ■ SUMMARY
tinu e on those m ed ications p ost-operatively. For p atients The revival of thoracoscopy for the m anagem ent of d is-
not taking a rate control agent p re-operatively, several eases of the chest is one of the m ost im p ortant recent
prospective rand om ized trials have d em onstrated a statis- ad vancem ents in thoracic su rgery. With p rop er ju d gm ent
tically significant red u ction in the incid ence of AF in and skill, the su rgeon can safely ap p ly this ap p roach to a
patients receiving p rophylactic calciu m channel blockers. w id e variety of card iothoracic p roced u res. Although the
In the most recent stu d y, pu blished by Am ar and col- ap p roach is m inim ally invasive, the risks for com plications
leagu es, the incid ence of AF w as red uced from 25% to 15% m u st not be overlooked . Anticip ation and attention to the
in patients receiving d iltiazem prop hylaxis (55). d etails of p atient selection, intraop erative techniqu e, and
When AF does occur, management decisions must be p ostoperative patient m anagem ent w ill help w ith p reven-
mad e quickly. H emod ynamically unstable patients require tion, early id entification, and su ccessfu l m anagem ent of
immediate electrical cardioversion. For stable patients, com p lications after thoracoscop y. Recent d ata from several
providers must choose between controlling the rate—gener- large series su ggest a d ecrease in the incid ence of atrial fib-
ally w ith beta or calcium channel blockers—and attempting rillation follow ing VATS lu ng resection com p ared w ith tho-
to chemically card iovert w ith amiod arone. Approximately racotom y. Im p rovem ents in the rates of p ostop erative air
50% of AF ep isod es w ill convert to norm al sinus rhythm leak and p neu m onia have been m ore m od est.
w ith rate controlling agents alone w ithin 12 hours, so this is
generally an ap p rop riate initial strategy (56). -blockers
need to be u sed w ith caution in patients w ith COPD, w ho ■ REFERENCES
rep resent a large p rop ortion of p atients u nd ergoing p u l- 1. Jacobeu s H C. Ueber d ie m öglichkeit d ie zytoskop ie bei u ntersu chu ng
monary su rgery. The u se of nonselective -blockers su ch as seroser hohlungen anzu w end en. Munch Med Wochenschr 1910;57:
propranolol m ay ind u ce or w orsen bronchospasm . 1- 2090–2092.
2. Dem m y TL, Cu rtis JJ. Minim ally invasive lobectom y d irected tow ard
selective blockers su ch as m etop rolol are generally w ell- frail and high-risk p atients: a case-control stu d y. Ann Thorac Surg 1999;
tolerated excep t in patients w ith severe COPD. Many 68:194–200.
patients, p articu larly those w ith other risk factors for 3. Lew is RJ, Caccavale RJ, Sisler GE, et al. One hu nd red consecu tive
patients u nd ergoing vid eo-assisted thoracic op erations. Ann Thorac
stroke, w hose AF p ersists beyond 48 hou rs, are started on Surg 1992;54:421–426.
anticoagu lation therapy for 4 to 6 w eeks. In ord er to 4. Boffa DJ, Allen MS, Grab JD, et al. Data from the Society of Thoracic
attem p t to avoid this and the attend ant bleed ing risk, m ost Surgeons General Thoracic Su rgery d atabase: the su rgical m anagem ent
of prim ary lu ng tu m ors. J Thorac and Cardiovasc Surg 2008;135:247–254.
patients w hose AF p ersists for m ore than 24 hours shou ld 5. Epstein SK, Faling LJ, Daly BD, et al. Pred icting com p lications after
und ergo an attem p t at chem ical card ioversion w ith am io- p u lm onary resection. Preoperative exercise testing vs a m u ltifactorial
d arone. This d ru g is successfu l in restoring sinus rhythm in card iopu lm onary risk ind ex. Chest 1993;104:694–700.
6. Melend ez JA, Carlon VA. Card iop u lm onary risk ind ex d oes not p red ict
up to 86% of postoperative patients (57). As w ith -blockers, com plications after thoracic su rgery. Chest 1998;114:69–75.
amiod arone need s to be used w ith caution in patients w ho 7. Brunelli A, Fianchini A, Gesu ita R, et al. POSSUM scoring system as an
have u nd ergone lung resection because of the risk of pu l- instru m ent of au d it in lu ng resection su rgery. Physiological and op era-
tive severity score for the enum eration of m ortality and m orbid ity. Ann
monary toxicity. It is generally not recom m end ed for u se in Thorac Surg 1999;67:329–331.
patients w ho have u nd ergone pneu m onectom y or w ho are 8. Melend ez JA, Barrera R. Pred ictive resp iratory com p lication qu otient
mechanically ventilated d u e to an unacceptably high rate p red icts p ulm onary com p lications in thoracic su rgical p atients. Ann
Thorac Surg 1998;66:220–224.
of ARDS d evelop ing w hen am iod arone w as u sed as a p ro- 9. Pierce RJ, Cop land JM, Sharp e K, et al. Preop erative risk evalu ation for
phylaxis in p neu m onectom y p atients (58). lung cancer resection: pred icted postoperative p rod u ct as a pred ictor of
With the d ecrease in p ostop erative p ain and the p resu rgical m ortality. Am J Respir Crit Care Med 1994;150:947–955.
10. DeCam p MM Jr, Jaklitsch MT, Mentzer SJ, et al. The safety and versatil-
su m ably low ered ad renergic state follow ing VATS resec- ity of vid eo-thoracoscopy: a p rosp ective analysis of 895 consecu tive
tions, it has been hoped that the incid ence of AF w ou ld be cases. J Am Coll Surg 1995;181:113–120.
11. Jaklitsch MT, DeCam p MM Jr, Lip tay MJ, et al. Vid eo-assisted thoracic 35. Fleisher AG, Evans KG, N elem s B, et al. Effect of rou tine fibrin glu e u se
su rgery in the eld erly. A review of 307 cases. Chest 1996;110:751–758. on the d u ration of air leaks after lobectom y. Ann Thorac Surg 1990;49:
12. Dem m y TL, Wagner-Mann CC, Jam es MA, et al. Feasibility of m athe- 133–134.
m atical m od els to pred ict success in vid eo-assisted thoracic surgery 36. Wong K, Gold straw P. Effect of fibrin glu e in the red u ction of p ost-
lu ng nod u le excision. Am J Surg 1997;174:20–23. thoracotom y alveolar air leak. Ann Thorac Surg 1997;64:979–981.
13. Jancovici R, Lang-Lazd u nski L, Pons F, et al. Com p lications of vid eo- 37. Fabian T, Fed erico JA, Ponn RB. Fibrin glu e in p u lm onary resection: a
assisted thoracic su rgery: a five-year exp erience. Ann Thorac Surg 1996; p rosp ective, rand om ized , blind ed stu d y. Ann Thorac Surg 2003;75:
61:533–537. 1587–1592.
14. Yim AP, Liu H P. Com p lications and failu res of vid eo-assisted thoracic 38. Wain JC, Kaiser LR, Johnstone DW, et al. Trial of a novel synthetic
su rgery: exp erience from tw o centers in Asia. Ann Thorac Surg 1996; sealant in preventing air leaks after lu ng resection. Ann Thorac Surg
61:538–541. 2001;71:1623–1628; d iscu ssion 1628–1629.
15. Krasna MJ, Deshm u kh S, McLau ghlin JS. Com p lications of thora- 39. Cerfolio RJ, Bass C, Katholi CR. Prosp ective rand om ized trial com p ares
coscopy. Ann Thorac Surg 1996;61(4):1066–1069. su ction versu s w ater seal for air leaks. Ann Thorac Surg 2001;71:
16. McKenna RJ, H ou ck W, and Fu ller CB. Vid eo-assisted thoracic surgery 1613–1617.
lobectom y: exp erience w ith 1100 cases. Ann Thorac Surg 2006;81: 40. Liberm an M, Mu zikansky A, Wright CD, et al. Incid ence and risk fac-
421–426. tors of p ersistent air leak after m ajor p u lm onary resection and u se of
17. Onaitis MW, Petersen RP, Bald erson SS, et al. Thoracoscop ic lobectom y chem ical p leu rod esis. Ann Thorac Surg 2010;89:891–897.
is a safe and versatile p roced u re: exp erience w ith 500 consecutive 41. Bond e P, McManu s K, McAnesp ie M, et al. Lu ng su rgery: id entifying
patients. Ann Surg 2006;244:420–425. the su bgrou p at risk for sp u tu m retention. Eur J Cardiothorac Surg
18. Roviaro G, Varoli F, Vergan i C, et al. Vid eo-assisted th oracoscop ic 2002;22:18–22.
m ajor p u lm on ary resection s: tech n ical asp ects, p ersonal series of 42. Yim AP, Ko KM, Chau WS, et al. Video-assisted thoracoscopic anatomic
259 p atien ts, an d review of th e literatu re. Surg Endosc 2004;18: lung resections. The initial Hong Kong experience. Chest 1996;109:13–17.
1551–1558. 43. Walker WS, Pu gh GC, Craig SR, et al. Continu ed exp erience w ith tho-
19. Allen MS, Darling GE, Pechet TV, et al. Morbid ity and m ortality of racoscop ic m ajor p u lm onary resection. Int Surg 1996;81:255–258.
m ajor pulm onary resections in patients w ith early-stage lung cancer: 44. Kirby TJ, Mack MJ, Land reneau RJ, et al. Lobectom y⎯vid eo-assisted
initial resu lts of the rand om ized , p rosp ective ACOSOG Z0030 trial. thoracic surgery versu s m u scle-sp aring thoracotom y. A rand om ized
Ann Thorac Surg 2006;81:1013–1020. trial. J Thorac Cardiovasc Surg 1995;109(5):997–1001.
20. Paul S, Altorki NK, Sheng S, et al. Thoracoscopic lobectomy is associated 45. Vaporciyan AA, Merriman KW, Ece F, et al. Incidence of major pul-
with lower morbid ity than open lobectomy: a propensity-matched analy- m onary morbidity after pneum onectom y: association with timing of
sis from the STS database. J Thorac Cardiovasc Surg 2010;139:366–378. sm oking cessation. Ann Thorac Surg 2002;73:420–425; discussion 425–426.
21. Yim AP, H o JK. Malfu nctioning of vascu lar stap le cu tter d u ring thora- 46. Bond e P, Papachristos I, McCraith A, et al. Sp u tu m retention after lu ng
coscopic lobectom y. J Thorac Cardiovasc Surg 1995;109:1252. op eration: p rosp ective, rand om ized trial show s su p eriority of p rop hy-
22. Watanabe A, Abe T, Yam au chi A, et al. Reinforcem ent of a bronchial lactic m initracheostom y in high-risk p atients. Ann Thorac Surg 2002;
stu m p in VATS lobectom y. Thorac Cardiovasc Surg 2000;48:242–243. 74:196–202; d iscu ssion 202–203.
23. Jones DR, Graeber GM, Tangu ilig GG, et al. Effects of insu fflation 47. Au J, Walker WS, Inglis D, et al. Percu taneou s cricothyroid otom y
on hem od ynam ics d u ring thoracoscop y. Ann Thorac Surg 1993;55: (m initracheostom y) for bronchial toilet: resu lts of therap eu tic and p ro-
1379–1382. p hylactic use. Ann Thorac Surg 1989;48:850–852.
24. Cooper JD. Techniqu e to red u ce air leaks after resection of em physe- 48. Roselli EE, Mu rthy SC, Rice TW, et al. Atrial fibrillation com p licating
m atou s lu ng. Ann Thorac Surg 1994;57:1038–1039. lu ng cancer resection. J Thorac Cardiovasc Surg 2005;130:438–444.
25. Venuta F, Rendina EA, De Giacom o T, et al. Technique to reduce air leaks 49. Vap orciyan AA, Correa AM, Rice DC, et al. Risk factors associated w ith
after pulmonary lobectomy. Eur J Cardiothorac Surg 1998;13:361–364. atrial fibrillation after noncard iac thoracic su rgery: Analysis of 2588
26. Eu gene J, Dajee A, Kayaleh R, et al. Red u ction p neu m onop lasty for patients. J Thorac Cardiovasc Surg 2004;127:779–786.
p atients w ith a forced exp iratory volu m e in 1 second of 500 m illiliters 50. Asam u ra H , N aru ke T, Tsu chiya R, et al. What are the risk factors for
or less. Ann Thorac Surg 1997;63:186–190; d iscu ssion 190–192. arrhythm ias after thoracic op erations? A retrospective m u ltivariate
27. H azelrigg SR, Boley TM, N au nheim KS, et al. Effect of bovine p ericar- analysis of 267 consecutive thoracic op erations. J Thorac Cardiovasc Surg
d ial strip s on air leak after stap led p u lm onary resection. Ann Thorac 1993;106:1104–1110.
Surg 1997;63:1573–1575. 51. Krow ka MJ, Pairolero PC, Trastek VF, et al. Card iac d ysrhythm ia fol-
28. Stam m berger U, Klep etko W, Stam atis G, et al. Bu ttressing the staple low ing p neu m onectom y. Clinical correlates and p rognostic signifi-
line in lung volu m e red u ction surgery: a rand om ized three-center cance. Chest 1987;91:490–495.
stu d y. Ann Thorac Surg 2000;70:1820–1825. 52. Ciriaco P, Mazzone P, Canneto B, et al. Su p raventricu lar arrhythm ia
29. Bru nelli A, Al Refai M, Monteverd e M, et al. Pleu ral tent after u p p er follow ing lung resection for non-sm all cell lung cancer and its treat-
lobectom y: a rand om ized stu d y of efficacy and d u ration of effect. Ann m ent w ith am iod arone. Eur J Cardiothorac Surg 2000;18:12–16.
Thorac Surg 2002;74:1958–1962. 53. Irshad K, Feld m an LS, Chu VF, et al. Cau ses of increased length of hos-
30. Oku r E, Kir A, H alezeroglu S, et al. Pleu ral tenting follow ing up p er pitalization on a general thoracic su rgery service: a prosp ective obser-
lobectom ies or bilobectom ies of the lung to prevent resid ual air space vational stu d y. Can J Surg 2002;45:264–268.
and prolonged air leak. Eur J Cardiothorac Surg 2001;20:1012–1015. 54. Sed rakyan A, Treasu re T, Brow ne J, et al. Pharm acologic p rop hylaxis
31. Robinson LA, Preksto D. Pleu ral tenting d u ring u p p er lobectom y for postoperative atrial tachyarrhythm ia in general thoracic su rgery:
d ecreases chest tu be tim e and total hosp italization d ays. J Thorac Car- evid ence from rand om ized clinical trials. J Thorac Cardiovasc Surg
diovasc Surg 1998;115:319–326; d iscu ssion 326–327. 2005;129:997–1005.
32. H and y JR Jr, Ju d son MA, Zellner JL. Pneu m op eritoneu m to treat air 55. Am ar D, Roistacher N , Ru sch VW, et al. Effects of d iltiazem p rop hy-
leaks and sp aces after a lu ng volu m e red u ction op eration. Ann Thorac laxis on the incid ence and clinical outcom e of atrial arrhythm ias after
Surg 1997;64:1803–1805. thoracic su rgery. J Thorac Cardiovasc Surg 2000;120:790–798.
33. De Giacom o T, Rend ina EA, Venu ta F, et al. Pneu m op eritoneu m for the 56. Am ar D. Postoperative atrial fibrillation. Heart Dis 2002;4:117–123.
m anagem ent of pleural air space problem s associated w ith m ajor pul- 57. Barbetakis N , Vassiliad is M. Is am iod arone a safe antiarrhythm ic to u se
m onary resections. Ann Thorac Surg 2001;72:1716–1719. in supraventricu lar tachyarrhythm ias after lu ng cancer su rgery? BMC
34. Cerfolio RJ, H olm an WL, Katholi CR. Pneu m op eritoneu m after con- Surg 2004;4:7.
com itant resection of the right m id d le and low er lobes (bilobectom y). 58. Van Mieghem W, Coolen L, Malysse I, et al. Am iod arone and the d evel-
Ann Thorac Surg 2000;70:942–946; d iscu ssion 946–947. opm ent of ARDS after lung su rgery. Chest 1994;105:164.
PART
IV
Complications of
Vascular Surgery
CHAPTER
30
Complications of Arterial Surgery

Gilbert R. Upchurch J r., J onathan L. Eliason, J ohn E. Rectenwald, and J ames C. Stanley
■ INTRODUCTION CEA varies w id ely, w ith established morbid ity and mortal-
ity stand ard s reported by experienced surgeons as being
The practice of surgery has evolved significantly over the last betw een 3% and 7% (16,17). This variation in postoperative
5 to 10 years with all specialties migrating toward minimally morbid ity and mortality may be second ary to the patients’
invasive approaches. Vascular surgery, in particular, has been p resenting symptoms, ranging from asymp tomatic carotid
affected by this trend with the majority of all arterial lesions d isease to frank stroke. It may also be influenced by the sur-
now being first treated u sing end ovascular techniqu es. For geon’s volume of carotid proced ures (18). Specific complica-
exam p le, in the past, aortoiliac occlu sive d isease (AIOD) tions (Table 30.1) and com plication rates (Table 30.2) from
w as managed primarily by aortobifemoral bypass, whereas centers of excellence d eserve ind ivid ual comment (19–23).
presently, this disease process is managed percutaneously
with angioplasty and stenting (1). It is predictable that, over ■ Early complications
time, with endovascular first approaches, the number of open
arterial operations performed w ill decline, thus impacting Myocardial Infarction
outcomes and complications as well as the training of future With the exception of stroke, card iac complications remain
surgeons. In addition to changes in practice patterns, the liter- the m ost com m on sou rce of m ortality after CEA. In an
ature reporting complications has shifted from primarily sin- important early stu d y, DeBakey and associates (24) noted
gle institution reports from centers of excellence to large the risk of periop erative m yocard ial infarction to be three
databases or registries w ith statewide or national samples tim es higher in patients w ho had hyp ertension or sym pto-
(2–11). While this shift in reporting allows increased power in matic carotid artery d isease than in those w ho d id not.
analyzing morbidity and mortality through coding across Myocard ial infarction is also the most common cause of late
large populations, the details or granularity of specific com- d eath in patients w ho have u nd ergone p rior CEA. The 10-
plications have become less visible in the resulting reports. year survival after CEA w hen p atients w ith coronary artery
Desp ite these shifts in vascu lar p ractice and rep orting, d isease und erw ent coronary artery bypass grafting (CABG)
m any of the life- and organ-threatening com p lications that p rior to CEA w as 55%, comp ared to 32% among those
occu r d u ring op en arterial su rgery rem ain the sam e (12). In w hose coronary artery d isease remained uncorrected (25).
the p resent chap ter, sp ecific com plications accom p anying Given this increased risk of myocardial infarction follow-
op erations on the extracranial carotid arteries, the aorta, ing CEA, many have advocated combined CEA and CABG
and the low er extremity arteries are highlighted , as these (26,27). While single institutional experiences have reported
three regions of the vasculatu re com prise the m ajority of acceptable results, current recommendations are that com-
arterial reconstru ctions. In ad d ition, stu d ies from large bined CEA–CABG be performed only in the setting of symp-
d atabases w ill d ocu m ent significant variability in p ractice tomatic internal carotid artery (ICA) disease. This subject
across a w id e range of com p lications. remains controversial. In contemporary series, w ith the more
frequent use of statins and antiplatelet agents, no evidence-
■ EXTRACRANIAL CAROTID ARTERY based data exist to establish guidelines (28). A recent study by
Brow n et al. suggested that stroke and death rates nationally
Althou gh carotid artery stenting is being u nd ertaken w ith
following CEA–CABG were higher than those reported from
increasing frequency (13,14), carotid end arterectomy (CEA)
isolated centers of excellence (29). In that study, the combined
rem ains one of the m ost com m only perform ed perip heral
CEA–CABG stroke and death rate w as 17.7%. Importantly,
vascular operations in the United States (15). To achieve its
the diagnosis of stroke in this series w as often delayed with
prim ary goal of stroke prevention, CEA must be performed
most strokes not involving the same hemisphere as the CEA.
w ith a low complication rate. The incid ence of stroke after
Cerebral Ischemia or Infarction
Gilbert R. Upchurch Jr.: University of Veginia, Char- This com plication m ay occur d uring end arterectom y as a
lottesville, VA Jonathan L. Eliason, John E. Rectenw ald , and result of internal carotid occlu sion and inad equate collat-
James C. Stanley: University of Michigan, Ann Arbor, MI eral flow to the brain. The risk of cerebral ischem ia is
331
332 Part IV• Complications of Vascular Surgery
Table 3 0 . 1 Com m on ea r ly a n d la t e com plica t ion s

follow in g ca rotid en da r t er ectom y
Early
Stroke
Myocardial infarction
Cranial nerve injury
Vagus nerve (recurrent laryngeal, superior laryngeal)
Hypoglossal nerve
Facial nerve (marginal mandibular)
Hemodynamic instability
Hypotension and bradycardia
Hypertension
Neck hematoma
Acute internal carotid artery thrombosis
Carotid dissection
Late FIGURE 30.1. Intraoperative duplex documenting common carotid artery
Recurrent Carotid Artery Stenosis (neointimal hyperplasia 0–24 months, dissection (single arrow ) and patent common carotid artery (double arrow)
recurrent atherosclerosis ( 24 months) that occurred secondary to the insertion of a shunt during carotid endarterec-
tomy (CEA).
Pseudoaneurysm (patch infection, suture line failure, arterial wall disruption)
greater am ong patients w ith contralateral carotid occlusion w as the m easu rem ent of carotid artery “stu m p p ressu re”
or prior stroke affecting the ip silateral hem isp here (30). or “back p ressu re” after the com m on and external carotid
A variety of techniqu es have been used to lessen cere- arteries are clam p ed . A 20-gau ge need le, connected to a
bral ischem ia d u ring CEA. One approach is to place an p ressu re transd u cer, is inserted into the carotid artery d is-
ind welling carotid shunt in all patients. However, many sur- tal to the com m on carotid artery clam p . A m ean stu m p
geons find the technical performance of this to be more diffi- p ressu re below 25 m m H g (33) or 50 mm H g (34) becom es
cult when a shunt is in place and believe that the process of an ind ication for the p lacem ent of a shu nt. H ow ever, neu -
shunt insertion may cause complications, including intimal rologic d eficits are know n to occu r in p atients w ho are
tears and dissections (Fig. 30.1), embolization of proximal op erated on u nd er regional anesthesia w ith stu m p p res-
atherosclerotic debris, and air emboli. Use of a shunt is su res above these levels (35).
appropriate in those patients who have inad equate cerebral Continu ou s electroencep halograp hic (EEG) monitoring
blood flow during carotid artery occlusion. Some surgeons d u ring carotid artery occlu sion has been p rop osed to p ro-
prefer to perform CEA und er local or regional anesthesia, vid e a sensitive techniqu e for m onitoring the ad equ acy of
and if carotid cross-clamping initiates neurologic dysfunc- cerebral blood flow. Ap p roxim ately 15% of p atients evalu-
tion, then a shunt is inserted (31,32). The use of selective ated in this fashion w ill requ ire shu nting d u ring CEA (36).
shunting under regional anesthesia appears to offer a reason- Som e p atients w ith stu m p p ressu res above 75 m m H g w ill
able means of recognizing intraoperative cerebral ischemia d evelop EEG evid ence of cerebral ischem ia. In one stu d y,
during carotid clamping. In addition, this approach may the EEG rem ained norm al in 39 ou t of 1,009 p atients sub-
reduce cardiovascular complications, such as perioperative jected to end arterectom y u nd er local anesthesia w ho
blood pressure instability accompanying general anesthesia. show ed obviou s cerebral ischem ia (37). In 52 other p atients
One of the original techniqu es u sed for assessing the in this series, the EEG becam e abnorm al, bu t the clinical
ad equ acy of cerebral blood flow in anesthetized p atients statu s d id not su ggest cerebral ischem ia. Thu s, w hile EEG
Table 3 0 .2 Ea r ly com p lica t ion s follow in g ca r ot id en d a r t er ect om y from con t em p ora r y, la r ge,
sin gle in st it u t ion a l ser ies
Carotid
Primary Year of Endarterectomies Mortality Cranial Nerve Postoperative
Author Report Study Period Performed (N) (%) Stroke (%) Injury (%) Bleeding (%)
Ballotta 2004 1990–2002 1,150 0.3 0.9 4.5 Not stated
Conrad 2003 1990–1999 1,045 0.9 3.0 2.5 1.7
Darling 2003 1994–1999 3,429 1.1 1.7 0.6 2.3
Ecker 2003 1988–2000 1,000 0.9 1.0 0.7 Not stated
Illig 2003 1993–2000 1,168 0.6 2.7 0.8 2.7
Chapter 30 • Complications of Arterial Surgery 333
may provid e a m eans of m onitoring cerebral p erfusion perioperative risk factors for the development of cerebral
d u ring CEA, it is not consistently reliable. hyperperfusion syndrome includes long-standing hyperten-
A second cause of perioperative stroke is the embolization sion, diabetes mellitus, increased age, recent contralateral
of the throm bu s or atherom atou s d ebris from w ithin the CEA ( 3 months), high-grade ipsilateral carotid stenosis
d iseased carotid artery. This com plication m ay occu r d u r- with poor collateral flow, contralateral carotid occlusion, and
ing the d issection of the carotid artery, placem ent or release refractory postoperative cerebral hyperperfusion. No specific
of a clamp , or from platelet aggregates accum u lating at the therapies have been documented to adequately treat patients
end arterectom y site d u ring the operation or in the imm ed i- with cerebral hyperperfusion (41). However, strategies
ate p ostop erative period . Carotid artery d issection shou ld involving the prevention of cerebral edema w ith head eleva-
always be performed with minimal manipulation of the inter- tion, limiting fluid resuscitation, and aggressively treating
nal carotid artery, using the so-called “no touch technique.” hypertension seem justified. As cerebral hyperperfusion syn-
Similarly, at the completion of the endarterectomy, the vessel drome can result in severe brain edema, intracerebral hemor-
lumen should be carefully irrigated with heparinized saline rhage, and d eath, treatment should be directed toward
and all pieces of loose intima or media removed. Periopera- red ucing blood pressure and limiting excessive increases in
tive use of aspirin or other antiplatelet agents reduces the cerebral perfusion.
deposition of platelets on the surface of the endarterec-
tomized vessel. The use of statins has also been associated Cranial Nerve Injury
with a reduced incidence of stroke following CEA (38). Cranial nerve inju ry is not an u ncom m on com p lication fol-
A third cause of stroke follow ing CEA is acute throm bo- low ing CEA, accom p anying as m any as 39% of these proce-
sis of the internal carotid artery. This com plication resu lts d u res (42). Certain cranial nerve inju ries are not d etectable
most often from su bintim al hem orrhage u nd er a loose flap u p on casu al exam ination, in that one-third of these injuries
or inad equ ate control of p roxim al or d istal end arterectom y p rod u ce no clinical sym p tom s su ch as hoarseness, d iffi-
end p oints. The com pletion d u plex of the carotid artery has cu lty in sw allow ing, or changes in sp eech (42,43). The m ost
altered the trad itional algorithm for the treatm ent of acu te com m on inju ries involve the recu rrent laryngeal nerve
ICA throm bosis since it has been su ggested that a norm al w ith su bsequ ent hoarseness, and the hyp oglossal nerve
com pletion d u plex eliminates the need to im m ed iately w ith the resultant tongue d eviation tow ard the sid e of the
retu rn the p atient to the operating room (39). Intraop era- inju ry and d ifficu lty in m astication. Recu rrent laryngeal
tive u se of a carotid d u p lex has recently gained favor over nerve inju ry is u su ally a m anifestation of inju ry to the ipsi-
“on-table” cerebral angiography. H ow ever, one cou ld not lateral vagu s nerve, m ost often by a retractor or clam p s.
be fau lted for an aggressive ap proach and for retu rning all Other inju ries involve the superior laryngeal nerve w ith a
patients su sp ected of carotid throm bosis to the op erating resultant voice fatigue and the m arginal m and ibu lar nerve
room in the setting of acu te stroke after CEA. w ith a d roop ing of the low er lip . Less com m only inju red
A final cau se of p ostend arterectom y stroke is intracere- nerves are the greater au ricu lar nerve, w hich resu lts in
bral hem orrhage. This p roblem typically occu rs on the sec- nu m bness over the low er earlobe, the sp inal accessory
ond or third d ay after carotid end arterectom y, often d u ring nerve and the glossop haryngeal nerve w ith shou ld er
a p eriod of severe hyp ertension (40). N eurologic d eficits shru gging and d ifficu lty sw ollow ing respectively.
occu rring on the second or third p ostop erative d ay shou ld Many cranial nerve inju ries are second ary to traction
lead to d u plex scanning or angiography to ensu re the and u su ally resolve w ithin 6 m onths. H ow ever, bilateral
patency of the carotid artery. If a significant carotid artery inju ries m ay be severely d isabling or even life-threatening.
d efect is id entified , the patient shou ld be retu rned to the This is particularly tru e in the case of bilateral recu rrent
operating room and the vessel repaired . Com pu ted tom og- laryngeal nerve inju ry. All p atients w ho u nd ergo CEA
rap hy (CT) or m agnetic resonance im aging (MRI) of the should be subjected to careful cranial nerve exam ination
brain shou ld be obtained if the carotid artery is norm al. The before and after op eration. In ad d ition, bilateral CEAs
presence of intracerebral hem orrhage carries a p oor p rog- should not be p erform ed sim u ltaneously but shou ld be
nosis, and som e have recom m end ed neu rosu rgical evacu a- staged follow ing ap propriate neurologic exam ination,
tion of the hem atom a in selected p atients (32). inclu d ing ind irect laryngoscop y betw een op erations.
Cerebral hyperperfusion synd rome is a rare but poten-
tially lethal complication follow ing either CEA or carotid Hematoma
stenting (41). Follow ing the carotid intervention w ith Hematoma after CEA, although rare, may, in part, reflect the
improved blood flow and pressure, patients w ith this compli- fact that many patients receive preoperative antiplatelet
cation develop a constellation of symptoms, including ipsi- agents and heparin anticoagulation intraoperatively. Reoper-
lateral migraine-like headache, seizure, and transient focal ation for the evacuation of a hematoma or control of bleeding
neurologic deficits in the absence of frank cerebral ischemia. follow ing CEA occurs in only 1% of experienced practices
While this synd rome is defined by the clinical picture, the (44). Nevertheless, acute airway compromise may occur and
diagnosis is confirmed with imaging techniques. The inci- opening of the neck at the bed side on rare occasions may
dence of cerebral hyperperfusion synd rome is reported to be obviate the need for the creation of an emergent surgical air-
between 0.4% and 14%. A partial list of preoperative and w ay, allowing for an orderly return to the operating room.
Hypertension and Hypotension

H yp ertension and hypotension associated w ith CEA have
been attribu ted to a num ber of factors. H ypotension and
brad ycard ia are thou ght to be second ary to increased
barorecep tor activity d u ring the d issection of the carotid
artery or stim u lation of the sinus nerve follow ing the
rem oval of a rigid atherosclerotic plaqu e. H ypertension
may be cau sed by the interrup tion of the carotid sinu s
nerve activity d u e to its transection or changes in the arte-
rial w all com p liance. In an early stu d y (45), severe hyp er-
tension com p licated 19% of carotid end arterectom ies and
hyp otension affected an ad d itional 28% of cases. Su ch
alterations in blood pressu re w ere associated w ith a 9%
incid ence of p ostop erative neurologic d eficits, in contrast
to no neu rologic com p lications am ong norm otensive
patients. In ad d ition, the evolu tion of care of the p atient
w ho u nd ergoes CEA from an inp atient to an ou tp atient or
d u ring a 23-hou r stay visit is prim arily d epend ent on the
avoid ance of hyp o- or hypertension (46). Postop erative
hyp ertension is m uch m ore com m on in chronically hyper-
tensive p atients. Patients w ho have u nd ergone bilateral
CEA are p articu larly p rone to d evelop hyp ertension, and in
ad d ition, ap p ear to lose their norm al com pensatory resp i-
ratory and circu latory responses to hypoxia (47). Becau se
of the p otential severity of these com plications, hyp erten- FIGURE 30.2. Recurrent carotid stenosis secondary to intimal fibroplasia
following carotid endarterectomy.
sion shou ld be controlled and volu m e d eficits corrected in
all patients p rior to elective CEA (45).
Reports d ocu m enting the rates of early com plications enchymal cells, p erhaps of smooth-muscle origin (Fig. 30.2).
from large, national, or state d atabases have gained p op u - The second typ e u su ally d evelop s after 2 years and repre-
larity in recent years. Table 30.3 d ocu m ents the resu lts of sents recu rrent atherosclerosis. The mechanism s by w hich
four large stu d ies in w hich hard end points, such as m ortal- these tw o form s of recu rrent carotid stenosis evolve are
ity, stroke, and m yocard ial infarction rates, are rep orted u nknow n, bu t there is evid ence that they rep resent a con-
(2–5). H ow ever, these stud ies often lack granu larity, and d o tinu u m and are a consequ ence of vessel w all inju ry (50). In
not report on com plications such as cranial nerve inju ry or this regard , extensive p latelet aggregation w ithin the
hem atom a rates. end arterectomized vessel m ay be associated w ith the
release of variou s grow th factors that act as a stim u lu s to
■ Late complications cell p roliferation. Asp irin and other antip latelet agents m ay
p revent p latelet aggregation w ith ad herence to the vessel
Recurrent Carotid Stenosis w all, yet there is little clinical evid ence that these d ru gs
Sym p tom atic recu rrence of carotid stenosis occu rs in less p revent carotid stenosis (48). Other factors id entified w ith
than 3% of p atients, w hereas the asym ptom atic recu rrence hyp ercellular responses after CEA inclu d e hypercholes-
rate is betw een 9% and 12% (48). Tw o form s of recu rrent terolem ia and fem ale gend er (51). The incid ence of recur-
carotid d isease have been id entified (49). One type occu rs rent carotid stenosis is three tim es higher in w om en than it
w ithin the first 2 years second ary to neointim al fibrop lasia. is in m en. Recu rrent carotid stenosis also occu rs m ore often
This lesion is characterized by the p roliferation of m es- in patients w ith d iffu se vascu lar d isease and has been m ost
Table 3 0 .3 Com plica tion rates from state an d n ation al databases followin g ca rotid en darterectomy (CEA)
Primary Author Year of Report Study Year CEA (N) Mortality (%) Stroke (%) Myocardial Infarction (%)
McPhee 2008 2005 122,986 0.57 1.1 Not stated
Sidawy 2009 2005–2007 3,259 0.73 1.68 0.58
Halm 2009 1998–1999 8,662a 1.1 3.1 Not stated
Vogel 2009 2005 73,929 0.26 2.66 2.34
a
Only white patients are included in this table since cumulative numbers for all races were not included in this report.
FIGURE 30.3. Computed tomography angiography (CTA) documenting high

grade stenosis (arrow) distal to a previous carotid endarterectomy (CEA).
striking in those w ith a history of heavy cigarette sm oking FIGURE 30.4. False aneurysm of right carotid artery following carotid
(48). Carotid p atching has also been d ocu m ented to endarterectomy with patch graft closure.
d ecrease the incid ence of recurrent carotid stenosis, w ith
autogenou s sap henou s vein patches outperform ing syn- m anagem ent of carotid artery false aneu rysms u su ally
thetic p atches (52). entails arterial closure w ith a saphenou s vein patch or
H igh-grad e stenoses or sym p tom atic recu rrent carotid carotid artery rep lacem ent w ith an interp osition vein graft.
artery sten oses shou ld be assessed by CT an giograp hy
(Fig. 30.3) or conventional cerebral arteriograp hy and ■ AORTA
treated . Op erations for recu rrent carotid artery stenosis can
be d em and ing, p articu larly those that occur w ithin the first Mod ern op en aortic reconstru ction is one of the m ost com -
2 years. In these cases, there is u sually extensive scarring p lex vascu lar su rgery p roced u res, w ith significant varia-
arou nd the artery, m aking the d issection challenging. Sp e- tion in m ortality and m orbid ity based on both patient and
cial attention shou ld be paid to the id entification and p rovid er variables (56,57). The nu m ber of aortic proce-
avoid ance of cranial nerve inju ry. Patch-graft angiop lasty is d u res has been im p acted by both the aging of society, as
recom m end ed in closing the carotid arteriotom y in reop er- w ell as by the introd uction of end ovascu lar aortic repair.
ations. Rep lacem ent of the affected carotid artery w ith an The im portance of com orbid d iseases on m ortality associ-
ePTFE or sap henou s vein graft m ay be necessary (53). ated w ith elective and em ergent abd om inal aortic
Carotid stenting as a m eans to lessen the risks accom p any- aneu rysm (AAA) rep air are im p ortant and have been w ell
ing reoperation has gained favor in the treatm ent of recu r- d ocu m ented in tw o large p op u lation-based stu d ies (58,59).
rent carotid artery stenoses (54). Sp ecific com p lications (Table 30.4) and com p lication rates
(Table 30.5) are d iscu ssed ind ivid u ally (60–63).
False Aneurysm
False aneurysm form ation follow ing CEA is a particu larly ■ Early complications
rare com p lication, occurring in less than 0.05% of cases
(55). Cau ses of aneu rysm formation includ e sutu re line fail- Myocardial Ischemia and Infarction
ure, arterial w all d egeneration, and infection, particu larly Card iac com p lications are the m ost relevant cau ses of p eri-
of a p atch u sed in the arteriotom y closu re (Fig. 30.4). The op erative m ortality and late p ostop erative d eath follow ing
Table 3 0 . 4 Com m on ea r ly a n d la t e com plica t ion s patients w ith both symptomatic coronary and aneurysm
follow in g in fra r en a l a bd om in a l d isease. Mod ern intraoperative and postoperative care (60)
a or t ic a n eu r ysm r ep a ir includ es hemod ynam ic assessm ents w ith Sw an-Ganz pul-
monary artery catheters and transesophageal echocard iog-
Early raphy. Such monitoring has been reported to result in less
Myocardial infarction than a 2% perioperative mortality rate, and more impor-
Hemorrhage tantly, a 75% 5-year survival rate w ith only a 5% late cardiac
Respiratory failure mortality (70). These d ata contrast w ith a 25% to 35% card iac
Renal failure
mortality at 5 years follow ing m ajor aortic surgery noted in
Embolization
older series.
Mesenteric ischemia
Spinal cord ischemia
Ureteral injuries Hemorrhage
Chylous ascites H emorrhage may contribute to early morbid ity and mortal-
Late ity follow ing elective aortic surgery (71). Certain factors m ay
Graft infection (aortoduodenal fistula, anastomotic pseudoaneurysm) be associated w ith excessive operative blood loss d uring
Graft thrombosis aortic surgery. Venous anomalies, w hich occur in approxi-
Structural graft failure mately 5% of cases, such as the duplication of the inferior
Aneurysm proximal/distal to repair vena cava, circumferential renal vein, left-sided inferior vena
Abdominal wall hernia cava, and the retroaortic left renal vein may be easily injured
Impotence/retrograde ejaculation and lead to consid erable hemorrhage. The absence of an
anterior left renal vein is ind icative of a retroaortic left renal
vein, w hich may be torn during the posterior dissection of
aortic su rgery (64). Fatal myocard ial infarction accou nted the proximal infrarenal aorta. Particularly d isposed to injury
for 37% of early p ostoperative d eaths am ong 343 consecu - is the posteriorly located small lumbar vein originating from
tive p atients w ith abd om inal aortic aneu rysm s treated at a the mid portion of the left renal vein. Careful ligation of all
major referral center (65). In this regard , severe coronary vessels transected w hile exposing the aorta not only red uces
artery d isease w as p resent in 36% of 1,000 patients w ith operative blood loss but also lessens the incidence of trou-
AAAs w ho w ere subjected to m and atory coronary arteri- blesome postoperative hemorrhage. Similarly, careful tem-
ography before rou tine aortic surgery. Recent resu lts from perature control and blood component replacement w ill
the sam e institu tion su ggests that the rate of this d read ed lessen the incid ence of coagulopathies associated w ith exces-
com plication has m arked ly d ecreased w ith only 1% of sive blood loss and the administration of large quantities of
1,135 p atients su staining a periop erative m yocard ial infarc- banked blood . The benefits of using autotransfusion d evices
tion follow ing op en AAA repair (62). d uring aortic surgery repair has been supported by some
Aggressive preoperative cardiac management of patients (72), but contested by others (73).
w ho are to u nd ergo aortic op erations inclu d es selective Accurate blood and flu id replacement is im portant in
exercise or chem ical stress testing, as w ell as coronary arte- p reventing hypotension associated w ith aortic unclam ping
riography (66), and in select cases, it includes preoperative (64). Vasod ilators u sed to d ecrease p erip heral resistance
coronary artery angioplasty or bypass. The criteria for pur- and afterload d u ring aortic cross-clam p ing shou ld be d is-
suing extensive card iac stud ies have been w ell established continu ed p rior to d eclam p ing so that fu rther d ecreases in
(67,68). The combined performance of CABG and AAA p erip heral resistance upon d eclam ping w ill not resu lt in
repair has been reported (69) but can be ad vocated only in hyp otension. Rep erfu sion of ischem ic extrem ities releases
Table 3 0 .5 Ea r ly com p lica t ion s follow in g in t a ct a bd om in a l a or t ic a n eu r ysm r ep a ir from

con t em p ora r y ser ies
Patients
Undergoing Myocardial Acute
Primary Year of Study Elective Open Mortality Infarction Renal Respiratory Ischemic
Author Report Period AAA Repair (N) (%) (%) Failure (%) Failure (%) Colitis (%)
Bertges 2000 1994–1999 314 1.9 2.9 4.5 7.3 1.6
Elkouri 2004 1999–2001 261 1.2 5.4 4.2 7.7 Not stated
Hertzer 2002 1989–1998 1,135 1.2 1 1.7 4 1
Menard 2003 1990–2000 572 1.0 1.2 2.3 5.2a 0.2
a
Number reflects clinically significant pneumonia only, not additional sources of respiratory failure.
vasoactive su bstances that have an ad verse effect on blood

pressu re, such as lactic acid, potassium, and other vasoactive
products, into the systemic circulation (74). An expeditious
operation, slow pelvic and lower extremity reperfusion, and
good communication with the anesthesiologist should lessen
hazardous reperfusion events.
Renal Insufficiency
Renal insu fficiency accom p anying aortic surgery is m ore
likely to occur w ith hem orrhagic hypotension and inad e-
qu ate blood rep lacem ent (75). It is associated w ith m ore
than 30% m ortality in the setting of an elective aneu rys-
mectomy (58). Tem porary or perm anent renal failu re
affects m ore than 70% of patients w ith ruptured AAAs. In
this setting, it is associated w ith a 53% m ortality rate for
being d irectly related to total aortic clam p tim e—the tim e
d elay from actu al ru pture to aneurysm resection—as w ell
as blood loss (76). Renal failure is also a relatively com m on
com plication follow ing the resection of thoracoabd om inal
aneu rysms (77). Postoperative d ialysis is required in 5% of
these p atients w ho have norm al p reop erative renal fu nc-
tion and 17% of those w ith preop erative seru m creatinine
levels 2 m g/ d L (78). Intraoperative renal artery p erfu sion
w ith cold balanced salt solu tions m ay have a p rotective
effect in those w ith im paired preoperative renal function,
bu t it d oes not app ear to protect against d isturbances in
renal fu nction am ong p atients w ith norm al p reop erative
fu nction. FIGURE 30.5. CTA following aortobifemoral bypass documenting missing
popliteal artery, consistent with a decrease in ankle–brachial indices (ABIs),
secondary to embolism from debris in the femoral artery.
Embolization
Low er extrem ity em bolization is a seriou s com p lication of
aortic su rgery, often from the d islod gem ent of m u ral Colon Ischemia
d ebris d u ring op erative d issection or from accu m u lated Colon ischemia has been reported to accompany 0.2% to
throm bu s in the static colu m n of blood above the aortic 10% of AAA repairs (80,81). Intestinal ischemia is less com-
clam p (Fig. 30.5). Althou gh larger em boli can often be mon follow ing aortofemoral bypass or aortoiliac endarterec-
retrieved w ith a balloon catheter, sm aller atheroem bolic tomy for occlusive d isease. A prospective study (82) using a
p articles cannot be rem oved and w ill lead to m icrovascu - routine colonoscopy documented colon ischemia in 4.3% of
lar occlu sions, p rod u cing cu taneou s ischem ia inclu d ing elective aortic proced ures for occlusive d isease, 7.4% for
so-called “trash foot” if the d igital arteries are affected aneurysmal disease, and 60% when treating ruptured AAAs.
(79). The frequ ency of su ch com p lications has been gener- Overall mortality for colon ischemia in this setting is approx-
ally accep ted to range from 2% to 5%. imately 50% and approaches 90% w ith transmural infarc-
Technical m aneu vers to lessen the com p lication of tion. Colonic ischemia is more likely to accompany aortic
em bolization d uring aortic su rgery inclu d e carefu l d issec- resection w ith improper inferior mesenteric artery ligation,
tion of iliac vessels p rior to the clam p application, d istal ruptured aneurysms with arterial and venous compression
iliac clam p application prior to a proxim al aortic clam p by hematoma w ithin the mesocolon, operative trauma to
app lication, effective system ic heparin anticoagu lation, vessels w ithin the mesocolon, hypotension w ith diminished
thorou gh asp iration of the lu m en of the aortic p rosthesis perfusion of colon blood vessels, inad equate collaterals to
prior to im p lantation to rem ove any ad herent blood or the inferior mesenteric arterial circulation, and damage to
d ebris, p revention of stagnant blood accu m ulation in the collateral vessels when they do exist. The presence of a large
graft w hile the anastom oses are being perform ed , as w ell meandering mesenteric artery, carrying blood from the left
as vigorou s flu shing of the p roxim al and d istal vessels colic branch of the inferior mesenteric to the left branch of
prior to reestablishm ent of extrem ity arterial blood flow. the midd le colic artery just beyond its origin from the supe-
Patients w ith atheroem bolism experience extrem e p ain in rior mesenteric artery, is indicative of superior mesenteric
the feet and toes associated w ith an exaggerated inflam m a- artery occlusive d isease. In such cases, the reconstruction of
tory resp onse to cholesterol em boli. Ep id u ral anesthesia the superior mesenteric artery or inferior mesenteric artery
may help to blunt the sympathetic vasoconstrictive response reimplantation into the vascular graft may be necessary to
associated w ith this typ e of ischem ic pain. avoid colon ischemia. Although rarely measured , inferior
mesenteric artery back p ressu re of less than 40 m m H g in

p atients u nd ergoing AAA resection also su ggests a need
to restore antegrad e flow in this vessel (83). Rou tine reim -
p lantation of the inferior m esenteric artery into the aortic
graft has been ad vocated by som e, bu t su ch d oes not
ensu re the p revention of significant m esenteric ischem ia
(84). Intraop erative Dop p ler confirm ation of blood flow at
both the m esenteric and antim esenteric bord ers of the sig-
m oid colon is a u sefu l m eans of confirm ing the ad equ acy
of collateral blood flow to the colon follow ing aortic
reconstru ction.
Patients w ith severe colon ischem ia often p resent 1 to
2 d ays postoperatively w ith liquid brow n or blood y d iar-
rhea, left-sided abdominal pain, abdominal d istension, aci-
dosis, oliguria, and fever. Less severe ischemia may not
become apparent until 5 to 7 d ays after surgery. Any patient
w ho und ergoes aortic surgery and d evelops these signs and
symptoms requires urgent colonoscopy. If transm ural infarc-
tion is suspected , laparotomy and resection of the affected
colon should be und ertaken w ith the creation of a proximal
colostomy and a H artmann’s pouch or mucous fistula d is-
tally. Mucosal ischemia, if not severe, may be managed by
hydration, hemodynamic stabilization, and the intravenous
administration of antibiotics. Mucosal ischemia may resolve
w ithin 7 to 10 d ays, but close monitoring w ith repeated
colonoscopy is ind icated . If d eeper structures are affected
and perforation does not occur, stricture formation may
occur in 6 to 10 w eeks. In one stud y of 472 cases of AAA
repair, 33% of the elective mortality w as associated w ith
FIGURE 30.6. Ureteral injury (arrows) due to excessive dissection and
acute gastrointestinal complications, of w hich ischemic coli- devascularization during aortic reconstruction leading to an ischemic stenosis.
tis w as the m ost common (80).
Spinal Cord Ischemia arterial blood p ressu re below the aortic cross-clam p. In
Spinal cord ischem ia, accom panies 0.2% of elective AAA ord er to m aintain at least a 10 m m H g grad ient, the w ith-
repairs and 2% of em ergent repairs of rup tu red aneu rysm s. d raw al of sp inal flu id to d ecrease intrasp inal canal p res-
Sp inal cord ischem ia is not p red ictable from p reop erative su re has been ad vocated (88,89). Sp inal cord m onitoring,
arteriogram s (85). Am ong 51 reported cases of postop era- u sing som atosensory evoked p otentials, as w ell as variou s
tive sp inal cord ischem ia follow ing abd om inal aortic su r- d ru g interventions have also been p rop osed to lessen the
gery, 45% occu rred w ith ru p tu red aneu rysm s, 33% w ith risk of this com p lication (90,91).
elective aneu rysm ectom y, and 20% w ith treatm ent for
AIOD (86). Ureteral Injuries
Spinal cord ischemia is more common follow ing thora- Ureteral injuries m ay occur d uring d issection and rep air of
coabd ominal aneurysm repair, occurring in approximately large aortic or iliac aneu rysm s, p articu larly in the presence
10% of these p roced ures, and in more than 40% of p atients of inflam m atory aneu rysm s (92) (Fig. 30.6). Most u reteric
w ith aneurysms caused by d issections (78). The primary inju ries are associated w ith d evascu larization d u e to the
cause of spinal ischemia has been attributed to the interrup- excessive or inju d iciou s skeletonization of the u reter. The
tion of the cord ’s blood supply. The clamping of the inad vertent inclu sion of a p ortion of the u reteral w all in
supraceliac aorta and concomitant hypotension appear to the sutu re closu re of tissues over the im p lanted aortic graft
contribu te to this complication. The former relates to the is an infrequ ent cau se of u reteral inju ry. Aortofem oral graft
aortic origin of the sp inal artery of Ad am kiew icz, w hich has lim bs shou ld be tu nneled p osterior to the u reters so as to
been fou nd as high as T8 and as low as L4. Im paired p revent com pression of the u reters.
hypogastric artery perfu sion, em bolization, and postop era-
tive hypotension may also cause low er spinal cord ischemia Large Administrative Databases
d uring abd ominal aortic surgery (87). Early com p lication rates d erived from large ad m inistrative
N o universal intervention has been found to p rotect d atasets of p atients u nd ergoing op en AAA rep air m ay now
against sp inal cord ischem ia. Recent research has centered be com pared to com plication rates for patients und ergoing
on the grad ient betw een spinal cord pressure and system ic end ovascu lar AAA rep air (EVAR) (Table 30.6) (6–10). It is
Table 3 0 . 6 Com p lica t ion r a t es fr om st a t e a n d n a t ion a l d a t a ba ses follow in g op en AAA r ep a ir

Cardiac Renal Respiratory Mesenteric
Primary Year of Study Patients Mortality Complication Complication Complication Ischemia
Author Report Period (N) (%) (%) (%) (%) (%)
Dillavou 2006 1994–2003 Roughly Decreased Not stated Not stated Not stated Not stated
28,000/year from 5.57
to 3.20
Giles 2009 2001–2004 32,056 5.3 Not stated Not stated Not stated Not stated
Schermerhorn 2008 2001–2004 22,830 4.8 9.4 10.9 17.4 2.1
Schwarze 2009 2001–2006 Decreased 3.19–4.24 7.57–9.68 5.74–11.08 15.2–20.8 Not stated
from 17,784 to
8,451/year
clear from these reports that, over tim e, the resu lts of op en not only on p lates bu t also in broth follow ing sonication
AAA rep air have im proved w ith low er m ortality rates. The (97). A nu m ber of tests m ay be p erform ed if a d iagnosis of
im p act of EVAR on the results of open AAA rep air, over graft infection is su sp ected , inclu d ing ind iu m -labeled
tim e, w ill be im portant to continue to follow, as m any of w hite blood cell im aging, MRI, and CT (Fig. 30.7). Direct
the p atients w ho p resently u nd ergo op en rep air are not op erative insp ection of the graft su sp ected to be infected
anatom ically ap p ropriate cand id ates for EVAR. In ad d i- m ay be requ ired to establish the p resence or absence of
tion, the training of su rgeons to perform open rep air w ill be infection. Failu re of graft incorp oration, accum u lation of
challenged by the ever increasing use of end ovascular tech- p erigraft flu id or d ebris, and a Gram stain p rovid ing evi-
nology to m anage aortic p athology. d ence of bacteria or leu kocytes all su p p ort the existence of
a graft infection.
The trad itional m eans of treating an infected graft is
■ Late complications first its rem oval, follow ed by second ary revascu lariza-
Prosthetic Aortic Graft Infection tion. In m ost series, this m ethod has been su p p lanted by
revascu larization first, either d u ring the sam e op eration
This com p lication affects betw een 1% and 6% of as th e graft rem oval or staged 2 to 5 d ays p rior to graft
im p lanted aortic grafts, w ith an average incid ence of 0.7% rem oval (98). Significant d ifferences in m ortality or new
for aortoiliac grafts and 1.6% for aortofem oral grafts (93). graft in fection s d o not occu r u sing this latter techn iqu e;
Mortality from infected grafts in the aortoiliac or how ever, there is a significan tly low er rate of extrem ity
aortofem oral p ositions can be as high as 50%. H ow ever, am p u tation. The u se of the su p erficial fem oral vein to
in a series of 92 p atients w ith 84 infected aortoiliac or rep lace the infected aortic graft has been recently ad vo-
aortofem oral grafts, m ore than 70% w ere cu red of th eir cated (99). Others have su ggested the u se of antibiotic-
infection, with follow -up ranging from 10 months to 12 years soaked grafts or cryop reserved grafts or extra-anatom ic
(94). In this series, 25% of the p atients requ ired am p u ta- byp asses (100,101).
tion, m ost at a level above the knee. Thu s, am p u tation
m orbid ity rem ains high, even w ith su ccessfu l m anage-
m ent of the graft infection.
Factors contribu ting to graft infection inclu d e intraop-
erative contact of the graft w ith the skin, contam inated
lym p hatics, intraoperative breaks in sterile techniqu e,
extension from w ound sep sis, arterial w all infection, and
transient bacterem ias. Bacteria are fou nd 43% of the tim e in
aneu rysm throm bu s and aortic w all specim ens cu ltu red
d u ring rou tine AAA repair w ith the m ost comm on organ-
ism being Staphylococcus epidermidis (95).
A significant increase in graft infection occurs in
patients w ith p ositive arterial w all cultu res u nd ergoing
second ary op erations. The bacteriology of graft sep sis has
changed . In 1977, Staphylococcus aureus w as the lead ing
pathogen (96), w ith a shift to S. epidermidis as the m ost
likely cau se of infection. S. epidermidis organism s are som e-
tim es d ifficu lt to culture from infected grafts. As su ch, p or- FIGURE 30.7. Infected graft in a redundant aortic aneurysm sac with visi-
tions of the grafts shou ld be finely d iced u p and cu ltu red ble gas bubbles (white arrow heads).
FIGURE 30.8. Bile staining (solid arrow) of an infected aortic graft as a

consequence of a duodenal erosion (open arrow). FIGURE 30.10. Infected aortic graft limb with opaque contrast injected
through an open sinus tract in the groin. Primary infection was an aortoduodenal
erosion.
Aortoenteric graft intestinal erosion is a d istinct su bcat- p lace. In this setting, the p roxim al lim b m ay be d ivid ed ,
egory of graft infection (Fig. 30.8). This com plication often soft tissu e interp osed betw een the lim b and the m ain bod y
follow s a lack of retrop eritoneal tissu e coverage of the of the graft, and the d istal lim b rem oved from the groin
imp lanted aortic graft d u ring the p rim ary reconstru ction after closu re of the abd om inal incision. If the bod y of an
(Fig. 30.9). Graft sep sis and intestinal bleed ing are u su ally aortic graft requ ires rem oval, the aortic stu m p m ust be
the first m anifestations of this com plication. The spread of securely closed w ith a d ou ble layer of m onofilam ent su tu re
the graft infection to involve the entire cond u it occu rs in and covered w ith om entu m or p resacral fascia.
m any cases (Fig. 30.10). In general, the entire prosthetic
graft in this setting m u st be excised . Structural Graft Failure
In the case of an isolated aortobifem oral graft lim b Serious stru ctural graft failu re is rare w ith m od ern grafts.
infection, after d emonstration of good incorp oration of the Most large p rostheses p laced in the aortoiliofem oral area
proxim al graft limb at the graft bifurcation, the limb alone fu nction w ell, exhibiting 85% to 95% long-term patencies.
m ay be rem oved leaving the remaind er of the graft in H ow ever, fabric p rostheses m ay exhibit friability, inability
A B
FIGURE 30.9. A: Endoscopy (black arrows denote exposed vascular graft). B: Confirming CTA, documenting an aortoenteric fistula
(white arrow head).
to hold su tu res, rents in the w all, aneu rysm form ation, and
both early and late d ilation (102). Defective grafts have
been d escribed for all types of grafts m onthly involving
Dacron knitted , w oven, and velour constru ction. Stru ctu ral
failu res in grafts u su ally reflect m echanical failu res in their
constru ction. Fabricated Dacron grafts, because of their
d esign, have been noted to increase in d iam eter by ap p rox-
im ately 15% to 20% follow ing insertion into the arterial cir-
culation. Anticip ated graft d ilation such as this m u st be
taken into consid eration w hen choosing a prosthetic graft
size for im p lantation.
Graft Thromboses
Early aortoiliac or aortofem oral graft throm boses are u su -
ally technical in nature, includ ing intim al flap s, anasto-
m otic narrow ing, graft tw isting or kinking, com pression of FIGURE 30.12. Intimal hyperplasia resulting in an anastomotic stenosis
(arrow) of an aortobifemoral bypass graft.
the graft lim b by the ingu inal ligam ent, unrecognized
inflow d isease, inad equ ate runoff becau se of u nap p reci-
ated d istal d isease, and u nd iagnosed hypercoagu lability
d isease, as op p osed to aneu rysm d isease, this relates to the
(103). Late graft throm boses are usu ally second ary to p ro-
p atency of the d eep fem oral artery. Progressive atheroscle-
gressive d ow nstream atherosclerosis or anastom otic inti-
rosis of the su perficial fem oral or infrap opliteal arteries
m al fibrod ysp lasia (Figs. 30.11 and 30.12).
m ay contribu te to graft throm bosis, p articu larly in patients
The m ost im p ortant factor contributing to long-term
w ho continu e to sm oke (103). Im p aired inflow is a m u ch
aortoiliac or aortofem oral graft patency is inad equ ate ou t-
less com m on cau se of late graft throm bosis (104), and w hen
flow. In the case of an aortofem oral bypass for occlu sive
it d oes occu r, it is m ost often associated w ith the low place-
m ent of grafts originating from the m ore term inal aorta.
Less frequ ent cau ses of late graft throm boses inclu d e kink-
ing or excessive angu lation of the graft lim bs, accum u la-
tion of m u ral throm bu s, and p seu d oaneu rysm formation.
A com p rehensive stu d y of 1,748 aortic reconstru ctions
in 1,647 p atients w ith aortoiliac occlu sive d isease inclu d ed
1,186 aortofem oral byp asses, 76 aortoiliac byp asses, 176
com bined aortoiliac and aortofem oral byp asses, 181 cases
of aortoiliac end arterectom y, and 129 rem ote byp asses
(105). Early p eriop erative or p ostop erative graft occlu sion
d ecreased from 8.3% from 1954 to 1963 to 3.2% from 1974
to 1983. Late anastom otic throm boses affected 13.1% of
aortofem oral byp asses, 10.5% of aortoiliac byp asses, 10.8%
of byp asses com bining aortoiliac and aortofem oral lim bs,
and 13.8% of aortoiliac end arterectom ies. Anastomotic
stenoses, defined as a reduction in lumen size to the degree of
the threatened thrombosis, occurred in 4.5% of aortofemoral
bypasses, 3.9% of aortoiliac bypasses, and 2.2% of aortoiliac
end arterectomies. Second ary repair of complications affect-
ing aortofemoral bypass procedures resulted in 77% 5-year
p atency rates, 77% 10-year p atency rates, 73% 15-year
patency rates, and 68% 20-year patency rates.
Anastomotic Aneurysms
Anastom otic aneu rysm s affect u p to 6% of all aortoiliac or
aortofem oral grafts (Fig. 30.13). In a large exp erience w ith
4,214 vascu lar reconstru ctions betw een 1957 and 1974,
there w as a 1.7% incid ence of anastom otic aneu rysm s,
occu rring w ith a 3% incid ence in the fem oral region, 1.2%
in the iliac region, and 0.2% in the aortic region (106). The
FIGURE 30.11. Late limb occlusion of an aortobifemoral bypass graft. m ost com m on cau se of false aneu rysm form ation w as the
FIGURE 30.13. Femoral artery anastomotic aneurysm

(arrow) affecting an aortobifemoral bypass graft limb.
stru ctu ral d eficiency of the host vessel, follow ed by Male Impotence
hyp ertension, m echanical stress, graft or su tu re d efects, Iatrogenic sexu al d ysfu nction, inclu d ing im p otence, and
and infection. Elective rep air of anastom otic aneu rysm s is retrograd e ejacu lation has been rep orted to range from 21%
su ccessfu l in 80% of cases, w hereas em ergency rep air is to 88% in m en u nd ergoing conventional aortic reconstru c-
su ccessfu l in 60% of cases. Late recu rrences range from tion. In a u niqu e exp erience em p loying a nerve-sparing
11% to 14%. ap p roach w ith m inim al aortic d issection and reperfusion
Fem oral false aneurysm s are u su ally obviou s on a phys- of at least one hyp ogastric vessel, im p otence w as elim i-
ical examination. If ru pture occurs, the vessel can u su ally nated and retrograd e ejacu lation w as red u ced from 43% to
be com p ressed p rior to em ergency op erative intervention. 3% (109). Inasm u ch as som e 70% to 80% of p atients w ith
H ow ever, aortic false aneurysm s m ay rem ain silent u ntil aortoiliac or aortofem oral arterial occlu sive d isease m ay
they becom e very large and ru p tu re w ith life-threatening alread y be im p otent, it is im p ortant to d ocu m ent the p res-
hem orrhage. Overall m ortality for treating anastom otic ence or absence of im p otence p rior to su rgery (110).
aneu rysms in the fem oral region is 3.5%, w ith an am p u ta- Vascu logenic im potence involves an inability to sustain
tion rate of 2.8% (107). Repair of false aortic aneu rysm s an erection (111). N eu rogenic im p otence refers to the
usu ally involves the insertion of a new segm ent of graft inability to achieve any erection at all. A p enile systolic–
after d ebrid em ent or excision of the involved native vessel. brachial ind ex below 0.6 is su p p ortive of the p resence of
End ovascu lar graft placem ent in this setting m ay prove vascu logenic im p otence. When vascu logenic im p otence
less hazard ou s (108). exists, consid eration shou ld be given to restoring internal
Table 3 0 .7 Com m on ea r ly a n d la te com plica t ion s ■ Early complications

follow in g lower ext r em it y byp a ss Myocardial Ischemia and Infarction
Early The major cause of early and late death after lower extremity
Myocardial infarction revascularization is myocardial infarction (118). Operative
Hemorrhage mortality rates between 3% and 5% accompany these proce-
Bypass graft thrombosis dures and are almost entirely due to perioperative cardiac
Lower extremity swelling (lymphocele, venous insufficiency) events. Patients treated for tibial or peroneal occlusive disease
Superficial skin infection (SSI) have a particularly high incidence of underlying coronary
Late artery disease that underlies these cardiac complications.
Graft thrombosis (neointimal hyperplasia 1–24 months, recurrent
atherosclerosis ( 24 months) Hemorrhage
Graft infection H em orrhage occu rs after low er extrem ity revascu lariza-
Retained AVfistula
tion in 1% to 3% of cases (119). Seriou s h em orrhage is
u su ally second ary to anastom otic bleed ing or u nligated
branches of im p lanted vein grafts. Less often, bleed ing is
iliac artery blood flow or occasionally performing a more d u e to coagu lation d efects, often related to the excessive
d irect revascu larization of the penis. In the presence of neu - ad m inistration of hep arin and the u se of d extran or
rogenic imp otence, a penile implant is acceptable treatment. antip latelet agents su ch as asp irin and Plavix.
Most patients d eveloping vasculogenic impotence from
aortic su rgery w ill not benefit from fu rther revascu lariza- Bypass Graft Thrombosis
tion, unless clear evid ence of impaired pelvic perfusion Acu te byp ass graft throm bosis occu rring w ithin 24 hou rs
exists. H ow ever, most w ill benefit from the new er pharm a- of su rgery affects ap p roximately 5% of low er extrem ity
cologic agents available to treat erectile d ysfunction. revascu larizations. The m ost com m on cau ses of early graft
throm boses are technical, inclu d ing inju ry to veins d u ring
harvest, intim al flap s from an incom p lete end arterectom y
■ LOWER EXTREMITY OCCLUSIVE DISEASE
or a clam p inju ry, im p rop er graft tu nneling cau sing tw isted
All patients w ho u nd ergo low er extrem ity revascu lariza- or kinked cond u its, and grafts p laced u nd er excessive ten-
tion shou ld be su bjected to rigorou s p ostop erative follow - sion. Early graft failu re is tw ice as com m on in bypass grafts
up (112). Su rveillance is consid ered m and atory to d etect p laced for lim b salvage com p ared to those u sed in treating
im p end ing graft failu re, w hich m ay occur in 50% of clau d ication (120). Poor arterial inflow and ou tflow have
patients. Sp ecific comp lications (Table 30.7) and com p lica- also been associated w ith early graft throm boses, as are
tion rates (Table 30.8) accom panying low er extrem ity infrap op liteal byp asses com p ared to above-the-knee
byp ass d eserve note (113–117). Althou gh low er extrem ity byp ass grafts. H yp ovolem ia or d im inished card iac ou tp ut
byp ass is com m only perform ed , large ad m inistrative d ata- can also contribu te to graft throm bosis. A hyp ercoagulable
bases su ggest that the overall m ortality for these p roce- state m ay affect ap p roxim ately 5% of p atients u nd ergoing
d u res is not insignificant (Table 30–9) (10,11). infraingu inal byp ass (121), and u nexp lained acu te graft
Table 3 0 .8 Com p lica t ion ra t es follow in g lower ext r em it y byp a ss from con t em p ora r y,
la r ge, sin gle in st it u t ion a l ser ies
Number of
Lower Extremity Myocardial Perioperative
Primary Year of Study Bypass Mortality Infarction Stroke Graft Failure Postoperative
Author Report Period Procedures (N) (%) (%) (%) (%) Bleeding (%)
Chew 2001 1983–1999 165a 1.8 9b Not stated 11 5.4
Goshima 2004 1990–2002 318 1.3 3.9 1.3 3.5 1.3
Pomposelli 2003 1990–2000 1,032c 1.0 3b 0.3 4.2 Not stated
Raffetto 2002 Not stated 352 1.1 2.6 0.3 6.8 0.8
Roddy 2003 1968–1999 5,880 3.1 2.9b Not stated 1.8d 2.1
a
Surgical technique using composite vein grafts only.
b
Percentage also reflects patients with other severe cardiac morbidity, such as congestive heart failure and arrhythmia.
c
Surgical technique using only the dorsalis pedis artery as the target vessel.
d
Perioperative graft failure defined as immediate limb loss.
Table 3 0 .9 Com p lica t ion ra t es from la r ge d a t a ba ses follow in g lower

ext r em it y byp a ss
Bypass
Primary Year of Study Procedures Mortality
Author Report Period (N) (%)
Aylin 2007 2001–2004 9,661 6.5%
a
Birkmeyer 2002 1994–1999 Approx. 250,000 4.9–6.1%
throm boses d eserve an evaluation for such. The u se of 24 m on th s after graft insertion are m ost often d u e to
statins m ay lessen low er extrem ity graft failu res (122,123). neointim al h yp erp lasia and are u su ally fou nd at the site
Most com p lication s affecting low er extrem ity revas- of th e d istal an astom osis (Figs. 30.14 an d 30.15). Graft
cu larizations are correctable if recognized early. In this occlu sion s that occu r beyond 24 m on th s are m ost often
regard , an objective assessm ent of the recon stru ction in d u e to the p rogression of atherosclerosis (126). In on e
the op eratin g room is critical. Com p letion angiograp h y stu d y, 87% of graft occlu sions second ary to the p rogres-
has been rep laced by intraop erative d u p lex exam ination sion of atherosclerosis occu rred beyond the first year of
as the m ost com m on m eans of assessing the ad equ acy of im p lantation (127).
graft p lacem ent (124), w ith stan d ard criteria p red ictive of
early byp ass graft failu re (117). Im m ed iate p ostop erative Graft Infection
ankle–brachial ind ices (ABIs) shou ld also be p erform ed Graft infection is a seriou s com p lication of low er extrem ity
to establish a baselin e by w h ich to com p are fu tu re ABI revascu larization. Mortality after low er extrem ity graft
stu d ies. infection averages 9% (128), and m ore than 50% of p atients
w ith this com p lication requ ire am p u tation. The incid ence
Lymphoceles and Lymph Drainage of graft infection is three tim es higher w hen u sing syn-
These complications occur most commonly follow ing groin thetic grafts com p ared to au togenou s vein grafts. The
d issection and usually result from lymphatic channel inter- overall incid ence of infection in exp and ed p olytetraflu o-
ruption or a transected lymph nod e. Lymphatic d rainage roethylene or Dacron grafts is ap p roxim ately 3% (128). If
through a surgical incision is usually treated initially w ith only one anastom osis is involved , local treatm ent w ith
strict bed rest and leg elevation. Frequent applications of antibiotics, w ou nd d ebrid em ent, and m u scle coverage
sterile dressings or povidone–iodine–soaked gauze to the m ay be attem p ted in selected cases. H ow ever, total graft
w ound lessens the incidence of w ound infection. Patients excision and revascu larization by an alternate rou te is
w ith small-volume intermittent drainage may be safely requ ired in m ost cases of infected synthetic cond u its.
managed nonoperatively for short periods by this method,
particularly in the absence of an und erlying prosthetic graft. Lower Extremity Edema
The need for operative intervention depends on the magni- Ed ema is a common and troublesome complication affect-
tude of the leak as w ell as the type of arterial reconstruction. ing as m any as tw o-third s of patients after low er extrem ity
Large quantities of lymph drainage or the presence of a pros- revascu larization (129,130). Three mechanisms contribute
thetic graft that w ould be at risk for infection necessitate to the d evelopment of ed ema. First, the loss of arteriolar
prompt surgical exploration, w ith id entification and ligature vasoconstriction d ue to chronic ischemia can lead to uncon-
of identifiable leaking lymphatics. trolled hyperemia and increased pressures w ithin the
microcirculation, particularly w hen the leg is d epend ent.
Large administrative datasets Second , interruption of lymphatic channels often occurs
Early com p lication rates d ocu m ented in large ad m inistra- d uring vascular d issection. Third , the harvesting of the ipsi-
tive d atabases are, for the m ost part, lacking for low er lateral greater saphenous vein as the cond u it for a byp ass
extrem ity byp asses, p erhap s, in part, d u e to the lack of hard may rend er some patients w ith w orsening venous insuffi-
end points that can be easily tracked . N evertheless, d ata ciency. Postoperative ed ema, althou gh often very obvious,
from these stu d ies d ocum ent a fairly high m ortality rate in is u su ally self-lim ited and resolves in 3 to 4 m onths. Com -
these p atients, fu rther confirm ing the systemic natu re of pression therapy in the form of su pport stockings or elastic
atherosclerosis. w raps m ay alleviate symptoms in these patients.
Complications of In Situ Saphenous Vein

■ Late complications Bypass Reconstructions
Late Graft Occlusion These includ e the persistence of large arteriovenous fistulas
Late (greater than 12 m onths) occlu sion of low er extrem - (Fig. 30.16), obstruction by residual valve leaflets, vasospasm,
ity revascu larization ap p ears as a resu lt of tw o d istinct and luminal platelet aggregation (131). Although small arte-
p athological entities (125). Those occu rring w ithin 12 to riovenou s fistu las are u su ally of little consequ ence, large
FIGURE 30.14. Femoral popliteal bypass stenosis due to intimal hyperplasia evident by duplex scan on direct image (arrow) and ele-
vated blood flow velocities.
FIGURE 30.15. Femoral artery to popliteal artery venous bypass stenosis

(arrow) evident on arteriogram. FIGURE 30.16. Retained vein graft fistula (arrow) following in situ vein bypass.
fistu las com m u nicating w ith the d eep system requ ire 14. Gu rm H S, Yad av JS, Fayad P, et al. Long-term resu lts of carotid stent-
ing versu s end arterectom y in high-risk p atients. N Engl J Med 2008;
interruption. Fistulas may be id entified by intraoperative 358(15):1572–1579.
Doppler examination or intraoperative arteriography. Their 15. Stanley JC, Barnes RW, Ernst CB, et al. Vascu lar su rgery in the United
late persistence often causes areas of cutaneous erythema States: w orkforce issu es. Rep ort of the Society for Vascu lar Su rgery
and the International Society for Card iovascu lar Su rgery, N orth
and painful induration. Residual competent valve leaflets Am erican Chap ter, Com m ittee on Workforce Issu es. J Vasc Surg 1996;
are a recognized cause of early graft thrombosis when the 23(1):172–181.
retrograde passing of a valvulotome or valve cutter com- 16. Moore WS, Barnett H J, Beebe H G, et al. Gu id elines for carotid
end arterectom y. A m u ltid iscip linary consensu s statem ent from the
presses the valve leaflet against the vein wall, where it Ad H oc Com m ittee, Am erican H eart Association. Circulation 1995;
snpaily remains in the open position. Id entification of these 91(2):566–579.
collapsed leaflets on intraoperative angiography is d ifficult. 17. Biller J, Feinberg WM, Castald o JE, et al. Gu id elines for carotid
end arterectom y: a statem ent for healthcare professionals from a Spe-
Sometimes only direct mechanical manipulation of the vein cial Writing Group of the Stroke Cou ncil, Am erican H eart Associa-
w ill cause the leaflet to go into the closed position, allow ing tion. Circulation 1998;97(5):501–509.
id entification. Platelet aggregates invariably attach to the 18. Cow an JA Jr, Dim ick JB, Thom p son BG, et al. Su rgeon volu m e as an
ind icator of outcom es after carotid end arterectom y: an effect ind e-
damaged end othelium from mechanical or ischemic injury p end ent of sp ecialty p ractice and hosp ital volu m e. J Am Coll Surg
and may, on occasion, require a longitudinal venotomy for 2002;195(6):814–821.
removal, follow ed by vein patch angioplasty to close the 19. Ballotta E, Da Giau G, Piccoli A, et al. Du rability of carotid end arterec-
tom y for treatm ent of sym p tom atic and asym p tom atic stenoses. J Vasc
defect. Attempts at platelet removal by balloon catheter in Surg 2004;40(2):270–278.
this setting may only cause further vein injury and platelet 20. Conrad MF, Shep ard AD, Pand u rangi K, et al. Ou tcom e of carotid
aggregation (131). end arterectom y in African Am ericans: is race a factor? J Vasc Surg
2003;38(1):129–137.
21. Darling RC III, Mehta M, Rod d y SP, et al. Eversion carotid end arterec-
tom y: a technical alternative that m ay obviate patch closure in
■ REFERENCES w om en. Cardiovasc Surg 2003;11(5):347–352.
22. Ecker RD, Pichelm ann MA, Meissner I, et al. Du rability of carotid
1. Upchurch GR, Dim ick JB, Wainess RM, et al. Diffu sion of new tech- end arterectom y. Stroke 2003;34(12):2941–2944.
nology in health care: the case of aorto-iliac occlu sive d isease. Surgery 23. Illig KA, Shortell CK, Zhang R, et al. Carotid end arterectom y then and
2004;136(4):812–818. now : ou tcom e and cost-effectiveness of m od ern p ractice. Surgery
2. McPhee JT, Schanzer A, Messina LM, et al. Carotid artery stenting has 2003;134(4):705–711, d iscussion 711–712.
increased rates of postp roced u re stroke, d eath, and resou rce u tiliza- 24. Debakey ME, Craw ford ES, Cooley DA, et al. Cerebral arterial insu ffi-
tion than d oes carotid end arterectom y in the United States, 2005. ciency: one to 11-year results follow ing arterial reconstru ctive op era-
J Vasc Surg 2008;48(6):1442–1450, 1450.e1. tion. Ann Surg 1965;161:921–945.
3. Sid aw y AN , Zw olak RM, White RA, et al. Risk-ad ju sted 30-d ay ou t- 25. H ertzer N R, Arison R. Cu m u lative stroke and su rvival ten years after
com es of carotid stenting and end arterectom y: resu lts from the SVS carotid end arterectom y. J Vasc Surg 1985;2(5):661–668.
Vascular Registry. J Vasc Surg 2009;49(1):71–79. 26. Perler BA, Bu rd ick JF, William s GM. The safety of carotid end arterec-
4. H alm EA, Tu hrim S, Wang JJ, et al. Racial and ethnic d isp arities in ou t- tom y at the tim e of coronary artery byp ass su rgery: analysis of resu lts
com es and app ropriateness of carotid end arterectom y: im p act of in a high-risk p atient pop u lation. J Vasc Surg 1985;2(4):558–563.
p atient and provid er factors. Stroke 2009;40(7):2493–2501. 27. H ertzer N R, Loop FD, Beven EG, et al. Su rgical staging for sim u ltane-
5. Vogel TR, Dom brovskiy VY, H aser PB, et al. Ou tcom es of carotid ou s coronary and carotid d isease: a stu d y includ ing prospective ran-
artery stenting and end arterectom y in the United States. J Vasc Surg d om ization. J Vasc Surg 1989;9(3):455–463.
2009;49(2):325–330, d iscu ssion 330. 28. Ricotta JJ, Peterson, MJ, Char DJ, Cu rrent therap y in vascu lar su rgery.
6. Dillavou ED, Mu lu k SC, Makarou n MS. A d ecad e of change in In: Ernst CB, Stanley JC. ed s. Management of concomitant carotid and
abd om inal aortic aneu rysm rep air in the United States: H ave w e coronary arterial disease. St. Lou is, MO: Mosby; 2001:101–104.
im p roved ou tcom es equ ally betw een m en and w om en? J Vasc Surg 29. Brow n KR, Kresow ik TF, Chin MH , et al. Mu ltistate p op u lation-based
2006;43(2):230–238, d iscu ssion 238. ou tcom es of com bined carotid end arterectom y and coronary artery
7. Giles KA, Scherm erhorn ML, O’Malley AJ, et al. Risk p red iction for bypass. J Vasc Surg 2003;37(1):32–39.
p erioperative m ortality of end ovascu lar vs op en rep air of abd om inal 30. Graham AM, Gew ertz BL, Zarins CK. Pred icting cerebral ischem ia
aortic aneurysms using the Medicare population. J Vasc Surg 2009;50(2): d u ring carotid end arterectom y. Arch Surg 1986;121(5):595–598.
256–262. 31. Till JS, Toole JF, H ow ard VJ, et al. Declining m orbid ity and m ortality
8. Scherm erhorn ML, O’Malley AJ, Jhaveri A, et al. End ovascular vs. of carotid end arterectom y. The Wake Forest University Med ical Cen-
op en repair of abd om inal aortic aneu rysm s in the Med icare popula- ter exp erience. Stroke 1987;18(5):823–829.
tion. N Engl J Med 2008;358(5):464–474. 32. Im p arato AM, Riles TS, Lam p arello PJ, et al. Com p lications in vascu -
9. Schw arze ML, Shen Y, H em m erich J, et al. Age-related trend s in u ti- lar su rgery. In: Bernhard VM, Tow ne JB, ed s. The management of TIA
lization and outcom e of op en and end ovascu lar rep air for abd om inal and acute strokes after carotid endarterectomy. N ew York, N Y: Gru ne &
aortic aneu rysm in the United States, 2001–2006. J Vasc Surg 2009; Stratton; 1985:725.
50(4):722–729.e2. 33. Moore WS, H all AD. Carotid artery back p ressu re: a test of cerebral tol-
10. Aylin P, Lees T, Baker S, et al. Descrip tive stu d y com p aring rou tine erance to tem porary carotid occlusion. Arch Surg 1969;99(6):702–710.
hospital ad m inistrative d ata w ith the Vascular Society of Great Britain 34. H ays RJ, Levinson SA, Wylie EJ. Intraop erative m easu rem ent of
and Ireland ’s N ational Vascu lar Database. Eur J Vasc Endovasc Surg carotid back p ressu re as a gu id e to op erative m anagem ent for carotid
2007;33(4):461–465, d iscu ssion 466. end arterectom y. Surgery 1972;72(6):953–960.
11. Birkm eyer JD, Siew ers AE, Finlayson EV, et al. H osp ital volu m e and 35. Kw aan JH , Peterson GJ, Connolly JE. Stu m p p ressu re: an u nreliable
su rgical m ortality in the United States. N Engl J Med 2002;346(15): gu id e for shunting d u ring carotid end arterectom y. Arch Surg 1980;
1128–1137. 115(9):1083–1086.
12. Stanley JC, Messina LM, Wakefield TW. Com p lications in su rgery and 36. Baker JD, Gluecklich B, Watson CW, et al. An evalu ation of electroen-
trau m a. In: Greenfield LJ, ed s. Complications in vascular surgery and cephalograp hic m onitoring for carotid stu d y. Surgery 1975;78(6):
trauma. Philad elphia, PA: JB Lip p incott; 1989:359–387. 787–794.
13. H ow ard VJ, Voeks JH , Lu tsep H L, et al. Does sex m atter? Thirty- 37. Pruitt JC. 1009 consecu tive carotid end arterectom ies u sing local anes-
d ay stroke and d eath rates after carotid artery stenting in w om en thesia, EEG, and selective shu nting w ith Pru itt-Inahara carotid shu nt.
versu s m en: resu lts from th e Carotid Revascu larization En d arterec- Contemp Surg 1983;23:49–58.
tom y versu s Stenting Trial (CREST) lead -in p hase. Stroke 2009;40(4): 38. Brooke BS, McGirt MJ, Wood w orth GF, et al. Preop erative statin and
1140–1147. d iu retic u se influ ence the p resentation of p atients u nd ergoing carotid
end arterectom y: results of a large single-institution case-control 65. H ertzer N R. Fatal m yocard ial infarction follow ing abd om inal aortic
stu d y. J Vasc Surg 2007;45(2):298–303. aneu rysm resection . Th ree hu n d red forty-th ree p atients follow ed
39. Ascher E, Markevich N , Kallaku ri S, et al. Intraop erative carotid 6–11 years postop eratively. Ann Surg 1980;192(5):667–673.
artery d uplex scanning in a m od ern series of 650 consecu tive p rim ary 66. Beven EG. Rou tine coronary angiograp hy in p atients u nd ergoing su r-
end arterectom y p roced u res. J Vasc Surg 2004;39(2):416–420. gery for abd om inal aortic aneu rysm and low er extrem ity occlu sive
40. Cap lan LR, Skillm an J, Ojem ann R, et al. Intracerebral hem orrhage d isease. J Vasc Surg 1986;3(4):682–684.
follow ing carotid end arterectom y: a hypertensive com plication? 67. Froehlich JB, Karavite D, Ru ssm an PL, et al. Am erican College of Car-
Stroke 1978;9(5):457–460. d iology/ Am erican H eart Association p reop erative assessm ent gu id e-
41. Mou lakakis KG, Mylonas SN , Sfyroeras GS, et al. H yperp erfu sion lines red uce resou rce u tilization before aortic su rgery. J Vasc Surg
synd rom e after carotid revascu larization. J Vasc Surg 2009;49(4): 2002;36(4):758–763.
1060–1068. 68. Eagle KA, Bru nd age BH , Chaitm an BR, et al. Gu id elines for p eriop er-
42. H ertzer N R. Vascu lar su rgery. In: Ru therford RB, ed . Postoperative ative card iovascular evalu ation for noncard iac su rgery. Rep ort of the
management and complications of extracranial carotid reconstruction. Am erican College of Card iology/ Am erican H eart Association Task
Philad elphia, PA: W.B. Sau nd ers; 1984:1300. Force on p ractice guid elines (com m ittee on perioperative card iovas-
43. Evans WE, Mend elow itz DS, Liap is C, et al. Motor sp eech d eficit fol- cular evalu ation for noncard iac su rgery). J Am Coll Cardiol 1996;27(4):
low ing carotid end arterectom y. Ann Surg 1982;196(4):461–464. 910–948.
44. Thom pson JE. Com p lications of carotid end arterectom y and their p re- 69. Ohu chi H , Gojo S, Sato H , et al. Sim u ltaneou s abd om inal aortic
vention. World J Surg 1979;3(2):155–165. aneu rysm rep air d u ring the on-pum p coronary artery byp ass graft-
45. Bove EL, Fry WJ, Gross WS, et al. H yp otension and hyp ertension as ing. Ann Thorac Cardiovasc Surg 2003;9(6):409–411.
consequ ences of barorecep tor d ysfu nction follow ing carotid 70. H ertzer N R, You ng JR, Beven EG, et al. Late resu lts of coronary
end arterectom y. Surgery 1979;85(6):633–637. bypass in patients w ith infrarenal aortic aneu rysm s. The Cleveland
46. Posner SR, Boxer L, Proctor M, et al. Uncom p licated carotid Clinic Stud y. Ann Surg 1987;205(4):360–367.
end arterectom y: factors contribu ting to blood pressu re instability pre- 71. Diehl JT, Cali RF, H ertzer N R, et al. Com p lications of abd om inal aortic
clu d ing safe early d ischarge. Vascular 2004;12(5):278–284. reconstru ction. An analysis of p eriop erative risk factors in 557
47. Wad e JG, Larson CP Jr, H ickey RF, et al. Effect of carotid end arterec- patients. Ann Surg 1983;197(1):49–56.
tom y on carotid chem orecep tor and barorecep tor fu nction in m an. N 72. O’H ara PJ, H ertzer N R, Santilli PH , et al. Intraop erative au totransfu -
Engl J Med 1970;282(15):823–829. sion d u ring abd om inal aortic reconstru ction. Am J Surg 1983;145(2):
48. Clagett GP, Rich N M, McDonald PT, et al. Etiologic factors for recu r- 215–220.
rent carotid artery stenosis. Surgery 1983;93(2):313–318. 73. Clagett GP, Valentine RJ, Jackson MR, et al. A rand om ized trial of
49. Stoney RJ, String ST. Recu rrent carotid stenosis. Surgery 1976;80(6): intraop erative au totransfu sion d u ring aortic su rgery. J Vasc Surg
705–710. 1999;29(1):22–30, d iscu ssion 30–31.
50. Im p arato AM, Bracco A, Kim GE, et al. Intim al and neointim al fibrou s 74. H aim ovici H . Vascular em ergencies. In: H aim ovici H , ed . Metabolic
p roliferation causing failu re of arterial reconstru ctions. Surgery 1972; syndrome secondary to acute arterial occlusions. East N orw alk, CT:
72(6):1007–1017. Ap p leton & Lange; 1982:267.
51. Rapp J, Stoney RJ, Com p lications in vascu lar su rgery. In: Bernhard 75. Bush H L Jr. Renal failu re follow ing abd om inal aortic reconstru ction.
VM, Tow ne JB, ed s. Recurrent carotid stenosis. N ew York, N Y: Gru ne & Surgery 1983;93(1 Pt 1):107–109.
Stratton; 1986:767. 76. Wakefield TW, Whitehou se WM Jr, Wu SC, et al. Abd om inal aortic
52. Archie JP Jr. A fifteen-year exp erience w ith carotid end arterectom y aneurysm ru ptu re: statistical analysis of factors affecting ou tcom e of
after a form al op erative p rotocol requ iring highly frequent p atch su rgical treatm ent. Surgery 1982;91(5):586–596.
angioplasty. J Vasc Surg 2000;31(4):724–735. 77. H assoun H T, Miller CC III, H u ynh TT, et al. Cold visceral p erfu sion
53. Rod d y SP, Darling RC III, Ozsvath KJ, et al. Choice of m aterial for im proves early survival in patients w ith acu te renal failu re after tho-
internal carotid artery byp ass grafting: vein or p rosthetic? Analysis of racoabd om inal aortic aneu rysm rep air. J Vasc Surg 2004;39(3):506–512.
44 proced ures. Cardiovasc Surg 2002;10(6):540–544. 78. Craw ford ES, Craw ford JL, Safi H J, et al. Thoracoabd om inal aortic
54. Attigah N , Kulkens S, Deyle C, et al. Red o Su rgery or Carotid Stenting aneu rysm s: p reop erative and intraoperative factors d eterm ining
for Restenosis after Carotid End arterectom y: Resu lts of Tw o Different im m ed iate and long-term resu lts of op erations in 605 p atients. J Vasc
Treatm ent Strategies. Ann Vasc Surg 2009;24(2):190–195. Surg 1986;3(3):389–404.
55. Reu l GJ, Cooley DA. Reop erative arterial su rgery. In: Bergan JJ, Yao 79. Starr DS, Law rie GM, Morris GC Jr. Prevention of d istal em bolism
JST, ed s. False aneurysm of the carotid artery. N ew York, N Y: Grune & d u ring arterial reconstru ction. Am J Surg 1979;138(6):764–769.
Stratton; 1986:538. 80. Crow son M, Field ing JW, Black J, et al. Acu te gastrointestinal com p li-
56. Dim ick JB, Stanley JC, Axelrod DA, et al. Variation in d eath rate after cations of infrarenal aortic aneu rysm rep air. Br J Surg 1984;71(11):
abd om inal aortic aneu rysm ectom y in the United States: im p act of 825–828.
hosp ital volum e, gend er, and age. Ann Surg 2002;235(4):579–585. 81. Zelenock GB, Strod el WE, Knol JA, et al. A p rosp ective stu d y of clini-
57. Dim ick JB, Up chu rch GR Jr. The qu ality of care for p atients w ith cally and end oscopically d ocu m ented colonic ischem ia in 100 p atients
abd om inal aortic aneu rysm s. Cardiovasc Surg 2003;11(5):331–336. und ergoing aortic reconstru ctive su rgery w ith aggressive colonic and
58. Katz DJ, Stanley JC, Zelenock GB. Op erative m ortality rates for intact d irect p elvic revascu larization, com p ared w ith historic controls.
and ru p tu red abd om inal aortic aneu rysm s in Michigan: an eleven- Surgery 1989;106(4):771–779, d iscu ssion 779–780.
year statew id e exp erience. J Vasc Surg 1994;19(5):804–815, d iscu ssion 82. H agihara PF, Ernst CB, Griffen WO Jr. Incid ence of ischem ic colitis
816–817. follow ing abd om inal aortic reconstru ction. Surg Gynecol Obstet 1979;
59. Katz DJ, Stanley JC, Zelenock GB. Gend er d ifferences in abd om inal 149(4):571–573.
aortic aneu rysm p revalence, treatm ent, and ou tcom e. J Vasc Surg 1997; 83. Ernst CB, H agihara PF, Dau gherty ME, et al. Inferior m esenteric
25(3):561–568. artery stu m p p ressure: a reliable ind ex for safe IMA ligation d u ring
60. Bertges DJ, Rhee RY, Mu lu k SC, et al. Is rou tine u se of the intensive abd om inal aortic aneurysm ectom y. Ann Surg 1978;187(6):641–646.
care u nit after elective infrarenal abd om inal aortic aneurysm repair 84. Mitchell KM, Valentine RJ. Inferior m esenteric artery reim p lantation
necessary? J Vasc Surg 2000;32(4):634–642. d oes not gu arantee colon viability in aortic su rgery. J Am Coll Surg
61. Elkou ri S, Gloviczki P, McKu sick MA, et al. Periop erative com p lica- 2002;194(2):151–155.
tions and early ou tcom e after end ovascu lar and op en su rgical rep air 85. Szilagyi DE, H agem an JH , Sm ith RF, et al. Sp inal cord d am age in su r-
of abd om inal aortic aneu rysm s. J Vasc Surg 2004;39(3):497–505. gery of the abd om inal aorta. Surgery 1978;83(1):38–56.
62. H ertzer N R, Mascha EJ, Karafa MT, et al. Op en infrarenal abd om inal 86. Elliott JP, Szilagyi DL, H agem an JH , et al, Com p lications in vascu lar
aortic aneurysm rep air: the Cleveland Clinic exp erience from 1989 to su rgery. In: Bernhard VM, Tow ne JB, ed s. Spinal cord ischemia: second-
1998. J Vasc Surg 2002;35(6):1145–1154. ary to surgery of the abdominal aorta. N ew York, N Y: Gru ne & Stratton;
63. Menard MT, Chew DK, Chan RK, et al. Ou tcom e in p atients at high 1985:291.
risk after open su rgical rep air of abd om inal aortic aneu rysm . J Vasc 87. Picone AL, Green RM, Ricotta JR, et al. Sp inal cord ischem ia follow ing
Surg 2003;37(2):285–292. operations on the abd om inal aorta. J Vasc Surg 1986;3(1):94–103.
64. Dau chot PJ, DePalm a R, Gru m D, et al. Detection and prevention of 88. McCu llough JL, H ollier LH , N u gent M. Parap legia after thoracic aor-
card iac d ysfunction d u ring aortic su rgery. J Surg Res 1979;26(5): tic occlu sion: influ ence of cerebrosp inal flu id d rainage. Exp erim ental
574–580. and early clinical resu lts. J Vasc Surg 1988;7(1):153–160.
89. Acher CW, Wynn MM, H och JR, et al. Com bined u se of cerebral sp inal 111. DePalm a RG, Em sellem H A, Ed w ard s CM, et al. A screening
flu id d rainage and naloxone red u ces the risk of p arap legia in thora- sequ ence for vascu logenic im p otence. J Vasc Surg 1987;5(2):228–236.
coabd om inal aneu rysm rep air. J Vasc Surg 1994;19(2):236–246, d iscus- 112. Ferris BL, Mills JL Sr, H u ghes JD, et al. Is early p ostop erative d u p lex
sion 247–248. scan su rveillance of leg byp ass grafts clinically im p ortant? J Vasc Surg
90. Laschinger JC, Cunningham JN Jr, Catinella FP, et al. Detection and 2003;37(3):495–500.
prevention of intraop erative sp inal cord ischem ia after cross-clam p - 113. Chew DK, Conte MS, Donald son MC, et al. Au togenou s com p osite
ing of the thoracic aorta: use of som atosensory evoked potentials. vein byp ass graft for infraingu inal arterial reconstru ction. J Vasc Surg
Surgery 1982;92(6):1109–1117. 2001;33(2):259–264, d iscussion 264–265.
91. Joob AW, Dunn C, Miller E, et al. Effect of left atrial to left fem oral 114. Goshim a KR, Mills JL Sr, H u ghes JD. A new look at ou tcom es after
artery bypass and renin-angiotensin system blockad e on renal blood infrainguinal bypass su rgery: trad itional rep orting stand ard s system -
flow and fu nction d u ring and after thoracic aortic occlu sion. J Vasc atically u nd erestim ate the expend itu re of effort required to attain
Surg 1987;5(2):329–335. lim b salvage. J Vasc Surg 2004;39(2):330–335.
92. Labard ini MM, Ratliff RK. The abd om inal aortic aneu rysm and the 115. Pom poselli FB, Kansal N , H am d an AD, et al. A d ecad e of exp erience
u reter. J Urol 1967;98(5):590–596. w ith d orsalis ped is artery bypass: analysis of ou tcom e in m ore than
93. Szilagyi DE, Sm ith RF, Elliott JP, et al. Infection in arterial reconstruc- 1000 cases. J Vasc Surg 2003;37(2):307–315.
tion w ith synthetic grafts. Ann Surg 1972;176(3):321–333. 116. Raffetto JD, Chen MN , LaMorte WW, et al. Factors that p red ict site of
94. Reilly LM, Altm an H , Lu sby RJ, et al. Late resu lts follow ing su rgical ou tflow target artery anastom osis in infraingu inal revascu larization.
m anagem ent of vascu lar graft infection. J Vasc Surg 1984;1(1):36–44. J Vasc Surg 2002;35(6):1093–1099.
95. Macbeth GA, Rubin JR, McIntyre KE Jr, et al. The relevance of arterial 117. Rod d y SP, Darling RC III, Maharaj D, et al. Gend er-related d ifferences
w all m icrobiology to the treatm ent of p rosthetic graft infections: graft in ou tcom e: an analysis of 5880 infraingu inal arterial reconstru ctions.
infection vs. arterial infection. J Vasc Surg 1984;1(6):750–756. J Vasc Surg 2003;37(2):399–402.
96. Liekw eg WG Jr, Greenfield LJ. Vascu lar p rosthetic in fections: col- 118. H ertzer N R. Fatal m yocard ial infarction follow ing low er extrem ity
lected exp erien ce an d resu lts of treatm en t. Surgery 1977;81(3): revascu larization. Tw o hu nd red seventy-three p atients follow ed six
335–342. to eleven p ostop erative years. Ann Surg 1981;193(4):492–498.
97. Tollefson DF, Band yk DF, Kaebnick H W, et al. Su rface biofilm d isru p- 119. Brew ster DC. Com p lications in vascu lar su rgery. In: Bernhard VM,
tion. Enhanced recovery of m icroorganism s from vascu lar p rostheses. Tow ne JB, ed . Early complications of vascular repair below the inguinal lig-
Arch Surg 1987;122(1):38–43. ament. N ew York, N Y: Gru ne & Stratton; 1985:37.
98. Reilly LM, Stoney RJ, Gold stone J, et al. Im p roved m anagem ent of 120. Brew ster DC, LaSalle AJ, Robison JG, et al. Fem orop op liteal graft fail-
aortic graft infection: the influ ence of op eration sequ ence and staging. ures. Clinical consequ ences and su ccess of second ary reconstru ctions.
J Vasc Surg 1987;5(3):421–431. Arch Surg 1983;118(9):1043–1047.
99. Clagett GP, Valen tin e RJ, H agin o RT. Au togen ou s aortoiliac/ 121. Donald son MC, Mannick JA, Whittem ore AD. Cau ses of p rim ary
fem oral reconstru ction from su p erficial fem oral-p op liteal veins: fea- graft failu re after in situ sap henou s vein byp ass grafting. J Vasc Surg
sibility and d u rability. J Vasc Surg 1997;25(2):255–266, d iscu ssion 1992;15(1):113–138, d iscu ssion 118–120.
267–270. 122. H enke PK, Blackbu rn S, Proctor MC, et al. Patients u nd ergoing
100. Kieffer E, Gom es D, Chiche L, et al. Allograft rep lacem ent for infrainguinal bypass to treat atherosclerotic vascu lar d isease are
infrarenal aortic graft infection: early and late resu lts in 179 p atients. und erp rescribed card iop rotective m ed ications: effect on graft
J Vasc Surg 2004;39(5):1009–1017. patency, lim b salvage, and m ortality. J Vasc Surg 2004;39(2):357–365.
101. Band yk DF, N ovotney ML, Johnson BL, et al. Use of rifam p in-soaked 123. Abbru zzese TA, H avens J, Belkin M, et al. Statin therap y is associated
gelatin-sealed p olyester grafts for in situ treatm ent of p rim ary aortic w ith im p roved patency of au togenou s infraingu inal byp ass grafts.
and vascular p rosthetic infections. J Surg Res 2001;95(1):44–49. J Vasc Surg 2004;39(6):1178–1185.
102. Stanley JC, Lind enau er SM, Graham LM, et al. Vascu lar su rgery. A 124. Band yk DF. Reop erative arterial su rgery. In: Bergan JJ, Yao JST, ed .
com prehensive review. In: Moore W, ed s. Vascular grafts. N ew York, Postoperative surveillance of femorodistal grafts: the application of echo-
N Y: Gru ne & Stratton; 1986:365–390. Doppler (duplex) ultrasonic scanning. N ew York, N Y: Gru ne & Stratton;
103. Lalka SG, Bernhard VM. Vascu lar su rgery. A com p rehensive review. 1986:59.
In: Moore W, ed s. Noninfectious complications in vascular surgery. N ew 125. LoGerfo FW, Qu ist WC, Cantelm o N L, et al. Integrity of vein grafts as
York, N Y: Grune & Stratton; 1986:959. a fu nction of initial intim al and m ed ial p reservation. Circulation 1983;
104. Brew ster DC, Darling RC. Op tim al m ethod s of aortoiliac reconstru c- 68(3 Pt 2):II117–II124.
tion. Surgery 1978;84(6):739–748. 126. Veith FJ, Gu p ta S, Daly V. Managem ent of early and late throm bosis of
105. Szilagyi DE, Elliott JP Jr, Sm ith RF, et al. A thirty-year su rvey of the expand ed polytetraflu oroethylene (PTFE) fem oropopliteal bypass
reconstructive su rgical treatm ent of aortoiliac occlu sive d isease. J Vasc grafts: favorable p rognosis w ith ap p rop riate reop eration. Surgery
Surg 1986;3(3):421–436. 1980;87(5):581–587.
106. Szilagyi DE, Sm ith RF, Elliott JP, et al. Anastom otic aneu rysm s after 127. Wh ittem ore AD, Clow es AW, Cou ch N P, et al. Second ary
vascu lar reconstru ction: p roblem s of incid ence, etiology, and treat- fem orop op liteal reconstru ction. Ann Surg 1981;193(1):35–42.
m ent. Surgery 1975;78(6):800–816. 128. Du rham JR, Ru bin JR, Malone JM. Reop erative arterial su rgery. In:
107. Evans WE, Mend elow itz DS, Liap is C, et al. Com p lications in vascu lar Bergan JJ, Yao JST, ed s. Management of infected infrainguinal bypass
su rgery. In: Bernhard VM, Tow ne JB, ed s. Anastomotic femoral false grafts. N ew York, N Y: Grune & Stratton; 1986:359.
aneurysms. N ew York, N Y: Gru ne & Stratton; 1985:205. 129. Schu bart PJ, Porter JM. Reop erative arterial su rgery. In: Bergan JJ, Yao
108. Berchtold C, Eibl C, Seelig MH , et al. End ovascu lar treatm ent and JST, ed s. Leg edema following femorodistal bypass. N ew York, N Y: Gru ne
com plete regression of an infected abd om inal aortic aneu rysm . & Stratton; 1986:331.
J Endovasc Ther 2002;9(4):543–548. 130. Eickhoff JH , Engell H C. Local regu lation of blood flow and the occu r-
109. Flanigan DP, Schu ler JJ, Keifer T, et al. Elim ination of iatrogenic im p o- rence of ed em a after arterial reconstru ction of the low er lim bs. Ann
tence and im p rovem ent of sexu al fu nction after aortoiliac revascu lar- Surg 1982;195(4):474–478.
ization. Arch Surg 1982;117(5):544–550. 131. Leather RP, Karmody AM, Shah DM, et al. Reoperative arterial surgery.
110. N ath RL, Menzoian JO, Kap lan KH , et al. The m u ltid iscip linary In: Bergan JJ, Yao JST, ed s. The in situ saphenous vein arterial bypass. N ew
ap proach to vascu logenic im p otence. Surgery 1981;89(1):124–133. York, N Y: Grune & Stratton; 1986:299.
CHAPTER
31
Complications of Venous
Disease and Therapy
Thomas W. Wakefield and Peter K. Henke
■ INCIDENCE, RISK FACTORS, AND CATEGORIES inclu d e u nilateral lim b p ain and sw elling, bu t DVT is
som etim es silent, w ith PE as the first m anifestation.
Deep venou s throm bosis (DVT) and p u lm onary em bolism
(PE), together called venous throm boem bolism (VTE), are
a seriou s health concern. It has been estimated that there ■ Phlegmasia alba dolens/phlegmasia
are m ore than 900,000 cases per year in the US (1). Ap p rox- cerulea dolens
im ately 300,000 p eople d ie of PE yearly and d eaths from PE Massive iliofem oral DVT m ay cau se p hlegm asia alba
are five tim es m ore com m on than d eaths from breast can- d olens (the w hite sw ollen leg) and p hlegm asia ceru lea
cer, AIDS, and m otor vehicle accid ents com bined . VTE is d olens (the blu e sw ollen leg). When cap illaries occlu d e,
the third m ost com m on vascu lar d isease after heart d is- venou s gangrene m ay resu lt, as arterial inflow becom es
ease and stroke. In ad d ition, p atients w ith p ain and leg obstru cted d u e to extrem e venou s hyp ertension. Alterna-
sw elling after throm bosis (called postthrombotic syndrome tively, arterial em boli or sp asm m ay occu r. The toes on the
[PTS]) su ffer p oor qu ality of life d u e to chronic sym p tom s. involved lim b tu rn blu e and black, and the skin blisters.
PTS occu rs in as m any as 30% of p atients ovserved over Venou s gangrene can be d ifferentiated from arterial
8 years (2). ischem ia by generalized sw elling and lim b blu eness as
Acquired risk factors include age, malignancy, surgery, op p osed to the p ale, cold limb of acu te arterial ischem ia.
trauma, immobilization, oral contraceptive use, hormone Venou s gangrene is often associated w ith an u nd erlying
replacement therapy, pregnancy and the puerperium, obe- m alignancy, and p hlegm asia ceru lea d olens virtually
sity, neurological disease, cardiac disease, and antiphospho- alw ays p reced es this d iagnosis. Am p u tation rates of 20% to
lipid antibodies (3). Genetic risk factors includ e d eficiencies 50% are noted , w ith PE rates of 12% to 40% and m ortality of
of antithrombin, protein C and protein S, factor V Leiden, 20% to 40% (6).
prothrombin 20210 A, blood group non-O, hyperhomocys-
teinemia, dysfibrinogenemia, dysplasminogenemia, reduced
heparin cofactor II activity, elevated levels of clotting factors ■ Axillary/subclavian vein thrombosis
(factors XI, IX, VII, VIII, X, and II), and plasminogen activator
inhibitor-1 (4). Hematologic diseases associated with an Throm bosis of the axillary/ su bclavian vein is an u ncom -
increased risk of DVT include d isseminated intravascular m on event accou nting for 5% of all cases of acu te DVT.
coagulation, heparin-induced thrombocytopenia (HIT), N evertheless, axillary/ su bclavian venou s throm boses
thrombotic thrombocytopenic purpura (TTP), antiphospho- have been associated w ith PE in u p to 10% to 15% of cases
lipid antibod y syndrome, hemolytic uremic syndrome, and and can be the sou rce of significant d isability (7). Prim ary
myeloproliferative disorders (polycythemia vera and essen- axillary/ su bclavian vein throm bosis resu lts from inter-
tial thrombocythemia) (5). m ittent obstru ction of the vein in the thoracic ou tlet
Wh en a p atien t p resents w ith an u np rovoked VTE at (Paget—von Schrötter synd rom e) in relatively healthy
a you ng age (age 50 years), unu sual site of throm bosis m u scu lar ind ivid u als, w ith strenu ou s exercise often p re-
(e.g., m esenteric veins), or if there is a fam ily history of cipitating the thrombosis. Thrombosis may also occur in
VTE, a w ork-u p for a hypercoagulable state is su ggested p atients w ith hyp ercoagu lable states. Second ary axillary/
(Table 31.1) (3,4). subclavian vein throm bosis m ost com m only resu lts from
Most cases of DVT affect the low er lim b and inclu d e ind w elling catheters or p acem aker w ires. Less com m on
the p op liteal, fem oral, or iliac veins. Presenting sym p tom s secondary causes include congestive heart failure, nephrotic
synd rom e, m ed iastinal tu m ors, and m alignancy. Most
p atients present with pain, ed ema, and cyanosis of the arm.
Superficial venous distension may be apparent in the arm,
Thomas W. Wakefield and Peter K. Henke: Section of Vas- forearm, shoulder, and anterior chest w all, and this finding
cu lar Su rgery University of Michigan, Ann Arbor, MI 48109 can aid in the diagnosis.
349
Table 3 1 .1 H yp ercoa gu la ble t est in g autoimmune d isorders is approximately 13-fold higher for
d eficiencies of inhibitors of coagulation (antithrombin, pro-
Standard coagulation tests tein C, or protein S), 6-fold higher for factor V Leid en muta-
Mixing studies (if APTT is elevated) tion, and 4-fold higher for the prothrombin gene m utation
Antithrombin antigen and activity (11). The same ind ications for hypercoagulable w ork-up in
patients w ith DVT should be applied to patients with super-
Protein C antigen and activity
ficial thrombophlebitis (8). This category includ es patients
Protein S antigen without an associated history of trauma or inactivity,
APC resistance test venipuncture, malignancy, or VVs and with severe superfi-
Factor Vgenetic analysis cial thrombophlebitis, recurrence, fam ily history, early age at
presentation, and resistance to therapy.
Prothrombin 20210A genetic analysis
Homocysteine level
Antiphospholipid/anticardiolipin antibody screen ■ VENOUS DISEASE DIAGNOSIS
Factor VIII levels ■ Deep venous thrombosis
Platelet count/platelet aggregation testing
The d iagnosis of DVT m ust be m ad e w ith confirm atory
Functional plasminogen im aging, as p atients w ill be asym p tom atic at p resentation
Heparin antibodies in u p to 50% of the cases. Patients m ay com p lain of a d u ll
ache or p ain in the calf or leg. The most comm on physical
APTT, activated partial thromboplastin time. find ing is ed em a, althou gh Wells has classified patients
into a scoring system that em p hasizes the p hysical p resen-
tation. In the Wells criteria, characteristics inclu d e the pres-
■ Superficial thrombophlebitis ence of active cancer, p aralysis or p aresis, recent plaster
Superficial thrombophlebitis occurs in more than 125,000 im m obilization of the low er extrem ity, being recently
patients per year and is associated with varicose veins (VVs), bed rid d en for 3 d ays or more, localized tend erness along
pregnancy, thromboangiitis obliterans (Behçet disease), and the d istribu tion of the d eep venou s system , the entire leg
indw elling catheters. Complications of superficial throm- being sw ollen, calf sw elling that is at least 3 cm larger on
bophlebitis have been associated w ith male gender and a the involved sid e than on the noninvolved sid e, pitting
history of VTE (8). Clinically, a painful, firm, palpable cord ed em a in the sym p tom atic leg, and a history of DVT (12).
w ith inflam mation and tend erness along the affected vein, Tests for making the d iagnosis of DVT of historical inter-
and occasionally edema, are noted. There may be a history of est includ e ind irect flow examinations. Duplex ultrasound
venous puncture or intravenous canalization, traum a, phys- imaging has replaced these tests because of its high sensitiv-
ical inactivity, oral contraceptives, malignancy, or infection. ity, specificity, and reprod ucibility. Duplex ultrasound imag-
The presence of migratory superficial thrombophlebitis sug- ing includ es a Doppler flow pattern and a B-mod e image.
gests the presence of cancer (e.g., carcinoma of the pancreas Duplex imaging carries sensitivity and specificity rates
[Trousseau sign]). The incid ence of DVT associated w ith 95% (13). Accord ing to the Grade criteria for the strength of
superficial thrombophlebitis is estimated to be betw een medical evid ence, duplex ultrasound as the test of choice for
0.75% and 40%. The association of a noncontiguous DVT the diagnosis of DVT is given a 2 C level of evidence (13–15).
w ith superficial thrombophlebitis is as high as 25% to 75% in Magnetic resonance imaging may be helpful to diagnose
patients who present with involvement of both systems (9). central pelvic vein and inferior vena cava (IVC) thrombosis,
PE, the most lethal and und errecognized complication asso- w hereas spiral computed tomography (CT) scanning is used
ciated w ith this entity, occurs from 0% to 17% (10). w hen combined w ith chest imaging d uring examination for
Su p p u rative su p erficial throm bop hlebitis is associated PE (16). Even at the calf level, d uplex imaging is an accept-
w ith intravenou s catheter u se or m u ltip le p u nctu re sites able technique in symptomatic patients. Other ad vantages
second ary to intravenous d rug abu se, m ost often in the of duplex imaging include the fact that the examination is
upper extrem ity. The clinical p resentation is sim ilar to that painless, requires no contrast, can be serially repeated , and is
of nonsu p p u rative su perficial throm bophlebitis, althou gh safe during pregnancy. The test also identifies other poten-
there is often also p yrexia, leukocytosis, and bacterem ia. tial causes of a patient’s symptoms (14).
Local intravenou s catheter site infections occu r in up to 8% A single com plete technically ad equ ate negative d u plex
of cases, and bacterem ia is d etected in ap proxim ately 1 of scan is accurate enough to w ithhold anticoagu lation w ith
every 400 intravenou s catheterizations (9). Im m unocom - m inim al long-term ad verse throm boem bolic com p lications
prom ised and bu rn patients are particu larly susceptible to (17). H ow ever, all segm ents of the leg m u st have been eval-
su p erficial throm bop hlebitis. u ated su ccessfu lly. If the d u p lex scan is ind eterm inate,
H yp ercoagu lability in the setting of su p erficial throm - treatm ent m ay be based on other factors such as biom ark-
bop hlebitis is not u ncom m on. The risk of su p erficial ers. Rep eat im aging m ay be p erform ed in 48 to 72 hou rs or
throm bop hlebitis in the absence of VVs, m alignancy, or if the p atient’s sym p tom s change or w orsen. Com bining
Chapter 31 • Complications of Venous Disease and Therapy 351
clinical characteristics w ith a D-d im er assay may d ecrease ■ Pulmonary embolism

the nu m ber of negative d uplex scans perform ed (12).
Although the u se of clinical characteristics and D-d im er Almost any pulmonary symptom can mimic a PE. Chest
levels is u sefu l to rule out throm bosis, the reverse is not rad iograp h changes are infrequ ently p resent, and hem op t-
tru e. A p ositive D-d im er associated w ith a positive risk ysis rep resents p u lm on ary infarction and su ggests a far
assessm ent is associated w ith throm bosis in approxim ately ad vanced state of abnormality. The d iagnostic mod alities for
70% of cases and is not consid ered good enough to base PE are in flux. In the most recent past, the tests used includ ed
anticoagu lant therapy on (18). Other cond itions that m ay ventilation/ perfusion scanning (V/ Q) and pulmonary arte-
be confu sed w ith DVT includ e lym phed em a, m u scle riography. Unfortunately, V/ Q scanning is diagnostic in
strain, and m u scle contusion. Iliac vein obstru ction can only approximately one-third of cases, and pulmonary arte-
lead to unilateral leg ed em a and p red ispose to DVT riography m ay cau ses m orbid ity and occasional m ortality.
(May–Thu rner synd rome), w hereas the presence of a cyst Spiral CT scanning has show n significant prom ise and in
behind the knee m ay prod uce u nilateral leg p ain and many institutions has become the test of choice. Certain bio-
ed em a. Other causes of leg sw elling (usually bilateral) markers of cardiac injury, including troponin and brain natri-
inclu d e card iac, renal, or hepatic abnorm alities. uretic peptide, have now been recognized to be useful in acute
Diagnosis of incom petent venous perforators, in p lan- PE (24). For example, if the biomarkers are found present, fur-
ning for venou s stasis u lceration treatm ent, can be accom - ther testing with echocardiography is indicated to determine
plished by d u p lex w ith a sensitivity 80% (19). Ascend ing right ventricular strain and to direct thrombolytic therapy.
venograp hy m ay also be of benefit in this regard . The
d u plex scan can also be u sed to d iagnose fem oropopliteal ■ VENOUS THROMBOEMBOLISM PROPHYLAXIS
venou s reflu x reliably, w hich contribu tes to p rim ary One of the m ost com m on yet preventable com plications of
venou s varicosities in 50% (20). Saphenopopliteal reflu x m ajor su rgery and hosp ital illness is VTE (25). Prevention
shou ld also be d ocu m ented , as this m ay contribu te to p er- of VTE has received increased scru tiny from insu rers, qu al-
sistent and recu rrent venou s varicosities. ity grou p s and the Joint Comm ission. Method s for VTE
A d efinitive d iagnosis of chronic venous insufficiency p rop hylaxis inclu d e p harm acologic, m echanical, and com -
(CVI) is essential for selecting patients w ho w ill benefit binations thereof (26). The goal is to p revent VTE, w hile
most from any given intervention. A stand ard severity clas- balancing and m inim izing bleed ing occu rrence.
sification scoring system that inclu d es a Venou s Clinical Evid ence-based pharmacologic prophylaxis includ es
Severity Score (VCSS) and the m ore trad itional CEAP low -d ose unfractionated heparin (UFH ), low -molecular-
(Clinical Etiology Anatom ic Pathophysiologic) system has w eight heparin (LMWH ), fond aparinux, and w arfarin.
been d evelop ed (21). The latter is a stand ard w ay to catego- Enoxaparin and d altep arin are the LMWH s approved by
rize venou s insu fficiency, and it includ es etiology and the U.S. Food and Drug Ad ministration (FDA). Prophylac-
anatom ical inform ation. The CEAP classification allow s tic d osages for enoxaparin are either 30 mg subcutaneously
cross-com m u nication betw een physicians, w hereas the every 12 hours or 40 mg once d aily, w hereas d alteparin
VCSS allow s for the d ocum entation of therapeutic ou tcom e d osage is either 2,500 or 5,000 anti–factor Xa u nits subcuta-
for any given p roced ure. It d ifferentiates betw een reflu x neously once d aily, and fond aparinux is 2.5 mg SQ qd .
and obstru ctive com ponents that m ay aid w ith therap y. Bleed ing com p lications associated w ith p harm acologic p ro-
If fu rther interventions are p lanned , CVI is d iagnosed p hylaxis are quite low, generally less than 3% (27). Impor-
w ith both d u p lex u ltrasou nd im aging assessing valvu lar tantly, aspirin alone is not recom m end ed for prophylaxis.
reflu x and air p lethysm ograp hy (APG). APG is a noninva- Mechanical m ethod s of p rop hylaxis inclu d e p neu m atic
sive venou s assessm ent that assesses for calf m u scle com p ression d evices (PCDs) and grad ed elastic stockings.
p u m p fu nction and reflu x and obstru ctive com p onents of Mechanical p rop hylaxis w ith PCDs red u ces the incid ence
venou s insu fficiency. A recent rep ort su ggests this is m ost of DVT (26), althou gh this has not been p roven w ith the
sensitive for reflu x assessm ent, both in the d eep and sam e rigor as w ith p harm acologic agents. The effectiveness
su p erficial system s (22). H ow ever, there is no correlation of PCDs is based on overcom ing venou s stasis and increas-
w ith the p aram eters of APG and the severity of clinical ing low er extrem ity blood flow and , p ossibly, by increasing
d isease. Sim ilarly, foot venou s p ressu res or am bu latory native fibrinolytic activators. Com p liance w ith these
venou s p ressu re m easu rem ents are invasive m ethod s to d evices is a p rim ary issu e as they need to be p hysically on
qu antify venou s hyp ertension. A need le is p laced in the the lim b to p rovid e p rotection, and som e clinical cond i-
m ed ial vein of the great toe and p ressu res are taken both tions prevent this.
at rest and after calf ejection w ith com p ression. Unlike
APG, foot venou s p ressu re d oes correlate w ith venou s
clinical severity sym p tom atology (23). This test m ay be
■ Risk stratification
u sed for p rep roced u ral and p ostp roced u ral qu antification General su rgical p atients m ay have an incid ence of VTE
of therap y, althou gh it has not gained w id esp read p op u - as high as 25% w ithou t p rop hylaxis, althou gh this is
larity becau se of its invasive natu re and p roced u ral p ain based on historical series (26). Assessm ent of risk can be
for the p atient. d one by categorizing broad grou p risk (26) (Table 31.2) or
Table 3 1 .2 Th r om boem bolism r isk a n d su rgical proced ures, ad vanced age, femoral venous lines or
r ecom m en d ed p r op hyla xis major venous repairs, prolonged immobility, and prolonged
d uration of hospital stay (35). In trauma patients at high
Approximate Prophylaxis bleeding risk not receiving pharmacologic prophylaxis,
Level of Risk Risk Option d uplex ultrasound screening is appropriate w hen dictated
Low by clinical indications.
Minor Surgery 10% Non Specific Whether p resu rgical (on call to op erating room ) versu s
Mobile inpatients Early ambulation early postsu rgical ( 6 hou rs after su rgery) p harm acologic
Moderate agent ad m inistration is best is not clear, bu t it is recom -
Most general, gynecologic, 10–40% LMWH, LD-UFH BID mend ed for gynecological su rgery bu t not for orthoped ic
urologic surgeries or TID, fonda parinux su rgery (26). N o clear consensu s exists for general su rgery
Increased age, prior VTE, and/or PCD’s p atients. The institu tion of PCDs shou ld be started before
Malignancy su rgery begins, althou gh level 1 evid ence is lacking su p-
High p orting this p ractice.
Hip and knee arthroplasty 40% LMWH, fondaparinux, Placement of a vena caval filter is often done for VTE pro-
Major trauma and PCD’s phylaxis, but there is no solid evidence for this practice (26).
Multiple VTE risk factors Appropriate indications for vena cava filters include patients
with proximal DVT w hen anticoagulation is contraindicated
Modified from Geerts, W. et al. Chest 2008.
or when a failure or complication of anticoagulation occurs
(36,37). The use of IVC filters strictly for prophylaxis in the
by a scoring system based on ind ivid u al p atient factors highest risk patients requires prospective study, as does the
(28) (Table 31.3). The best system for assessing risk is d ebat- use of retrievable versus permanent filter use.
able, bu t recent research suggests u tility of the ind ivid u al Prolonged posthospital prophylaxis m ay d ecrease over-
scoring system in su rgery patient. Regard less of the system all VTE rates, as som e stu d ies su ggest that u p to one-third
u sed , the im p ortant point is to d etermine each patient’s of ep isod es of VTE occu r after d ischarge (29). Sp ecific
risk and im p lem ent ap p rop riate p rop hylaxis. Com p u ter- p atient grou p s that benefit inclu d e hip and knee replace-
generated reminders and standardized order sets seem to ment orthoped ic patients and those w ith abd om inal or
improve compliance over time, whereas passive reminders p elvic malignancies (38). For exam p le, evid ence suggests
do not (29,30). Further, standardized history and physical that continu ation of LMWH is better than p lacebo for
examination intakes w ith “built in” VTE risk assessment may extend ed 4-w eek p rop hylaxis in p atients u nd ergoing
also increase appropriate prophylaxis. abd om inal and p elvic cancer su rgery (39).
The sp ectru m of VTE risk ranges from low risk, w here Pharm acologic prophylaxis (esp ecially LMWH ) in the
no sp ecific VTE p rop hylaxis ou tsid e of early am bu lation is p resence of sp inal and ep id u ral catheters m ay increase the
ind icated , to highest risk w here both pharm acological and p otential of hematom a form ation. Factors that m ay con-
PCDs are ind icated . Specific su rgeries have various levels tribu te to this p roblem inclu d e coagu lop athy, traum atic
of evid en ce w ith d ifferen t p harm acologic agents an d catheter or need le insertion, rep eated insertion attem pts,
clinical cond itions. To su m m arize the consensu s recom - u se of continu ou s ep id u ral catheters, anticoagu lant
m end ations in general, vascu lar, u rologic, and gynecologic d osage, concu rrent ad m inistration of m ed ications that
su rgeries, p rop hylactic LDH (5,000 U TID) is as efficacious increase bleed ing, vertebral colu m n abnorm alities, old er
as LMWH for VTE prophylaxis, although bleed ing risk and age, and fem ale gend er (27). A p ractical p roblem also arises
H IT risk may be higher (Fig. 31.1) (26). In orthop ed ic in the form of d iscontinuation of the ep id u ral catheter and
patients, fond aparinux is more effective than LDH or starting and stop p ing p harm acological p rop hylaxis. Tim -
LMWH , and is recommend ed for hip and knee replace- ing of p rop hylaxis d osing shou ld be kep t in m ind . Our ow n
ment. In a meta-analysis of more than 7,000 patients, there p ractice is to allow ap p roxim ately 2 hou rs betw een pro-
w as 50% risk red u ction comp ared w ith LMWH (begu n 12 p hylaxis agent ad m inistration and catheter rem oval. It is
to 24 hours after surgery) w ith fond aparinux (begun 6 im perative to m ake sure that the prophylactic agent is not
hours after su rgery) (31). Although major bleed ing w as fu lly d iscontinued around the tim e of catheter rem oval.
increased , critical bleed ing w as not increased . Fond a-
parinux has also been effective in prophylaxis of general
med ical patients, of abd ominal surgery patients, and for
■ STANDARD THERAPY FOR VENOUS
extend ed prophylaxis after hip fractu re (32–34).
THROMBOEMBOLISM
In trauma patients without prophylaxis, DVT may occur The p rim ary treatm ent of VTE is system ic anticoagu lation,
in up to 50% of high-risk cases, and PE is the third most com- w hich red u ces the risk of PE, extension of throm bosis, and
mon cause of d eath in those surviving beyond the first d ay. recu rrence of throm bosis. Im m ed iate system ic anticoagu la-
From several series, LMWH is m ore efficaciou s than LDH tion shou ld be achieved , as recu rrence rates for VTE are
(Fig. 31.2). Sp ecific risk factors in trau m a p atients inclu d e ap p roxim ately 4- to 6-fold higher if anticoagu lation is not
sp inal cord inju ry, low er extrem ity or p elvic fractu res, therap eu tic in the first 24 hou rs (40). This is less of an issu e
Table 3 1 . 3 Th rom bosis r isk fa ct or a ssessm en t
Patient’s Name:_________________ Age: ___ Sex: ___ Wgt:___lbs
Choose All That Apply
Each Risk Factor Represents 1 Point Each Risk Factor Represents 2 Points
• Age 41–60 years • Age 60–74 years
• Minor surgery planned • Major surgery ( 60 minutes)
• History of prior major surgery • Arthroscopic surgery ( 60 minutes)
• Varicose veins • Laparoscopic surgery ( 60 minutes)
• History of inflammatory bowel disease • Previous malignancy
• Swollen legs (current) • Central venous access
• Obesity (BMI 30) • Morbid obesity (BMI 40)
• Acute myocardial infarction ( 1 month) Each Risk Factor Represents 5 Points
• Congestive heart failure ( 1 month) • Elective major lower extremity arthroplasty
• Sepsis ( 1 month) • Hip, pelvis or leg fracture ( 1 month)
• Serious lung disease incl. pneumonia ( 1 month) • Stroke ( 1 month)
• Abnormal pulmonary function (COPD) • Multiple trauma ( 1 month)
• Medical patient currently at bed rest • Acute spinal cord injury (paralysis) ( 1 month)
• Leg plaster cast or brace • Major surgery lasting over 3 hours
• Other risk factors____________________
For Women Only (Each Represents 1 Point)
Each Risk Factor Represents 3 Points
• Oral contraceptives or hormone replacement therapy
• Age over 75 years
• Pregnancy or postpartum ( 1 month)
• Major surgery lasting 2–3 hours
• History of unexplained stillborn infant, recurrent spontaneous
• BMI 50 (venous stasis syndrome)
abortion ( 3), premature birth with toxemia or growth-restricted
• History of SVT, DVT/PE
infant
• Family history of DVT/PE
• Present cancer or chemotherapy
• Positive Factor VLeiden
• Positive Prothrombin 20210A
• Elevated serum homocysteine
• Positive Lupus anticoagulant
• Elevated anticardiolipin antibodies
• Heparin-induced thrombocytopenia (HIT)
• Other thrombophilia
Type______________________________
Total Risk Factor Score

Please see Following Page for Prophylaxis Safety Considerations
Revised May 16, 2006
Prophylaxis Regimen
Total Risk Factor Score Incidence of DVT Risk Level Prophylaxis Regimen Legend
0–1 10% Low Risk No specific measures; early ambulation ES — Elastic Stockings
2 10–20% Moderate Risk ES or IPC or LDUH, or LWMH IPC — Intermittent
Pneumatic Compression
3–4 20–40% High Risk IPC or LDUH, or LMWH alone or in LDUH — Low Dose
combination with ES or IPC Unfractionated Heparin
5 or more 40–80% Highest Risk Pharmacological: LDUH, LMWH*, Warfarin*, LMWH — Low Molecular
1–5% mortality or Fac Xa* alone or in combination with Weight Heparin
ES or IPC Fac Xa — Factor XInhibitor
Prophylaxis Safety Considerations: Check box if answer is 'YES'

Anticoagulants: Factors Associated with Increased Bleeding
n Is patient experiencing any active bleeding?
n Does patient have (or has had history of) heparin-induced thrombocytopenia?
n Is patient's platelet count 100,000/mm3?
n Is patient taking oral anticoagulants, platelet inhibitors (e.g., NSAIDS, Clopidigrel, Salicylates)?
n Is patient's creatinine clearance abnormal? If yes, please indicate value ___________
If any of the above boxes are checked, the patient may not be a candidate for anticoagulant therapy and you should consider alternative prophylactic measures.
Intermittent Pneumatic Compression (IPC)
n Does patient have severe peripheral arterial disease?
n Does patient have congestive heart failure?
n Does patient have an acute superficial/deep vein thrombosis?
If any of the above boxes are checked, then patient may not be a candidate for intermittent compression therapy and you should consider alternative
prophylactic measures.
Venous thromboembolism Venous thromboembolism

prophylaxis: General, vascular, prophylaxis:
urologic, gynecologic Trauma, spinal injury, burns
Risk Factor evaluation Contra indication to

anticoagulation?
N Y
Low Moderate High
LMWH
IPC
+/– IPC
Early LMWH, LDH TID,

LMWH, LDH TID,
Ambulation fondaparinux or
fondaparinux + PCD Adequate time
PCD for hospital
for hospital course on limbs
course
N Y
N Major pelvic/abdominal DUS _ Continue use

Stop Pharmacologic
Prophylaxis ifmobile oncologic surgery Screen until mobile; low
patient threshold for
Y + DUS
Consider extended Consider IVC

pharmacologic filter
prophylaxis for 30 d
FIGURE 31.2. Algorithm for venous thromboembolism prophylaxis for
FIGURE 31.1. Algorithm for venous thromboembolism prophylaxis for gen- trauma, spinal injury, and burn patients.
eral, vascular, urologic, and gynecologic patients.
w ith LMWH as com pared w ith intravenous UFH . In ad d i- There is also early evid ence that LMWH s m ay d ecrease the
tion, anticoagu lation has been show n to prevent the d evel- incid ence of PTS (46). Taking all of the evid ence together,
opm ent of fatal PE, both d u ring the initial treatm ent and LMWH s are p referred over stand ard UFH for the initial
after the treatm ent is com plete (41). H ow ever, recu rrent treatm ent of VTE w ith a level of evid ence 1 A based on the
DVT m ay still occu r in u p to one-third of p atients over the most current American College of Chest Physicians (ACCP)
next 8 years after ad equ ate anticoagulant therap y (42). gu id elines (47).
Trad itionally, system ic intravenou s UFH has been Fond aparinu x is also efficacious for the treatm ent of
u nd ertaken for 5 d ays d u ring w hich tim e oral anticoagu la- both DVT and PE (26,48,49). Fond ap arinu x is ad m inistered
tion w ith vitam in K antagonists (u su ally w arfarin) is insti- in a w eight-based manner—5 mg for w eight 50 kg, 7.5 mg
tu ted . Becau se the IN R is slightly p rolonged by hep arin for w eight 50 to 100 kg, and 10 m g for w eight 100 kg.
p rep arations and m ost of the liver coagu lant factors have Treatm ent at least for 5 d ays w ith concu rrent ad m inistra-
long half-lives, IN R’s therap eu tic for tw o consecu tive d ays tion of oral anticoagu lation is recomm end ed , u ntil the IN R
is u su ally recom m end ed before stop p ing hep arin (43). is therap eu tic at a level of 2 to 3.
H ow ever, becau se of the need for intravenou s ad m inistra- Warfarin shou ld be begun after hep arinization is thera-
tion, frequ ent m onitoring, and the bleed ing risks of UFH , p eu tic, to p revent w arfarin-ind u ced skin necrosis, w hich
LMWH s have been ad vanced as p rim ary therap y for VTE. occu rs d u e to transient hyp ercoagu lability that m ay
LMWH s, d erived from the low er-m olecu lar-w eight range occu r after w arfarin is begu n. Warfarin inhibits p rotein C
of stand ard hep arin, d em onstrate less d irect throm bin and p rotein S before m ost coagu lation factors are inhib-
inhibition and m ore anti–factor Xa inhibition. LMWH s are ited by w arfarin. The goal for w arfarin is an IN R betw een
at least equ ivalent to UFH , if not slightly su p erior, regard - 2.0 and 3.0. The recom m end ed d u ration of anticoagu la-
ing throm bu s recu rrence, w ith a low er risk for m ajor hem - tion after a first ep isod e of VTE w ith an id entifiable risk
orrhage (44). factor(s) is 3 to 6 m onths (50). Calf level th rom bi m ay be
LMWH s m ay be ad m inistered su bcu taneously, w eight- treated w ith w arfarin for 6 to 12 w eeks. After a second
based , and d o not require m onitoring except in certain cir- ep isod e of VTE, the u su al recom m end ation is p rolonged
cu m stances (renal failu re, m orbid obesity and d u ring w arfarin u se u nless there are other m od ifying factors.
pregnancy), and thu s they m ay be given in the outp atient The d uration of w arfarin u sage in other situ ations is con-
setting (45). The u se in the outpatient setting requ ires a troversial. VTE recu rrence is increased in the p resence of
coord inated team ap p roach of m any health care provid ers. homozygous factor V Leid en and p rothrom bin 20210 A
mu tation, p rotein C or protein S d eficiency, antithrom bin the p ast. Both bovine and p orcine UFH as w ell as LMWH
d eficiency, antip hospholipid antibod ies, and u nresolved have been associated w ith H IT, althou gh the incid ence and
cancer (3). In these cond itions, long-term w arfarin is recom- severity w ith LMWH is less. Arterial and venou s throm -
mend ed , especially w ith multiple hypercoagulable states. boses have been rep orted , and even sm all exposu res to
H ow ever, heterozygou s factor V Leid en and prothrom bin heparin (hep arin coating on ind w elling catheters) can
20210 A d o not carry the same risk as their homozygous cau se the synd rom e.
cou nterparts, and the d uration of oral anticoagulation may The d iagnosis of H IT shou ld be su sp ected w hen a
be shortened . In fact, there may be no increased risk of p atient exp eriences 50% d rop in p latelet cou nt, w hen
recurrence w ith heterozygous factor V Leid en. there is a d rop in p latelet cou nt below 100,000/ L d u ring
Recen tly, tw o ad d itional criteria have been u sed to hep arin therap y, or w hen throm bosis occu rs d u ring
d eterm ine th e d u ration of an ticoagu lation. On e in volves hep arin therap y (61). The m ost frequ ently u sed test to
the am ou nt of chronic scar tissu e in the affected vein. The m ake this d iagnosis is an enzym e—linked im m unosorbent
second and p erhap s better-valid ated criterion involves assay (ELISA) that d etects the antihep arin antibod y in the
D-d im er testing obtained 1 m onth after w arfarin ad m in- p atient’s p lasm a. This test is highly sensitive bu t p oorly
istration is stop p ed (51). If the D-d im er level is elevated sp ecific. Another test that can be u sed is the serotonin
above n orm al, evid ence su ggests that w arfarin shou ld be release assay, w hich is m ore sp ecific bu t less sensitive
continu ed , as this resu lt su ggests that the p atient is still than the ELISA test (62). Once the d iagnosis is m ad e (or
p roth rom botic (52–54). One stu d y d em onstrated a statis- even initially strongly su sp ected ), cessation of hep arin is
tically significant ad vantage to resu m ing w arfarin if the the m ost im p ortant step in treatm ent. Warfarin shou ld not
D-d im er assay is p ositive as com p ared w ith rem aining be started u ntil an ad equ ate alternative anticoagu lant has
off w arfarin over 1.4-year follow -u p (OR 4.26, p 0.02) been established , to p revent p arad oxical throm bosis.
(55). LMWH s cannot be su bstitu ted becau se of high cross–
Unprovoked VTE requ ires ad d itional consid erations. reactivity w ith stand ard hep arin antibod ies. The d irect
Most believe that true unprovoked VTE requires 6 months throm bin inhibitors hiru d in (lep iru d in/ Reflu d an) and
of w arfarin ad m inistration, bu t the actu al d u ration is not argatroban are the treatm ents now ap p roved by FDA,
know n. A m u lticenter trial su ggested that for id iop athic althou gh other agents su ch as fond ap arinu x have been
DVT, low -d ose w arfarin (IN R, 1.5 to 2.0) w as su p erior to also fou nd to treat this synd rom e (63,64). Lep iru d in is
placebo over a 4-year follow -up p eriod w ith a 64% risk excreted renally and argatroban is m etabolized by the
red u ction for recu rrent DVT (56). H ow ever, a second stu d y liver. The u se of these alternative agents is given 2 C and 1
suggested that fu ll-d ose w arfarin (IN R, 2 to 3) is su p erior to C levels of evid ence (47,61,63,64).
low -d ose w arfarin in the sam e p atient group w ithou t a d if- The safety of LMWH com p ared w ith that of w arfarin
ference in bleed ing (57). These d ata together su ggest that has led to a consid eration of the long-term u se of LMWH as
for inp rovoked throm bosis, long-term treatm ent is d esir- a rep lacem ent for oral vitam in K antagonists. Rates of vein
able at an IN R of 2 to 3. In aggregate, criteria for d iscontin- recanalization have been rep orted to be higher in certain
uation of oral anticoagu lation are given a level of evid ence venou s segm ents u sing LMWH versu s trad itional oral
of 1 A (47,52–54,56,57). agents. In ad d ition, LMWH in certain cancer patients,
The m ost com m on com p lication of anticoagu lation is w hen u sed for 6 m onths, has been associated w ith
bleed ing, and therapy d u ration m ust be balanced against d ecreased rates of VTE recu rrence and even m ortality w ith-
this risk. With UFH , bleed ing occu rs in approxim ately 10% ou t d ifferences in m ajor bleed ing (65).
of cases over the first 5 d ays; w ith w arfarin at an IN R at 2 to The u se of once-a-d ay as com p ared w ith tw ice-a-d ay
3, the incid ence of m ajor bleed ing is approxim ately 6% p er LMWH d osing has been assessed . In a m eta-analysis of
year. When u sed for p atients w ith VTE, m ajor bleed ing has m ore than 1,500 p atients w ith VTE, there w ere no signifi-
been rep orted in 0% to 7% of patients and fatal bleed ing in cant d ifferences in recu rrent throm boem bolism , throm bo-
0% to 2% of p atients (58). A m eta-analysis reported a 9.1% sis size, hem orrhagic events, and m ortality betw een
rate of hem orrhagic com p lications for anticoagu lation con- once-a-d ay and tw ice-a-d ay d osing (66). H ow ever, patients
tinu ed for m ore than 3 m onths. To d ecrease bleed ing, oral w ith m arked obesity, and those w ith cancer m ay still bene-
d ose ad ju stm ents, the u se of anticoagu lation clinics, and fit from tw ice-a-d ay d osing (67).
even hom e m onitoring have been su ggested .
Another com p lication of heparin is H IT. This cond ition
occu rs w hen a hep arin-d ep end ent antibod y im m u noglob- ■ ALTERNATIVE/FUTURE MEDICAL
ulin bind s to p latelets and activates them , lead ing to TREATMENTS FOR DEEP VENOUS
throm bocytop enia and throm bosis (59). H IT occu rs in 0.6%
to 30% of p atients in w hom heparin is ad ministered . While
THROMBOSIS/PULMONARY EMBOLISM
morbid ity and m ortality has been high, early d iagnosis and Tw o classes of agents for VTE treatm ent being d eveloped
app rop riate treatm ent have d ecreased these rates (60). H IT inclu d e d irect thrombin inhibitors and sp ecific factor Xa
usu ally begins 3 to 14 d ays after heparin is begu n bu t m ay inhibitors. Ximelagatran, a direct thrombin inhibitor, showed
occu r earlier if the p atient has been exp osed to hep arin in great prom ise a few years ago to replace w arfarin. H ow ever,
Table 3 1 . 4 Com p a r ison of p r op er t ies of r iva r oxa ba n , a p lxa ba n , a n d

d a blga t ra n et exlla t e
Property Rivaroxaban Aplxaban Dablgatran Etexllate

Target Factor Xa Factor Xa Thrombin
Route of Administration Oral Oral Oral
Prodrug No No Yes
Bioavailability, % 80 50 6
Time to peak drug level, h 3 3 2
Half-life, h 9 9–14 14–17
Frequency of administration Once-daily Twice-daily Once or twice-daily
Drug interactions Potent CYP3A4 and Potent CYP3A4 and Proton pump inhibitors
Renal excretion, % P-glycoprotein inhibitors P-glycoprotein inhibitors 80
Safe in pregnancy 66 25 No
Antidote No No No
No No
From Gross PL, Weitz JI. New anticoagulants for treatment for venous
Thromboembolism. Atheroscler Thromb Vasc Biol 2008;28:384. (Used with permission)
xim elagatran cau sed an elevation in liver fu nction tests trials of p atients w ith p roxim al DVT and p hase III trials
in u p to 6% of p atients an d w as n ot ap p roved . A relative (68,69,72,73).
of th is d ru g, d abigatran etexilate, is cu rren tly u n d ergo- Other antithrom botic agents are being evalu ated ,
in g p hase III stu d ies in th e p rop hylaxis and treatm ent inclu d ing oral heparins; other d irect throm bin inhibitors
of VTE an d h as m et a n on in flam m atory target to en oxa- su ch as bivaliru d in; d efibrinating agents su ch as ancrod ;
p arin in p rop h ylaxis for orth op ed ic p roced u res. Im p or- anti-inflam m atory agents su ch as P-selectin inhibitors; fac-
tan tly, th ere h ave n ot been elevation s in liver en zym e tor VIIa inhibitors; tissu e factor p athw ay inhibitor; and
levels or acu te coronary events so far (Table 31.4) activated p rotein C (74,75). The u se of P-selectin inhibitors
(68,69). is an area of ongoing research in ou r laboratory. An anti-
Fond ap arinu x an d its relative, id rap arinu x, are m ost inflam m atory approach u ses an antithrom botic agent that
sim ilar to LMWH , as they target factor Xa w ithou t inhibit- d oes not cau se d irect anticoagu lant activities and p resents
ing throm bin. Th ese su bcu taneou sly ad m inistered d ru gs the p ossibility of an agent that p revents throm bu s am p lifi-
d em onstrate a half-life of 17 h ou rs for fon d ap arinu x an d cation w ithou t bleed ing p otential.
80 to 130 h ou rs for id rap arinu x (com p ared w ith 4 h ou rs
for LMWH ) an d exh ibit no en d othelial or p rotein bind -
ing. N either of these d ru gs p rod u ces throm bocytop enia,
■ VENA CAVA FILTERS
an d fond ap arin u x h as been su ggested as a treatm en t for The p rim ary ind ications for IVC filters inclu d e a com p li-
H IT. cation of anticoagu lation, a contraind ication to anticoagu -
Id rap arinu x w ith the longer half-life in an op en-label, lation, and / or failu re of an ticoagu lation (Table 31.5).
noninferiority trial of 2,904 DVT p atients and 2,215 PE Protection from PE has been 95% by using cone-shaped
p atients d id not m eet the noninferiority requ irem ent for w ire-based permanent IVC filters over the past 30 years (76).
PE (70). In ad d ition, in a stu d y of long-term treatm ent in As the IVC filter has achieved success, its ind ications have
DVT/ PE p atients, m ajor bleed ing w as a significant p rob- w id ened . These ind ications inclu d e now a free-floating
lem , w ith three intracranial bleed ing ep isod es noted (70). thrombus tail longer than 5 cm, if anticoagulation risk is
Id rap arinu x d evelop m ent has been halted . H ow ever, excessive (i.e., older patient w ith DVT or follow ing major
id rap arinu x is being biotinylated (a d ru g called SSR trauma), w hen the risk of PE is very high, and to allow for
126517) so that it can be reversed w ith avid in, as there is p eriop erative ep id u ral anesthesia (77–79). Devices can be
cu rrently no antid ote for id rap arinu x. Phase III trials are either perm anent or retrievable.
u nd er w ay (71). Filters are placed in an infrarenal location in m ost cases.
N ew oral anti–factor Xa agents are being d evelop ed . H ow ever, they m ay be placed in the su prarenal or the supe-
Rivaroxaban and apixaban are the tw o agents furthest rior vena caval location in certain situations. Suprarenal
along in the d evelopm ent (Table 31.4). Rivaroxaban has placem ent ind ications inclu d e high-lying clot, p regnancy
66% renal excretion, w hereas apixaban has only 25% renal or u se in w om en of child bearing age, or p reviou s filter
excretion (68,72). Rivaroxaban is in phase II trials and filled w ith clot or that has failed . Sep sis is not a contraind i-
phase III trails show ing good resu lts in the prophylaxis and cation to the u se of w ire-based filters since the trap p ed
treatm ent of DVT, w hereas ap ixaban is in both p hase II m aterial can be sterilized by antibiotics ad m inistration.
Table 3 1 .5 Ven a cava fi lt er p la cem en t mad e on an ind ivid ual basis. N o increase in d irect throm-
in d ica t ion s a n d com p lica t ion s botic complications has been observed in patients w ith tw o
filters (86). For suprarenal filters, no greater complication
Indications Complications rate has been found than for the infrarenal location. In a
Contraindication to anticoagulation Placement series of 124 consecutive patients w ith suprarenal Greenfield
Complication of anticoagulation • Site bleed/thrombosis filters, no renal failure second ary to renal vein thrombosis
Failure of anticoagulation • Malposition w as d ocumented (87). In patients w ith malignancy, the risk
• Pulmonary embolism of thrombotic renal vein occlusion may be higher (88).
• Guidewire entrapment Long-term d evice-related com p lications, inclu d ing fil-
Device ter m igration, are less com m on than p reviou sly thou ght, as
• Migration resp iratory variation m ay accou nt for as m u ch as 20 m m of
• Occlusion
m ovem ent as d ep icted on p lain abd om inal rad iograp hs
• 1° failure
taken at d ifferent tim e p oints. Cu rrent rates of m igration of
Late
• Strut fracture
20 m m rates are 9% to 11% (82). A large IVC ( 28 m m
• Penetration d iam eter) need s to be im aged before the filter is p laced ,
• Wire ensnarement and either bilateral iliac venou s filters or a bird ’s nest IVC
(other procedure) filter shou ld be u sed . Excessive filter tilt is another p oten-
• 1° failure tial com p lication. This m ay occu r w ith stru t d eploym ent
into a vessel orifice or m isp lacem ent of the sheath d evice at
the tim e of p lacem ent. Som e rep orts have su ggested that
increased filter tilt m ay d ecrease the effectiveness of the fil-
Filters m ay be placed u nd er x-ray gu id ance or by using ter for trap p ing PE, bu t little objective d ata support this
either external u ltrasound or intravascu lar u ltrasou nd . contention u nless the tilt is 15% off the axial m id line (36).
External u ltrasou nd m ay be ineffective in the face of m or- Device failu re, d efined as recu rrent PE d esp ite a tech-
bid obesity, overlying bow el gas, or the p resence of op en nically good p lacem ent, m ay occu r in 2% to 5% of p atients
abd om inal w ou nd s (80). Other than one rand om ized (37,86,89). One w ay to d ecrease this risk is to have the
prosp ective stu d y on the u se of filters as treatm ent of DVT p atient concu rrently anticoagu lated if the p atient has a
(w hich is not how filters are trad itionally u sed ), the u se of p articu larly m alignant form of hyp ercoagu lability and if
IVC filters is given a 2 C level of evid ence based on ACCP there are no contraind ications to anticoagu lation. For
gu id elines (47,81). exam p le, if the p atient has a lim ited contraind ication to
Filter com plications are categorized as periproced u ral, anticoagu lation for w hich the filter is p laced bu t has a p er-
early d evice-related , and long-term d evice-related (Table sistent risk of VTE, anticoagu lation in the setting of a filter
31.5) (82,83). Periproced u ral com plications inclu d e bleed - is ind icated . IVC occlu sion after filter p lacem ent is a
ing, PE at the tim e of filter d eploym ent, d evice-sp ecific m is- d read ed com p lication that m ay occu r in the early or late
placement, or inability to insert the d evice (84). The m ost setting and m ay lead to p hlegm asia ceru lea d olens in u p
com m on com p lication is bleed ing, bu t cessation of hep arin to 24% of p atients w ho are u nable to be anticoagu lated
arou nd the tim e of insertion can lessen this risk. As the (90). Variou s rates of IVC occlu sion have been d ocu -
venou s system has generally low pressure, the risk of m ented w ith all filter typ es and m ay be highest w ith the
bleed ing is not high relative to arterial pu nctu re. The u se of bird ’s nest filter or the Trap Ease-typ e filter (91–93). The
gentle firm pressure w ith sheath rem oval is im portant. lack of p rosp ective rand om ized trials w ith regard to sp e-
Periproced ural PE m ay occu r if the filter is d eployed cific filter typ e, p articu larly in the long term , lim its d ata
throu gh a throm bu s (85). Du plex assessm ent of d istal iliac abou t IVC occlu sion rates. The best inform ation com es
vein throm bu s involvem ent and cavograp hy to assess iliac from the Greenfield d atabase, w ith ap p roxim ately 3,200
vein p atency can m inim ize this com plication. Conversely, p atients old er than 27 years, show ing an overall IVC
m any filters can be p laced throu gh ju gu lar or u p p er arm occlu sion rate of ap p roxim ately 2% to 4% (86,94). Filter
veins as the d elivery system s are now low er p rofile. occlu sion m ay be cau sed by the filter p erform ing its fu nc-
Early d evice-related complications usually involve filter tion by trap p ing a m assive PE or as a com p lication of the
d ep loym ent. As u ser experience has increased , failu re to filter cau sing an IVC throm bosis.
d ep loy the filter has becom e very uncom m on. Vena cava When an IVC occlu d es acu tely, the p atient m ay becom e
filters are generally placed at the level of L2–L3 for IVC hyp otensive. It is im p ortant to d ifferentiate an acu te mas-
placement and T12–L1 for suprarenal filter placement. Mis- sive PE (filter failu re) in a p atient w ith a p atent IVC from an
placement of the filter may occur if cavography or ultra- occlu d ed IVC and norm al p u lm onary artery. This d istinc-
sound imaging is not used. For example, there is a 20-fold tion can be m ad e by bed sid e d etection of jugular venous
increased risk of misplacement if only external bony land - d istention. If d istension is evid ent, it is likely that the
marks are employed (37). If misplacement is evid ent and the p atient has right heart failu re and throm bolytics and vaso-
filter ’s efficacy is thought to be compromised , the d ecision p ressor agents m ay be ap p rop riate (82). H ow ever, if the
w hether or not to place a more proximal filter need s to be p atient has intravascu lar volu m e d ep letion d u e to an
occlu d ed IVC, large volu m e resuscitation is mand atory. ■ THROMBOLYTIC AND SURGICAL PROCEDURES
Any patient w ith an IVC filter w ho d evelops su d d en low er
FOR DEEP VENOUS THROMBOSIS AND
extrem ity ed em a need s an u rgent caval d uplex exam ina-
tion, and , if technically unsatisfactory, a cavogram . PULMONARY EMBOLISM
Several strategies are available to treat IVC occlusion. For The incid ence of CVI after ap p rop riate anticoagu lant treat-
an acute thrombus, full anticoagulation w ith heparin fol- m ent for DVT has been rep orted as 23% after 2 years, 28%
lowed by catheter-directed thrombolysis may alleviate the after 5 years, and 29% after 8 years (42). Thu s, the u se of
problem. If the thrombus is older, catheter suction embolec- throm bolytic agents to rap id ly d ecrease throm bu s load
tomy and d issolution by a mechanical thrombus fragm enta- m ay d ecrease the long-term sequ elae. By d u p lex u ltra-
tion d evice may be performed (95,96). If occlusion is recent, sou nd , sp ontaneou s lysis tim e is 2.3- to 7.3-fold longer in
one may place a protective suprarenal filter and then navi- segm ents that reflu x than in segm ents w ithou t reflu x (109).
gate in the perifilter plane to recanalize the IVC, by using a System ic throm bolysis in tw o sm all series revealed a
stent to push the filter against the IVC w all (97). d ecrease in CVI w ith strep tokinase, as op p osed to sys-
Chronic occlu sions w ith minim al sym ptom s shou ld be tem ic hep arin anticoagu lation. H ow ever, resu lts d ep end
managed exp ectantly. If the filter becom es full of throm bu s, on com p lete th rom bolysis an d as the ability to p red ict
its effectiveness for trapping PE is m arked ly red uced and a com p lete lysis is p oor, com bined w ith its bleed ing p oten-
sup rarenal filter need s to be placed , as PE m ay occu r in u p tial, th rom bolysis is u sed infrequ ently. H ow ever, ad m in-
to 33% of p atients (98). istration of th rom bolytics d irectly in to ven ou s th rom bi
Prophylactic IVC filters that are p laced for patients at h as in creased in p op u larity an d h as led to the p u blication
high risk for VTE, such as those w ith m ajor traum a have of a nation al th rom bolysis registry (110,111). In 473
low to im m ed iate com plication rates, and long-term DVT p atients, 287 of w hom u nd erw ent follow -u p , 312 u roki-
has been d ocu m ented in u p to 44% (99,100). Whether this n ase in fu sions in 303 lim bs w ere rep orted . Venou s
significant DVT rate w ou ld have occu rred w ithou t filter throm bi w ere n oted in the iliofem oral segm ent in 71% of
placem ent is u nknow n. Long-term m orbid ity after p rop hy- cases alon e, w ithou t IVC involvem ent in 79%, and
lactic IVC filter placem ent is usu ally d u e to the d evelop- inclu d ing th e IVC in 21% of cases. Patien ts h ad acu te
ment of DVT and subsequ ent CVI (101). In one series of venou s throm bosis in ap p roxim ately tw o-th ird s of cases,
ped iatric p atients w ho had filters p laced for prop hylaxis 16% had chronic venou s throm bosis, and 19% had com -
from 19 m onths to 14 years, no PE, IVC throm bosis, or bined acu te and chronic ven ou s throm bosis. Ap p roxi-
migration w as d ocu m ented (102). m ately 30% had a p rior DVT. Com p lete th rom bolysis w as
Less com m on filter com p lications inclu d e ensnared achieved in 31%, w hereas p artial lysis w as achieved in
guid ew ires, either at the tim e of placem ent (m ore comm on 52% of cases. Acu te DVT and no history of DVT p red icted
w ith a ju gu lar ap p roach) or at a remote tim e, w ith a w ire su ccess, and com p lications inclu d ed m ajor bleed ing
for another p roced u re or d evice (e.g., central venou s n ecessitating blood p rod u cts in 11% and m inor bleed ing
access) (83,103). The J-w ire can becom e caught by the stru t in 16%. Intracran ial h em orrhage rate w as 0.2%, su bd u ral
apex fixation. Stand ard end ovascular techniques u sing h em orrhage rate w as 0.2%, an d m ortality w as 0.4%.
snares and catheters to straighten the J-w ire allow d isen- Patency at 12 m on th s w as 79% if lysis w as com p lete, 58%
gagem ent. If a w ire is placed for venou s access and the w ith 50% lysis, and 32% w ith 50% lysis. Absence of
operator is u naw are that a filter is present, significant p rob- valvu lar reflu x w as noted in 72% of cases if there w as
lem s m ay occu r if the w ire cannot be pulled ou t. It is com p lete lysis.
incum bent on the operator to rem ove the w ire carefu lly, Im p ortantly, aggressive therap ies have been found to
and if retrieval is not easy, flu oroscopy is u sed to id entify im p rove the qu ality of life. A sm all rand om ized stu d y
w here the w ire is ensnared . If gu id ew ires are rem oved d em onstrated that throm bolysis is su p erior to anticoagu la-
forcefu lly, the filter m ay fractu re and end up in the heart. tion in p atients w ith iliofem oral DVT (112). The use of
Filter strut fractu re m ay be d em onstrated at late follow - throm bolytic agents for DVT is now given a 2 B level of evi-
up by d u p lex u ltrasonograp hy or by a CT scan. Fractu re d ence (47).
rarely cau ses a com plication, as the struts and the d evice Su rgical ap p roaches for PE are ind icated for p atients
are w ell incorp orated via attachm ent sites. Stru t fractu re is w ith m assive PE w ith hyp otension w ho requ ire large
more com m on in the su prarenal location as greater IVC d oses of vasop ressors. These are often p atients in w hom
motion occu rs in this area. Penetration of hooks into the throm bolysis has been u nsu ccessfu l. The techniqu e of
aorta or sm all bow el has been d ocum ented but rarely has op en p u lm onary em bolectom y is associated w ith high
clinical consequ ences. Retroperitoneal hem orrhage has rates of m orbid ity and m ortality. Tod ay, op en p u lm onary
been d ocu m ented (104). Renal penetration w ith resu ltant em bolectom y is lim ited to those w ho requ ire m anu al car-
hyd ronep hrosis and sm all bow el obstru ction have been d iac m assage for hyp otension or w hen catheter p u l-
d ocum ented only by case reports (105–107). Intracard iac m onary em bolectom y fails. In the fu tu re, there m ay be a
migration of a filter is rare ( 0.1%) and usually necessitates m ore exp and ed role for p u lm onary em bolectom y (113).
either an op en surgical proced u re or a catheter-based pro- Catheter-d irected throm bolysis is w ell accep ted for
ced ure w ith a snare to rem ove the filter (108). axillary/ su bclavian venou s throm bosis, p articu larly effort
throm bosis in young p atients (114). More rapid throm boly- less than 20% have been rep orted . The incid ence of PE d ur-
sis d ecreases long-term risk of sw elling and d ep end ence of ing the first w eek after thrombectom y is equivalent to the
venou s collateralization for outflow (115). Su bclavian vein incid ence w ith only anticoagu lation. Throm bectom y has
angiop lasty and stenting for exertional axillary/ su bclavian p rim arily been u sed for lim b-threatening p hlegm asia. Clin-
venou s throm bosis have been reported (116), bu t the stents ical su ccess has been rep orted betw een 42% and 93% (125).
may crim p , m igrate, or erod e throu gh the vein, given The largest series of 77 legs w ith a follow -u p betw een 5 and
up p er shou ld er outlet m otion. A thoracic ou tlet d ecom - 13 years revealed m aintenance of p atency but a stead y
pression p roced u re is efficaciou s, as thoracic ou tlet com - d ecline in valvu lar com p etence (126).
pression m ost often causes the u nd erlying venou s stenosis. Venous thrombectomy may also be u sed in situations of
It is im p ortant that the p atient u nd ergo p ositional p hlebog- significant iliofemoral thrombosis to d ecrease postthrom-
rap hy if the axillary/ su bclavian axis is p atent to confirm botic sequ elae w hen thrombolysis fails or is contraind i-
extrinsic com pression of the axillary and subclavian veins cated . In the only stud y comparing iliofemoral venous
at the thoracic ou tlet. Generally, thoracic outlet d ecom p res- thrombectomy w ith anticoagulation (31 p atients) w ith anti-
sion follow s throm bolysis. Op erative tim ing, w hether coagulation alone (32 patients), iliofemoral vein patency
im m ed iate or after a d elay to allow for the vein w all inflam - w as better (76% vs. 35%), femorop opliteal p atency w as bet-
matory resp onse to su bsid e, is controversial. In cases of ter (52% vs. 26%), and the clinical outcome w as improved at
second ary axillary/ su bclavian DVT d u e to ind w elling 6 months (40% asymptomatic vs. 7%) (126). At 10 years, the
catheters, anticoagulation along w ith the rem oval of the nu m ber of p atients available for follow -u p had d ecreased to
catheter is ind icated . The d uration of anticoagu lation 13 (thrombectomy) and 17 (anticoagu lation-alone). Patency
shou ld be ind ivid ualized , reflecting the p atient’s throm - rem ained better in the throm bectom y group (83% vs. 41%),
botic risk—u su ally 3 m onths. Patch venoplasty is also as d id the absence of pop liteal reflux (78% vs. 43%).
recom m end ed if p ersistent venou s narrow ing is p resent
after thoracic ou tlet d ecom pression. The m ain com p lica-
tions of thoracic outlet d ecom pression are bleed ing, lym -
■ VENOUS VARICOSITIES
phatic leak, infection, recu rrent throm bosis, and brachial VV disease is a common problem. By some estimates, it may
plexu s nerve inju ry (117). account for up to 2% of all health care costs w ithin the
Throm bolytic therap y for PE rem ains controversial. United States, a figure that approaches approximately $1 bil-
Althou gh agents lyse throm bu s effectively, recurrence rates lion annually (127). It is estimated that VVs of the low er
and p atient m ortality have not been im proved . H ow ever, extremities are present in 15% to 20% of the population (128).
the original stu d ies w ere not p ow ered to ad d ress this ou t- The exact cau se of VVs is not know n, although several
com e. Resu lts have been optim ized w hen p atients are factors p lay a role in the etiology. Venou s hypertension,
you ng, the em bolu s is fresh ( 48 hou rs old ), and the em bo- valvu lar incom p etence, and reflu x from the d eep to the
lus is large. Strep tokinase, u rokinase, and tissu e p lasm ino- superficial system are involved in VV d evelopm ent and
gen activator have all been u sed (118). These agents rap id ly p rop agation. Other factors inclu d e genetic and fam ilial
d issolve clot, bu t by 7 d ays, the ad vantages for all three p red isp osition, local hem od ynam ic forces su ch as pro-
agents d ecrease. Thu s, the benefit of throm bolytic agents longed p eriod s of stand ing, and circu lating levels of estro-
for PE ap p ears to be greatest in those 10% of patients w ho gen horm ones (128). Previou s DVT m ay also p red isp ose to
w ou ld d ie as a resu lt of m assive PE in the first hou r after later d evelop m ent of VVs (42).
the PE occu rs. H ow ever, recent d ata suggest that throm bol- All p atients should receive conservative treatm ent,
ysis m ay be useful in patients w ith right ventricu lar d ys- inclu d ing good com p ression, w eight loss, exercise to
fu nction w ithou t hem od ynam ic instability and p atients im p rove calf m u scle p u m p fu nction, and interm ittent leg
w ith evid ence of right heart changes (119–124). elevation. Com p ression inclu d es grad ed com p ression
stockings, 20 to 30 m m H g for m od erate d isease and 30 to
40 m m H g for m ore severe d isease (129). Rand om ized con-
■ Venous and pulmonary thrombectomy trolled trials have d emonstrated a 50% red u ction in the
Iliofem oral venou s throm bectom y resu lts in m echanical d evelop m ent of the PTS in p atients treated w ith com p res-
clearing of the venou s circulation and m ay be com bined sion stockings after DVT, and other trials have d em on-
w ith the creation of a tem p orary arteriovenou s fistu la. strated at least sym p tom atic imp rovem ent (130,131).
Throm bectom y u ses a Fogarty balloon catheter p assed Although it m ay seem that a com pression regim en is d iffi-
from the fem oral vein d uring Valsalva m aneu vers. The cu lt to com p ly w ith and u ncom fortable, stu d ies aim ed at
arteriovenou s fistu la is fashioned su ch that it can be taken evalu ating com p liance w ith com p ression therap y have
d ow n by nonsu rgical end ovascu lar techniques and pro- d em onstrated com p liance rates of 5 hou rs a d ay w earing
vid es rap id blood flow throu gh the iliac venou s system . com p ression stockings ap p roaching 75%.
Com p lete venography in the operating room is recom - When consid ering op eration for venou s d isease, con-
mend ed , as back-bleed ing is u nreliable for the assessm ent sid eration m ust be given to both the sup erficial varicosities
of com p lete throm bus clearance. Back-bleed ing can occu r and accom p anying d eep venou s reflu x. Op eration is ind i-
from a d isobliterated sid e-branch only. Recurrence rates cated for su p erficial venou s insu fficiency w ith sym p tom s
of leg heaviness, soreness, sw elling, or fatigue. Ind ications extension, 11 limbs (2.5%) w ith superficial thrombophlebitis,
for rem oval of varicosities inclu d e pain over the varicosi- and one 1 PE. Bruising was assessed at the first postopera-
ties, p reviou s throm bophlebitis, and bleed ing. Operative tive visit, and data w ere available for 303 limbs (67.5%).
management may be u sefu l in the treatm ent of associated Bruising w as minimal in 48 limbs (15.9%), mod erate in 77
skin changes, inclu d ing hyp erpigm entation and severe (25.4%), and no bruising w as apparent in 178 (58.7%). There
venou s u lcers, althou gh m any ulcers w ill heal w ith com - w ere 9 cases (2.0%) of cellulitis in patients’ limbs, 4 (0.9%) of
pression alone. Although the ESCH AR trial d em onstrated postoperative fluid collections requiring further interven-
sim ilar rates of venou s u lcer healing in grou p s treated w ith tion, 4 (0.9%) of neovascularization and perivenous inflam-
conservative m anagem ent and VV su rgery, the grou p mation, and 2 (0.5%) of paresthesias (135).
receiving su rgical treatm ent had a significantly red u ced In p rincip le, rad iofrequ ency ablation (RFA) is qu ite sim -
rate of recu rrence—12% versus 28% (129). ilar to laser ablation in that it u ses a heat sou rce placed
Contraind ications to operative treatm ent for VV d isease insid e the greater saphenou s vein to prod uce vascular and
includ e the presence of arterial insufficiency as a cause for end othelial d am age and occlu sion of the treated vein. In
leg d iscom fort or prim ary lym phed em a as a sou rce of RFA, d irect heating cau ses contraction of the collagen in the
sym ptom s. Deep venous obstru ction, inclu d ing active vessel w all and loss of the end othelial lining, to occlu d e the
DVT, shou ld p rom p t postponem ent of treatm ent. In ad d i- vein. For both techniqu es, p ostop erative ap p lication of a
tion, active skin infection or p regnancy shou ld d elay op er- com p ressive d ressing is recom m end ed . RFA tend s to cause
ative treatm ent. less bruising and p ain p ostproced u re than laser ablation.
Ligation, d ivision, and stripping of the great sap henou s As p ersistence of VVs m ay be related to the continued
vein constitu tes the stand ard , tim e-tested , tried , and tru e p resence of incom p etent p erforating veins, m ultiple
treatm ent for VVs. The rationale behind this proced u re is ap p roaches for the correction of incom p etent p erforating
that it allow s the correction of the reflu x p resent in the veins have been ad vocated . One ap p roach that has been
lim bs of patients suffering from VV d isease and d ecreases u sed w ith som e su ccess bu t less com m only u sed now is
recurrence. Form al stripp ing has a low rate of recu rrence su bfascial end oscop ic p erforator ablation. Minim ally inva-
and is the m ost d efinitive option for correction of sap hesive ap p roaches have gained enthu siasm for the low er leg
nous reflu x contribu ting to VV d isease. Perhaps the longest and calf, as this is a site m ore p rone to the m ost severe
follow -u p is a series pu blished in 2001, based on clinical sequ elae of venou s insu fficiency inclu d ing stasis p igm enta-
assessm ent and d u p lex scan of p atients w ho had u nd er- tion and stasis d erm atitis (136). Fu rther op erative treat-
gone VV excision 31 to 39 years previou sly. In this long- m ent of p erforating veins in the thigh and u p p er leg is
term follow -u p , the rate of recu rrence w as 47%. In the technically sim p ler and associated w ith a low er com p lica-
Gloucester stu d y, how ever, the risk of recu rrence at u p to tion rate than sim ilar treatm ent in the calf. Interruption of
12 years w as ap p roxim ately 10% w ith ligation and strip - p erforating veins has been su ggested to d ecrease venous
ping com p ared w ith nearly 30% for those und ergoing liga- u lcer healing time and increase tim e to recu rrence in legs
tion only (reactive risk (RR) 2.65, 95% confid ence interval w ith severe venou s u lceration (136–138).
[CI] 1.20 to 5.84, p 0.012). Less d rastic than total ligation For the treatm ent of sm all ( 4 mm ) VVs that pose pri-
and strip p ing is ligation and d ivision of the sap henous vein m arily a cosm etic p roblem , the u se of sclerosing agents has
w ith interru p tion of specific perforating veins. This p roce- been highly effective. This typ e of treatm ent, how ever, is
d u re allow s the preservation of the saphenou s vein. less su ccessfu l in treating larger varicosities. The u nd erly-
The p ractice of p hysically rem oving the sap henou s vein ing concep t is that the injected agent d am ages the vascu lar
has been alm ost com pletely replaced by saphenou s vein end otheliu m , lead ing to obliteration of the vein lu m en.
ablation. Endoluminal ablation of the great saphenous vein, Many sclerosants have been tried , inclu d ing sod iu m m or-
provid ing functional ablation w ithout requiring formal strip- rhu ate, sod iu m tetrad ecyl su lfate, ethanolam ine oleate, and
ping, was first reported by Boné in 1999, and the first English p olid ocanol. The only sclerosant ap p roved in the United
language report followed, by Navarro, in 2001 (132,133). States is sod iu m tetrad ecyl su lfate.
Endovenous ablation uses a heat source (either a laser emit- In part becau se trad itional sclerotherap y has been
ting diode or a radiofrequency probe) to induce occlusion of u nsu ccessfu l in p rovid ing ad equ ate closu re of larger VVs,
the great saphenous vein. In laser ablation, hemoglobin in cir- the techniqu e of creating a foam for injection has been
culating red blood cells acts as a chromophore. Although ad vocated by som e. Cu rrently, there are no foam scle-
some damage is caused to the vein wall directly in the path of rosants com m ercially available in the United States; how -
the laser, the heat produced by the interaction of the laser ever, a foam may be created by m ixing available sclerosants
with the red blood cells causes the formation of steam bub- w ith air. In general, this has been regard ed as a relatively
bles, which lead to thermal injury to the interior of the vein. safe and effective p roced u re, and a recent system atic
Endothelium is d amaged and denuded, and occlusion of the review fou nd a rate of occlu sion of 87%, less than that asso-
treated segment ensu es (134). In our series of 460 limbs in ciated w ith su rgery bu t greater than that typ ically seen
364 patients with 443 successful endovenous laser therapy w ith liqu id sclerotherap y. In this analysis, the rate of
and 135 concomitant procedures we noted 3 limbs (0.7%) ad verse events w as rare, w ith PE and DVT each occu rring
with DVT, 32 lim bs (7.2%) w ith saphenofem oral throm bu s in 1% of p atients, visu al d istu rbance in 1%, and head ache
in 4% (139). H ow ever, althou gh there have been rep orts of of the time. With calf vein excision in the lesser saphenous
d em onstrated m icroembolic phenom ena d uring this proce- d istribution, the sural nerve is at the greatest risk.
d u re, seriou s ad verse consequ ences have been rare (140). Recurrence of VVs is also a know n complication, and
Stab avu lsion of sup erficial varicosities, also referred to some surgeons consid er this part of the natural history.
as ambulatory phlebectomy, remains a staple of treatment for Recurrence of VV is thought to occur by recruitment of col-
VVs although it is being su pplanted in som e centers by laterals or recanalization of the obliterated vein. To avoid
transillu m inated pow ered phlebectom y. The goal of stab this complication, it is important preoperatively to have the
avu lsion is the rem oval of sup erficial varicosities from the patient stand and to mark all the veins to avoid missing any
low er extrem ities. This techniqu e w as first d escribed in varicosities that d isappear once the patient is recumbent.
1966 and involves m aking m any sm all incisions over the Duplex-d irected varicose excision may also d ecrease inci-
varicosities and excising them w ith sp ecial hooks. sion number and d ecrease varicosity recurrence by d irecting
The complications of open phlebectomy are mostly excision and ligation of incompetent perforators (146).
minor and non–life-threatening. Infection is very rare. An Transilluminated powered phlebectomy (TriVex, InaVein,
antiseptic leg and groin wash twice the night before surgery Inc.) is d esigned as an alternative to stab phlebectomy, w ith
is recommended. There is no need for systemic antibiotic several postulated ad vantages. This technique involves the
prophylaxis. Hematoma and lymphocele occur in 0.5% of use of a handpiece transilluminator and a resector with
cases. Avoid ing d issection of the anterior tibial dorsal veins strong suction (147,148). Tumescent anesthesia is used liber-
decreases lym phocele formation (141). To decrease the risk ally during this technique, with d ermal punches to clear
of perioperative hematoma, it is important to obtain a care- blood and tumescence out of the leg. As this technique
ful history of the patient’s med ications, includ ing herbal occurs und er d irect vision, more complete excision of the VV
supplements, high-d ose vitamin E, aspirin, or other antico- clusters w ill be possible. Second , by using the instruments,
agulants, as these may potentiate a hematoma due to venous w hich require only the use of few er incisions, the more m in-
oozing. Generally, venous hematomas resolve sponta- imally invasive procedures w ill offer a more comfortable
neously and do not require additional surgical therapy or and cosmetically pleasing result than the traditional stab
transfusion. Use of a tourniquet may d ecrease bleed ing asso- phlebectomy. Comparisons of powered phlebectomy and
ciated w ith varicosity excision (142). trad itional stab avulsion have generally show ed similar out-
As an office p roced u re, venou s varicosity excision has comes, w ith trend s tow ard more postoperative hematoma
been p erform ed by using tu m escent anesthesia w here a formation and d iscomfort in the imm ed iate postoperative
d ilu te am ou nt of low -concentration lid ocaine (0.5%) w ith period, but fewer incisions (149,150).
very d ilu te ep inephrine (1:1,000,000) allow s for a large area
to be anesthetized . Earlier return to usual activities m ay be
an ad d itional benefit (143).
■ CHRONIC VENOUS INSUFFICIENCY
Peripheral nerve injury is the most common complica- Preventing complications of CVI is best achieved by appro-
tion of open phlebectom y, w ith approximately 40% to 50% of p riate u se of comp ression garments, prevention of recurrent
patients having some hypesthesia in the area of the incisions, DVT in patients w ith PTS, and w ith selective end olum inal
usually within the greater saphenous nerve distribution or op en intervention (Table 31.6) (151). The p rogression of
(144,145). Perm anent nerve injury occurs approximately 1% CVI is slow and progressive. Leg varicosities are the most
Table 3 1 .6 Ch ron ic ven ou s in su ffi cien cy p r even t a t ive m ea su r es t o r ed u ce

com p lica t ion s
Action Rx Complications Level of Evidence
Compression 20–30 mmHg None major Ia
30–40 mmHg
Address Superficial venous Saphenous and/or Local skin bruise Ib
Incompetence Perforator Ablation incisional problems
Address Venous Iliac Diagnose with MRV/ Stent Thrombosis IIb
Obstruction Venogram Stent malposition
Endolumal PTA/stent
Prevent Recurrence of DVT • Adequate duration of Bleeding; VTE recurrence Ib
anticoagulation
• Biomarker evaluation
with d-dimer
measurement
MRV magnetic resonance venography; PTA percutaneous transluminal Angioplasty.

common presentation, follow ed by ed ema and leg heavi- The primary therapy for proximal deep vein stenosis or
ness, w ith severe CVI affecting u p to 30% of patients and occlusion is end ovascular, particularly for obstructive
causing most of the associated morbid ity (42,152). The venous pathology. Endovenous angioplasty and stenting is
pathophysiology of venou s u lceration is often related to the very effective to reduce venous claudication (161), little in
failure of DVT resolution and obstruction and less com- stent restenosis or occlusion d oes occur (162), and this inter-
monly associated w ith valvular d ysfunction w ithout proxi- vention provides excellent durability (163). Endovascular
mal obstruction or incompetent perforators. Risk for PTS is venoplasty and stenting appears to w ork much better in the
associated w ith greater initial thrombus burd en, the sites of iliac vein than in other locations, and it is currently the defin-
throm bosis (proximal d istal), and inad equate anticoagu- itive approach for the patient with iliac vein compression
lation (153). synd rome (May–Thurner synd rome) (164). Major complica-
Stand ard therap y for venou s stasis u lceration inclu d es tions include bleeding, w ound infection of the incision, and
lim b elevation, grad ed com pression, and local w ou nd care. stent thrombosis. The main pred ictive factors for stent
Patient com p liance w ith grad ed com pression is critical for thrombosis include: Male gender (odds ratio [OR] 6.5),
good ou tcom es (154). The m ain com plications w ith local recent trauma (OR 5.3), and age 40 years (OR 3.8) (163).
venou s u lcer therap y are allergic reaction to the agent u sed Overall, end oluminal therapies can red uce major w ound -
and failu re of therap y d ue to intractable venous stasis related morbidity and likely decrease PTS severity by
ulceration. returning prograde venous flow in symptomatic patients.
Compression stockings are cost-effective and are better Results w ith venou s reconstructive surgery for severe
than routine care for ulcer healing (155), and nonelastic gar- m anifestations su ch as p ain or p ersistent u lceration, or
ments may be better than elastic types (156). It is important both, are better if the etiology is p rim ary valvu lar d ysfunc-
to d ecrease local bacterial colonization, promote a granulat- tion rather than p ostp hlebitic d isease (159,165). Prim ary
ing w ound bed, and provide an environment that allows valvu lop lasty and axillary vein to p op liteal vein valve
healing. It is the authors’ opinion that the Unna boot is most transp lants are selectively p erform ed . The efficacy of these
effective in this regard for a noninfected venous stasis ulcer. techniqu es is less clear, as evid ence ou tsid e of case series is
The wound is protected, and the constant compression of the u navailable and long-term p atient follow -u p is scant. Pri-
dressing d ecreases venous hypertension that impairs heal- m ary com p lications inclu d e bleed ing and throm bosis.
ing. Care must be taken to place compression dressings so Ad juncts to d ecrease these problem s includ e m eticulou s
that the Unna boot is firmly applied but is not so tight as to hem ostasis and p erip roced u ral u se of PCDs, as w ell as
create skin breakd ow n. If the patient has evid ence of celluli- ju d iciou s p eriop erative anticoagu lation. Som e investiga-
tis, systemic antibiotics are recommended . H ow ever, no evi- tors ad vocate the u se of intravenou s d extran follow ed by
dence supports routine antibiotic use for prolonged period s, cou mad inization (166). N erve inju ry and other injuries are
as this may increase bacterial resistance. Occasionally, ulcers qu ite rare. Long-term arm sw elling related to segm ental
that are long standing ( 12 months) should be evaluated for axillary vein rem oval for p op liteal vein valve transplant is
premalignant changes by local punch biopsy. m inim al as long as the p atient has a com p etent cep halic
Mu ltim od ality su rgical and end olu m inal therap y for vein that enters d istal to the area w here the vein segm ent
venou s stasis u lceration first need s to ad d ress the contribu - w ith valve is rem oved . Preop erative arm ascend ing venog-
tion of the p erforating and su p erficial venou s system to rap hy is essential in selecting the axillary venou s segm ent
this problem (157,158). Evid ence suggests su rgical treat- to u se and in confirm ing that a u sable valve is p resent.
m ent of su p erficial incom p etence su ch as sap henou s vein Reconstru ction of the IVC and iliofem oral veins for
ablation is effective for red ucing u lcer recu rrence and m ay venoocclu sive d isease m ay also be d one in lim ited settings.
be associated w ith faster healing (129) even if d eep insu ffi- By far, the m ost com m on p roced u re is a sap henous vein
ciency also exists (135). H ow ever, the strongest d ata are in fem orofem oral crossover byp ass for chronic iliac venou s
the prevention of venou s ulcer recu rrence. Comp lications obstru ction. The exp ectation for venou s reconstru ction su r-
related to sup erficial venou s ablation are listed u nd er VV gery need s to be realistic, as venou s p hysiology m akes
therap y in this chap ter. these rep airs m u ch less d u rable than arterial reconstru c-
Subfascial p erforator su rgery has been ad vanced to tions. For nonm alignant IVC occlu sion, both venou s recon-
ad d ress p erforator incom p etence (159). This techniqu e stru ctive su rgery and IVC recanalization by end ovascu lar
involves rem ote end oscopic access to visu alize and ligate techniqu es have been ad vanced . In one su rgical series, 42
the su bfascial p erforators. While occasionally used , a ran- p atients u nd erw ent 44 venou s reconstru ctions (165).
d om ized p rosp ective controlled trial su ggested little bene- Thirty-six p atients had lim b sw elling or venou s clau d ica-
fit of this techniqu e over stand ard com pression w ound care, tion, 38 had p ain, and 14 had venou s u lceration. Obstruc-
except in p atients w ith very large ulcers (160). Thu s, this tion w as acqu ired in 40 cases. For therap y, 18 p atients had
su rgical p roced u re is uncom m only p erform ed . N ew er sap henou s vein crossover grafts, 17 had ePTFE grafts
techniqu es w ith p ercu taneou s end olu m inal p erforator im p lanted (8 fem orocaval, 5 iliocaval, 3 cross-fem oral, and
ablation m ay rep resent a m ore efficacious approach, bu t 1 cavoatrial), 6 p atients had sp iral vein grafts, and 1 patient
large series are lacking. had a vein p atch angiop lasty. At 3.5-year m ean follow -up,
the second ary 3-year patency w as 62% (83% Palma and 54% 5. And reotti F, Becker RC. Atherothrom botic d isord ers: new insights
from hem atology. Circulation 2005;111(14):1855–1863.
iliocaval and femorocaval grafts). At 2 years, all ePTFE grafts 6. Perkins JM, Magee TR, Galland RB. Phlegm asia caeru lea d olens and
had a 45% patency rate (165). Thrombectomy w as required venou s gangrene. Br J Surg 1996;83(1):19–23.
in approximately 7% of patients. Thus, the procedure can be 7. Prand oni P, Bernard i E. Up p er extrem ity d eep vein throm bosis. Curr
Opin Pulm Med 1999;5(4):222–226.
recommended only in properly selected patients (167). 8. Qu enet S, Lap orte S, Decou su s H , et al. Factors p red ictive of venou s
Regard ing end ovascular interventions, a series of 120 throm botic com plications in patients w ith isolated superficial vein
patients over a 10-year p eriod has been reported . In these throm bosis. J Vasc Surg 2003;38(5):944–949.
9. Su llivan V, Wakefield TW. Su p erficial Venou s Throm bosis. In: Pearce
patients, stenotic segm ents of the IVC w ere balloon d ilated , WH , Yao JST, ed itors. Trends in vascular surgery. Chicago: Precep t
and occlu d ed segm ents w ere recanalized w hen feasible Press. 2002:463–472.
and stents p laced und er intravascu lar u ltrasou nd (168). 10. H eit JA, Silverstein MD, Mohr DN , et al. The ep id em iology of venou s
throm boem bolism in the com m u nity. Thromb Haemost 2001;86(1):
Pathology w as total occlu sion in 14% and stenoses in 86%. 452–463.
Com m on iliac vein obstruction w as concurrent in 93%. Dis- 11. Martinelli I, Cattaneo M, Taioli E, et al. Genetic risk factors for su p er-
tal reflu x w as p resent in 66%. Mod ifications of the basic ficial vein throm bosis. Thromb Haemost 1999;82(4):1215–1217.
12. Wells PS, And erson DR, Rod ger M, et al. Evalu ation of D-d im er in the
stent techniqu e w ere requ ired in recanalization of total d iagnosis of su spected d eep -vein throm bosis. N Engl J Med 2003;
occlu sions (fou r extend ing u p to the atrium ), tw o bilateral 349(13):1227–1235.
stent d ep loym ents, and nine IVC filter cases. Stent d ep loy- 13. Fow l RJ, Strothm an GB, Blebea J, et al. Inap p rop riate u se of venou s
d up lex scans: an analysis of ind ications and resu lts. J Vasc Surg 1996;
ment across the renal and hepatic veins or the contralateral 23(5):881–885, d iscu ssion 885–886.
iliac vein had no ad verse sequelae. Cu m ulative stent 14. Dou glas MG, Su m ner DS. Du p lex scanning for d eep vein throm bosis:
patency at 2 years w as 82%. Com p lete relief of p ain and has it replaced both p hlebography and noninvasive testing? Semin
Vasc Surg 1996;9(1):3–12.
sw elling at 3.5 years w as 74% and 51%, respectively. The 15. Gu yatt G, Schü nem ann H J, Cook D, et al. Ap p lying the grad es of rec-
cu m u lative rate of com plete u lcer healing at 2 years w as om m end ation for antithrom botic and throm bolytic therapy: the
63%. Overall clinical outcom e w as rated as good or excel- Seventh ACCP Conference on Antithrom botic and Throm bolytic
Therapy. Chest 2004;126(Su p p l):179S–187S.
lent in 70% (168). 16. Stein PD, Fow ler SE, Good m an LR, et al. Mu ltid etector com p u ted
Su rgical reconstru ction of the iliofem oral veins and IVC tom ograp hy for acu te p u lm onary em bolism . N Engl J Med 2006;354
in the setting of malignancy is accepted therapy, althou gh (22):2317–2327.
17. Schellong SM, Schw arz T, H albritter K, et al. Com p lete com p ression
not com mon. The risks are bleed ing and throm bosis. Anti- ultrasonography of the leg veins as a single test for the d iagnosis of
coagu lants, p erioperative PCDs to m aintain brisk venou s d eep vein throm bosis. Thromb Haemost 2003;89(2):228–234.
flow, and arteriovenou s fistulae are ad juncts that can be 18. Cornuz J, Ghali WA, H ayoz D, et al. Clinical pred iction of d eep venou s
throm bosis u sing tw o risk assessm ent m ethod s in com bination w ith
used to im p rove patency rates althou gh large com p arative rapid qu antitative D-d im er testing. Am J Med 2002;112(3):198–203.
series are lacking. Referral to a center that has exp ertise and 19. Pierik EG, Toond er IM, van Urk H , et al. Valid ation of d u p lex u ltra-
experience w ith these cases is probably the m ost practical sonograp hy in d etecting com p etent and incom p etent p erforating
veins in p atients w ith venou s u lceration of the low er leg. J Vasc Surg
measu re to ensu re few er com plications. In a series of 18 1997;26(1):49–52.
patients, no m ajor m orbid ity and no m ortality occu rred , no 20. Saku rai T, Matsu shita M, N ishikim i N , et al. H em od ynam ic assess-
anticoagu lation w as u sed , and overall clinical patency w as m ent of fem oropopliteal venou s reflux in patients w ith p rim ary vari-
cose veins. J Vasc Surg 1997;26(2):260–264.
app roxim ately 80% (169). In another series of 29 p roce- 21. Ru therford RB, Pad berg FT Jr, Com erota AJ, et al. Venou s severity
d u res for p rim ary (n2) and second ary (n27) IVC tu m ors in scoring: an ad ju nct to venou s ou tcom e assessm ent. J Vasc Surg 2000;
w hich the IVC w as rep laced w ith a large d iam eter exter- 31(6):1307–1312.
22. Criad o E, Farber MA, Marston WA, et al. The role of air p lethysm og-
nally sup ported ePTFE graft in m ost cases and three rap hy in the d iagnosis of chronic venou s insu fficiency. J Vasc Surg
patients had arteriovenous fistulae created , only tw o late 1998;27(4):660–670.
graft occlu sions occu rred at a m ean follow -up of 2.8 years. 23. Fu ku oka M, Okad a M, Su gim oto T. Foot venou s p ressu re m easu re-
m ent for evaluation of low er lim b venou s insu fficiency. J Vasc Surg
There w ere 11 late d eaths from m alignancy. In this series, 1998;27(4):671–676.
IVC rep lacem ent w as at the level of the su p rarenal segm ent 24. Ku cher N , Gold haber SZ. Card iac biom arkers for risk stratification of
of the IVC in 15 p atients, at the infrarenal segm ent of the patients w ith acu te pu lm onary em bolism . Circulation 2003;108(18):
2191–2194.
IVC in 10 p atients, at both segm ents of the IVC in 3 25. Cohen AT, Agnelli G, And erson FA, et al. Venou s throm boem bolism
patients, and at the renal vein conflu ence in 1 patient (170). (VTE) in Europ e: the num ber of VTE events and associated m orbid ity
and m ortality. Thromb Haemost 2007;98(4):756–764.
26. Geerts W. Antithrom botic and throm bolytic therap y (8th ed : ACCP
Gu id elines). Chest. 2008;133:381s–451s.
■ REFERENCES 27. Schulm an S, Beyth RJ, Kearon C, et al. H em orrhagic com p lications of
anticoagu lant and throm bolytic treatm ent: Am erican College of Chest
1. H eit JA, Cohen AT, And erson FJ. Estim ated annu al nu m ber of inci- Physicians Evid ence-Based Clinical Practice Gu id elines (8th ed ition).
d ent and recu rrent, non-fatal venou s throm boem bolism (VTE) events Chest. 2008;133(6, Su pp l):257S–298S.
in the US. Blood 2005;106(11):267a. 28. Cap rini JA. Throm bosis risk assessm ent as a gu id e to qu ality p atient
2. Prand oni P, Lensing AW, Prins MR. Long-term ou tcom es after d eep care. Dis Mon 2005;51(2–3):70–78.
venou s throm bosis of the low er extrem ities. Vasc Med 1998;3(1):57–60. 29. Ku cher N , Koo S, Quiroz R, et al. Electronic alerts to p revent venou s
3. Bau er KA, Rosend aal FR, H eit JA. H yp ercoagu lability: too m any tests, throm boem bolism am ong hosp italized p atients. N Engl J Med 2005;
too m u ch conflicting d ata. Hematology Am Soc Hematol Educ Program 352(10):969–977.
2002:353–368. 30. Tooher R, Mid d leton P, Pham C, et al. A system atic review of strate-
4. H enke P. Throm bosis d u e to hyp ercoagu lable states. Rutherford’s text- gies to im p rove p rop hylaxis for venou s throm boem bolism in hosp i-
book of vascular surgery, 6th ed . Philad elp hia, PA: Elsevier 2004;568–78. tals. Ann Surg 2005;241(3):397–415.
31. Turpie AG, Bauer KA, Eriksson BI, et al. Fond ap arinu x vs enoxap arin 56. Rid ker PM, Gold haber SZ, Danielson E, et al. Long-term , low -inten-
for the p revention of venou s throm boem bolism in m ajor orthoped ic sity w arfarin therap y for the p revention of recu rrent venou s throm -
su rgery: a m eta-analysis of 4 rand om ized d ou ble-blind stu d ies. Arch boem bolism . N Engl J Med 2003;348(15):1425–1434.
Intern Med 2002;162(16):1833–1840. 57. Kearon C, Ginsberg JS, Kovacs MJ, et al. Com p arison of low -intensity
32. Wolozinsky M, Yavin YY, Cohen AT. Pharm acological p revention of w arfarin therapy w ith conventional-intensity w arfarin therap y for
venou s throm boem bolism in m ed ical p atients at risk. Am J Cardiovasc long-term p revention of recu rrent venou s throm boem bolism . N Engl J
Drugs 2005;5(6):409–415. Med 2003;349(7):631–639.
33. Agnelli G, Bergqvist D, Cohen AT, et al. Rand om ized clinical trial of 58. Linkins LA, Choi PT, Dou ketis JD. Clinical im p act of bleed ing in
postop erative fond ap arinu x versu s p eriop erative d altep arin for p re- patients taking oral anticoagu lant therapy for venous throm boem -
vention of venou s throm boem bolism in high-risk abd om inal su rgery. bolism : a m eta-analysis. Ann Intern Med 2003;139(11):893–900.
Br J Surg 2005;92(10):1212–1220. 59. Greinacher A, Michels I, Mu eller-Eckhard t C. H ep arin-associated
34. Eriksson BI, Lassen MR. Du ration of p rop hylaxis against venou s throm bocytopenia: the antibod y is not hep arin sp ecific. Thromb
throm boem bolism w ith fond aparinux after hip fracture surgery: a Haemost 1992;67(5):545–549.
m u lticenter, rand om ized , placebo-controlled , d ouble-blind stud y. Arch 60. Alm eid a JI, Coats R, Liem TK, et al. Red u ced m orbid ity and m ortality
Intern Med 2003;163(11):1337–1342. rates of the hep arin-ind u ced throm bocytop enia synd rom e. J Vasc Surg
35. Knu d son MM, Collins JA, Good m an SB, et al. Throm boem bolism fol- 1998;27(2):309–314, d iscussion 315–316.
low ing m u ltiple traum a. J Trauma 1992;32(1):2–11. 61. Alving BM. H ow I treat hep arin-ind u ced throm bocytop enia and
36. Rogers FB, Strind berg G, Shackford SR, et al. Five-year follow -u p of throm bosis. Blood 2003;101(1):31–37.
prophylactic vena cava filters in high-risk trau m a p atients. Arch Surg 62. Bald w in ZK, Sp itzer AL, N g VL, et al. Contem p orary stand ard s for
1998;133(4):406–411, d iscu ssion 412. the d iagnosis and treatm ent of hep arin-ind u ced throm bocytop enia
37. Streiff MB. Vena caval filters: a com p rehensive review. Blood 2000; (H IT). Surgery 2008;143(3):305–312.
95(12):3669–3677. 63. Greinacher A, Volp el H , Janssens U, et al. Recom binant hiru d in (lep -
38. Osborne N H , Wakefield TW, H enke PK. Venou s throm boem bolism in irud in) provid es safe and effective anticoagulation in patients w ith
cancer patients undergoing m ajor surgery. Ann Surg Oncol 2008;15(12): hep arin-ind u ced throm bocytop enia: a p rosp ective stu d y. Circulation
3567–3578. 1999;99(1):73–80.
39. Bergqvist D, Agnelli G, Cohen AT, et al. Du ration of p rop hylaxis 64. Kovacs MJ. Su ccessful treatm ent of hep arin ind u ced throm bocytop e-
against venous throm boem bolism w ith enoxap arin after su rgery for nia (H IT) w ith fond ap arinu x. Thromb Haemost 2005;93(5):999–1000.
cancer. N Engl J Med 2002;346(13):975–980. 65. Lee AY, Levine MN , Baker RI, et al. Low -m olecu lar-w eight hep arin
40. H ull RD, Raskob GE, Brant RF, et al. Relation betw een the tim e to versu s a cou m arin for the p revention of recu rrent venou s throm -
achieve the low er lim it of the APTT therap eu tic range and recurrent boem bolism in p atients w ith cancer. N Engl J Med 2003;349(2):146–153.
venou s throm boem bolism d u ring hep arin treatm ent for d eep vein 66. van d ongen CJ, Mac Gillavry MR, Prins MH . Once versu s tw ice d aily
throm bosis. Arch Intern Med 1997;157(22):2562–2568. LMWH for the initial treatment of venou s throm boem bolism . Cochrane
41. Dou ketis JD, Kearon C, Bates S, et al. Risk of fatal p u lm onary Database Syst Rev 2003;(1):CD003074.
em bolism in patients w ith treated venou s throm boem bolism . JAMA 67. Merli G, Sp iro TE, Olsson CG, et al. Su bcu taneou s enoxap arin once or
1998;279(6):458–462. tw ice d aily com p ared w ith intravenous u nfractionated heparin for
42. Prand oni P, Lensing AW, Cogo A, et al. The long-term clinical cou rse treatm ent of venou s throm boem bolic d isease. Ann Intern Med 2001;
of acu te d eep venou s throm bosis. Ann Intern Med 1996;125(1):1–7. 134(3):191–202.
43. Bates SM, Ginsberg JS. Clinical p ractice: treatm ent of d eep -vein 68. Gross PL, Weitz JI. N ew anticoagu lants for treatm ent of venou s
throm bosis. N Engl J Med 2004;351(3):268–277. throm boem bolism . Arterioscler Thromb Vasc Biol 2008;28(3):380–386.
44. van Den Belt AG, Prins MH , Lensing AW, et al. Fixed d ose su bcuta- 69. Cap rini JA. The fu tu re of m ed ical therap y for venou s throm boem boli.
neou s low m olecular w eight hep arins versus ad justed d ose u nfrac- Am J Med 2008;121:S10–S19.
tionated heparin for venou s throm boem bolism . Cochrane Database 70. Bu ller H R, Cohen AT, David son B, et al. Id rap arinu x versu s stand ard
Syst Rev 2000(2):CD001100. therapy for venous thromboembolic d isease. N Engl J Med 2007;357(11):
45. Ageno W, Tu rpie AG. Low -m olecu lar-w eight hep arin in the treatm ent 1094–1104.
of p ulm onary em bolism . Semin Vasc Surg 2000;13(3):189–193. 71. Spyrop ou los AC. Investigational treatm ents of venou s throm boem -
46. H u ll RD, Pineo GF, Brant RF, et al. Am J Med 2009;122:762–769. bolism . Expert Opin Investig Drugs 2007;16(4):431–440.
47. Kearon C, Kahn SR, Agnelli G, et al. Antithrom botic therap y for 72. Agnelli G, Gallu s A, Gold haber SZ, et al. Treatm ent of p roxim al d eep -
venou s throm boem bolic d isease: Am erican College of Chest Physi- vein throm bosis w ith the oral d irect factor Xa inhibitor rivaroxaban
cians Evid ence-Based Clinical Practice Gu id elines (8th ed ition). Chest (BAY 59-7939): the ODIXa-DVT (Oral Direct Factor Xa Inhibitor BAY
2008;133(6, Sup p l):454S–545S. 59-7939 in Patients With Acu te Sym p tom atic Deep -Vein Throm bosis)
48. Bu ller H R, David son BL, Decou su s H , et al. Fon d ap arin u x or stu d y. Circulation 2007;116(2):180–187.
enoxap arin for the initial treatm ent of sym p tom atic d eep venou s 73. Bu ller H R, Lensing AW, Prins MH , et al. A d ose-ranging stu d y evalu -
throm bosis: a rand om ized trial. Ann Intern Med 2004;140(11): ating once-d aily oral ad m inistration of the factor Xa inhibitor rivarox-
867–873. aban in the treatm ent of p atients w ith acute sym ptom atic d eep vein
49. Bu ller H R, David son BL, Decou su s H , et al. Su bcu tan eou s fon d a- throm bosis: the Einstein-DVT Dose-Ranging Stu d y. Blood 2008;112(6):
p arin u x versu s intravenou s u n fractionated hep arin in the in itial 2242–2247.
treatm ent of p u lm onary em bolism . N Engl J Med 2003;349(18): 74. Weitz JI, H irsh J, Sam am a MM. N ew anticoagu lant d ru gs: the Seventh
1695–1702. ACCP Conference on Antithrom botic and Throm bolytic Therap y.
50. H yers TM, Agn elli G, H u ll RD, et al. An tith rom botic th erap y Chest 2004;126(3)(Sup p l):265S–286S.
for venou s throm boem bolic d isease. Chest 2001;119(1)(Su p p l): 75. Saiah E, Soares C. Sm all m olecu le coagu lation cascad e inhibitors in
176S–193S. the clinic. Curr Top Med Chem 2005;5(16):1677–1695.
51. Zhu T, Martinez I, Em m erich J. Venou s throm boem bolism : risk factors 76. Greenfield LJ, Proctor MC. Tw enty-year clinical exp erience w ith the
for recu rrence. Arterioscler Thromb Vasc Biol 2009;29(3):298–310. Greenfield filter. Cardiovasc Surg 1995;3(2):199–205.
52. Prand oni P, Lensing AW, Prins MH , et al. Resid u al venou s throm bosis 77. Berry RE, George JE, Shaver WA. Free-floating d eep venou s throm bo-
as a p red ictive factor of recu rrent venou s throm boem bolism . Ann sis: a retrospective analysis. Ann Surg 1990;211(6):719–722, d iscu ssion
Intern Med 2002;137(12):955–960. 722–723.
53. H u ll RD, Mard er VJ, Mah AF, et al. Qu antitative assessm ent of throm - 78. Langan EM III, Miller RS, Casey WJ III, et al. Prop hylactic inferior
bus bu rd en pred icts the ou tcom e of treatm ent for venou s throm bosis: vena cava filters in trau m a p atients at high risk: follow -u p exam ina-
a system atic review. Am J Med 2005;118(5):456–464. tion and risk/ benefit assessm ent. J Vasc Surg 1999;30(3):484–488.
54. Cosm i B, Legnani C, Cini M, et al. D-d im er levels in com bination w ith 79. Su germ an H J, Su germ an EL, Wolfe L, et al. Risks an d benefits of
resid u al venou s obstru ction and the risk of recu rrence after anticoag- gastric byp ass in m orbid ly obese p atients w ith severe venou s stasis
u lation w ithd raw al for a first id iop athic d eep vein throm bosis. d isease. Ann Surg 2001;234(1):41–46.
Thromb Haemost 2005;94(5):969–974. 80. Chiou AC. Bed sid e placem ent of IVC filters. Endovasc Today 2005;4:
55. Palareti G, Cosm i B, Legnani C, et al. D-d im er testing to d eterm ine the 60–63.
d u ration of anticoagu lation therap y. N Engl J Med 2006;355(17): 81. Decousus H, Leizorovicz A, Parent F, et al. A clinical trial of vena caval fil-
1780–1789. ters in the prevention of pulmonary embolism in patients with proximal
deep-vein thrombosis: Prevention du Risque d’Embolie Pulmonaire par 110. Sem ba CP, Dake MD. Iliofem oral d eep venou s throm bosis: aggres-
Interruption Cave Stud y Group. N Engl J Med 1998;338(7):409–415. sive therapy w ith catheter-d irected thrombolysis. Radiology 1994;191(2):
82. Greenfield LJ, Proctor MC. Filter com p lications and their m anage- 487–494.
m ent. Semin Vasc Surg 2000;13(3):213–216. 111. Mew issen MW, Seabrook GR, Meissner MH , et al. Catheter-d irected
83. Joels CS, Sing RF, H eniford BT. Com p lications of inferior vena cava fil- throm bolysis for low er extrem ity d eep venou s throm bosis: rep ort of a
ters. Am Surg 2003;69(8):654–659. national m u lticenter registry. Radiology 1999;211(1):39–49.
84. Prom isloff RA. Pu lm onary em bolism after insertion of a Greenfield 112. Elsharaw y M, Elzayat E. Early resu lts of throm bolysis vs anticoagu la-
filter. J Am Osteopath Assoc 2002;102(10):558–560. tion in iliofem oral venou s throm bosis: a rand om ised clinical trial. Eur
85. Kinney TB, Rose SC, Lim GW, et al. Fatal p arad oxic em bolism occu r- J Vasc Endovasc Surg 2002;24(3):209–214.
ring d uring IVC filter insertion in a patient w ith chronic pu lm onary 113. Meneveau N , Serond e MF, Blond e MC, et al. Managem ent of u nsu c-
throm boem bolic d isease. J Vasc Interv Radiol 2001;12(6):770–772. cessfu l throm bolysis in acu te m assive p u lm onary em bolism . Chest
86. Greenfield LJ, Proctor MC. Recu rrent throm boem bolism in p atients 2006;129(4):1043–1050.
w ith vena cava filters. J Vasc Surg 2001;33(3):510–514. 114. Meissner MH . Throm bolytic therap y for acu te d eep vein throm bosis
87. Henke P, Varma MH, Proctor MC, et al. Suprarenal Greenfield filter and the venou s registry. Rev Cardiovasc Med 2002;3(Su p p l 2):S53–S60.
placement: the Ann Arbor experience. In: Yao JT, Pearce WH, eds. Mod- 115. Sharafu d d in MJ, Su n S, H oballah JJ. End ovascu lar m anagem ent of
ern trends in vascular surgery. St. Louis; MO: McGraw-Hill 2000;427–434. venou s throm botic d iseases of the u p p er torso and extrem ities. J Vasc
88. Marcy PY, Magne N , Frenay M, et al. Renal failu re second ary to Interv Radiol 2002;13(10):975–990.
throm botic com plications of suprarenal inferior vena cava filter in 116. Meier GH , Pollak JS, Rosenblatt M, et al. Initial exp erience w ith
cancer p atients. Cardiovasc Intervent Radiol 2001;24(4):257–259. venou s stents in exertional axillary-su bclavian vein throm bosis. J Vasc
89. Ferris EJ, McCow an TC, Carver DK, et al. Percu taneou s inferior vena Surg 1996;24(6):974–981, d iscu ssion 981–983.
caval filters: follow -u p of seven d esigns in 320 p atients. Radiology 117. Axelrod DA, Proctor MC, Geisser ME, et al. Ou tcom es after su rgery
1993;188(3):851–856. for thoracic ou tlet synd rom e. J Vasc Surg 2001;33(6):1220–1225.
90. H arris EJ Jr, Kinney EV, H arris EJ Sr, et al. Phlegm asia com plicating 118. Turp ie AG. Throm bolytic agents in venou s throm bosis. J Vasc Surg
p rophylactic percu taneou s inferior vena caval interru p tion: a w ord of 1990;12:196.
cau tion. J Vasc Surg 1995;22(5):606–611. 119. Gold haber SZ. Pulmonary em bolism . Lancet 2004;363(9417):1295–1305.
91. Thom as JH , Cornell KM, Siegel EL, et al. Vena caval occlusion after 120. Sharm a GV, Folland ED, McIntyre KM, et al. Long-term benefit of
bird ’s nest filter p lacem ent. Am J Surg 1998;176(6):598–600. throm bolytic therap y in p atients w ith p u lm onary em bolism . Vasc Med
92. MAUDE d atabase. The FDA Web site: w w w.fd a.gov. Up d ated 2003. 2000;5(2):91–95.
93. Schutzer R, Ascher E, Hingorani A, et al. Preliminary results of the new 121. Gold haber SZ, H aire WD, Feld stein ML, et al. Altep lase versu s
6 F TrapEase inferior vena cava filter. Ann Vasc Surg 2003;17(1):103–106. hep arin in acute pulm onary em bolism : rand om ised trial assessing
94. Greenfield LJ, Proctor MC. Vena caval filters for th e p revention of right-ventricular fu nction and p u lm onary p erfu sion. Lancet 1993;
p u lm on ary em bolism . N Engl J Med 1998;339(1):47; au th or rep ly 341(8844):507–511.
47–48. 122. Jerjes-Sanchez C, Ram irez-Rivera A, Arriaga-N ava R, et al. H igh d ose
95. Reekers JA. Re: cu rrent p ractice of tem porary vena cava filter inser- and short-term strep tokinase infu sion in patients w ith pu lm onary
tion: a m ulticenter registry. J Vasc Interv Radiol 2000;11(10):1363–1364. em bolism : p rosp ective w ith seven-year follow -u p trial. J Thromb
96. Poon WL, Luk SH , Yam KY, et al. Mechanical throm bectom y in infe- Thrombolysis 2001;12(3):237–247.
rior vena cava throm bosis after caval filter placem ent: a report of three 123. Konstantinid es S, Geibel A, Olschew ski M, et al. Association betw een
cases. Cardiovasc Intervent Radiol 2002;25(5):440–443. throm bolytic treatm ent and the p rognosis of hem od ynam ically stable
97. Joshi A, Carr J, Chrism an H , et al. Filter-related , throm botic occlu sion p atients w ith m ajor p ulm onary em bolism : resu lts of a m u lticenter
of the inferior vena cava treated w ith a Giantu rco stent. J Vasc Interv registry. Circulation 1997;96(3):882–888.
Radiol 2003;14(3):381–385. 124. Eid -Lid t G, Gasp ar J, Sand oval J, et al. Com bined clot fragm entation
98. Tard y B, Mism etti P, Page Y, et al. Sym p tom atic inferior vena cava fil- and asp iration in p atients w ith acu te p u lm onary em bolism . Chest
ter throm bosis: clinical stu d y of 30 consecu tive cases. Eur Respir J 2008;134(1):54–60.
1996;9(10):2012–2016. 125. Eklof B, Kistner RL. Is there a role for throm bectom y in iliofem oral
99. Wojcik R, Cipolle MD, Fearen I, et al. Long-term follow -u p of traum a venou s throm bosis? Semin Vasc Surg 1996;9(1):34–45.
patients w ith a vena caval filter. J Trauma 2000;49(5):839–843. 126. Ju han CM, Alim i YS, Barthelem y PJ, et al. Late resu lts of iliofem oral
100. Greenfield LJ, Proctor MC, Michaels AJ, et al. Prop hylactic vena caval venou s throm bectom y. J Vasc Surg 1997;25(3):417–422.
filters in trau m a: the rest of the story. J Vasc Surg 2000;32(3):490–495, 127. Patel N P, Labropou los N , Pap p as PJ. Cu rrent m anagem ent of venou s
d iscussion 496–497. u lceration. Plast Reconstr Surg 2006;117(7)(Su p p l):254S–260S.
101. Patton JH Jr, Fabian TC, Croce MA, et al. Prop hylactic Greenfield fil- 128. Beebe-Dim m er JL, Pfeifer JR, Engle JS, et al. The ep id em iology of
ters: acute com p lications and long-term follow -u p . J Trauma 1996; chronic venou s insufficiency and varicose veins. Ann Epidemiol 2005;
41(2):231–236, d iscu ssion 236–237. 15(3):175–184.
102. Cahn MD, Rohrer MJ, Martella MB, et al. Long-term follow -u p of 129. Barw ell JR, Davies CE, Deacon J, et al. Com p arison of su rgery and
Greenfield inferior vena cava filter p lacem ent in child ren. J Vasc Surg com pression w ith com pression alone in chronic venous u lceration
2001;34(5):820–825. (ESCH AR stu d y): rand om ised controlled trial. Lancet 2004;363(9424):
103. Dard ik A, Cam p bell KA, Yeo CJ, et al. Vena cava filter ensnarem ent 1854–1859.
and d elayed m igration: an u nu su al series of cases. J Vasc Surg 1997; 130. Prand oni P, Lensing AW, Prins MH , et al. Below -knee elastic com p res-
26(5):869–874. sion stockings to prevent the post-throm botic synd rom e: a rand om -
104. Wood w ard EB, Farber A, Wagner WH , et al. Delayed retrop eritoneal ized , controlled trial. Ann Intern Med 2004;141(4):249–256.
arterial hem orrhage after inferior vena cava (IVC) filter insertion: case 131. Kakkos SK, Daskalopou lou SS, Daskalop ou los ME, et al. Review on
report and literatu re review of caval p erforations by IVC filters. Ann the value of grad uated elastic com p ression stockings after d eep vein
Vasc Surg 2002;16(2):193–196. throm bosis. Thromb Haemost 2006;96(4):441–445.
105. Raghavan S, Akhtar A, Bastani B. Migration of inferior vena cava filter 132. Bone C. Tratam iento end olu m inal d e las varices con laser d e d iod o:
into renal hilu m . Nephron 2002;91(2):333–335. estu d io p relim inary. Rev Patol Vasc 1999;5:35–46.
106. Porcellini M, Stassano P, Mu su m eci A, et al. Intracard iac m igration of 133. N avarro L, Min RJ, Bone C. End ovenou s laser: a new m inim ally inva-
nitinol TrapEase vena cava filter and p arad oxical em bolism . Eur J Car- sive m ethod of treatm ent for varicose veins—p relim inary observa-
diothorac Surg 2002;22(3):460–461. tions u sing an 810 nm d iod e laser. Dermatol Surg 2001;27(2):117–122.
107. Jackson Slapp y AL, Kenned y RJ, H akaim AG, et al. Delayed tran- 134. Fan CM, Rox-And erson R. End ovenou s laser ablation: m echanism of
scaval renal p enetration of a Greenfield filter p resenting as sym p to- action. Phlebology 2008;23(5):206–213.
m atic hyd ronephrosis. J Urol 2002;167(4):1778–1779. 135. Knip p BS, Blackbu rn SA, Bloom JR, et al. End ovenou s laser ablation:
108. Loehr SP, H am ilton C, Dyer R. Retrieval of entrap p ed gu id e w ire in an venou s ou tcom es and throm botic com p lications are ind ep end ent of
IVC filter facilitated w ith u se of a m yocard ial biopsy forceps and the p resence of d eep venou s insu fficiency. J Vasc Surg 2008;48(6):
snare d evice. J Vasc Interv Radiol 2001;12(9):1116–1119. 1538–1545.
109. Meissner MH , Manzo RA, Bergelin RO, et al. Deep venous insu ffi- 136. Pu ggion i A, Kalra M, Gloviczki P. Su p erficial vein su rgery and
ciency: the relationship betw een lysis and su bsequ ent reflu x. J Vasc SEPS for chronic venou s insu fficiency. Semin Vasc Surg 2005;18(1):
Surg 1993;18(4):596–605, d iscu ssion 606–608. 41–48.
137. Sp arks SR, Ballard JL, Bergan JJ, et al. Early benefits of su bfascial 155. Korn P, Patel ST, H eller JA, et al. Why insu rers shou ld reim bu rse for
end oscop ic p erforator su rgery (SEPS) in healing venou s u lcers. Ann com p ression stockings in p atients w ith chronic venou s stasis. J Vasc
Vasc Surg 1997;11(4):367–373. Surg 2002;35(5):950–957.
138. Kalra M, Gloviczki P. Su bfascial end oscop ic p erforator vein surgery: 156. Blecken SR, Villavicencio JL, Kao TC. Com p arison of elastic versu s
w ho benefits? Semin Vasc Surg 2002;15(1):39–49. nonelastic com pression in bilateral venous ulcers: a rand om ized trial.
139. Jia X, Mow att G, Bu rr JM, et al. System atic review of foam sclerother- J Vasc Surg 2005;42(6):1150–1155.
apy for varicose veins. Br J Surg 2007;94(8):925–936. 157. Pad berg FT Jr. Su rgical intervention in venou s u lceration. Cardiovasc
140. Ceu len RP, Som m er A, Vernooy K. Microem bolism d u ring foam scle- Surg 1999;7(1):83–90.
rotherapy of varicose veins. N Engl J Med 2008;358(14):1525–1526. 158. Taw es RL, Barron ML, Coello AA, et al. Op tim al therap y for ad vanced
141. French LE, Braun R, Masou ye I, et al. Post-strip p ing sclerod erm iform chronic venous insu fficiency. J Vasc Surg 2003;37(3):545–551.
d erm atitis. Arch Dermatol 1999;135(11):1387–1391. 159. Gloviczki P. Subfascial end oscop ic p erforator vein su rgery: ind ica-
142. Rigby K, Palfreym an SJ, Beverley C, et al. Su rgery for varicose veins: tions and resu lts. Vasc Med 1999;4(3):173–180.
u se of tou rniquet. Cochrane Database Syst Rev 2009;(4):CD001486. 160. van Gent BW, H op WC, van Praag MC et al. Conservative versu s su r-
143. Bergan JJ. Varicose veins: hooks, clam p s, and su ction: ap p lication of gical treatm ent of venou s leg u lcers: a p rosp ective, rand om ized , m u l-
new techniqu es to enhance varicose vein surgery. Semin Vasc Surg ticenter trial. J Vasc Surg 2006;44(3):563–571.
2002;15(1):21–26. 161. Delis KT, Bjarn ason H , Wen nberg PW, et al. Su ccessfu l iliac vein
144. Gold m an M. Com plications of sclerotherap y in venou s su rgery. In: and in ferior vena cava sten tin g am eliorates ven ou s clau d ication
Gloviczki P, Yao JST, ed s. Handbook of venous disorders, 2nd ed . Lond on, and im p roves ven ou s ou tflow, calf m u scle p u m p fu n ction , an d clin -
England : H od d ard & Stou ghton; 2001. ical statu s in p ost-throm botic syn d rom e. Ann Surg 2007;245(1):
145. Morrison C, Dalsing MC. Signs and sym p tom s of sap henou s nerve 130–139.
injury after greater sap henou s vein strip p ing: p revalence, severity, 162. N eglen P, H ollis KC, Olivier J, et al. Stenting of the venou s ou tflow in
and relevance for m od ern p ractice. J Vasc Surg 2003;38(5):886–890. chronic venou s d isease: long-term stent-related ou tcom e, clinical, and
146. Criad o E, Lujan S, Izqu ierd o L, et al. Conservative hem od ynam ic su r- hem od ynam ic resu lt. J Vasc Surg 2007;46(5):979–990.
gery for varicose veins. Semin Vasc Surg 2002;15(1):27–33. 163. Knip p BS, Fergu son E, William s DM, et al. Factors associated w ith
147. Scavee V, Theys S, Schoevaerd ts JC. Transillu m inated p ow ered m ini- ou tcom e after interventional treatm ent of sym ptom atic iliac vein
p hlebectom y: early clinical exp erience. Acta Chir Belg 2001;101(5): com p ression synd rom e. J Vasc Surg 2007;46(4):743–749.
247–249. 164. Thorp e P, Osse FS, Dang H P. End ovascu lar reconstru ction for chronic
148. Cheshire N , Elias SM, Keagy B, et al. Pow ered p hlebectom y (TriVex) iliac vein and inferior vena cava obstru ction. In: Gloviczki P, Yao JST,
in treatm ent of varicose veins. Ann Vasc Surg 2002;16(4):488–494. ed s. Handbook of venous disorders, 2nd ed . Lond on, England : H od d ard
149. Chetter IC, Mylankal KJ, H u ghes H , et al. Rand om ized clinical trial & Stoughton; 2001.
com p arin g m u ltip le stab in cision p hlebectom y and transillu m i- 165. Jost CJ, Gloviczki P, Cherry KJ Jr, et al. Su rgical reconstru ction of
n ated p ow ered p hlebectom y for varicose veins. Br J Surg 2006;93(2): iliofem oral veins and the inferior vena cava for nonm alignant occlu-
169–174. sive d isease. J Vasc Surg 2001;33(2):320–327, d iscu ssion 327–328.
150. d e Zeeu w R, Wittens C, Loots M, et al. Transillu m inated p ow ered 166. Bergan JJ, Kum ins N H , Ow ens EL, et al. Su rgical and end ovascu lar
p hlebectom y accom plished by local tu m escent anaesthesia in the treatm ent of low er extrem ity venou s insu fficiency. J Vasc Interv Radiol
treatm ent of tribu tary varicose veins: prelim inary clinical resu lts. 2002;13(6):563–568.
Phlebology 2007;22(2):90–94. 167. Alim i YS, DiMau ro P, Fabre D, et al. Iliac vein reconstru ctions to treat
151. Bergan JJ, Schm id -Schonbein GW, Sm ith PD, et al. Chronic venou s acu te and chronic venou s occlu sive d isease. J Vasc Surg 1997;25(4):
d isease. N Engl J Med 2006;355(5):488–498. 673–681.
152. Kahn SR, Shrier I, Julian JA, et al. Determ inants and tim e cou rse of the 168. Raju S, H ollis K, N eglen P. Obstru ctive lesions of the inferior vena
p ostthrom botic synd rom e after acu te d eep venou s throm bosis. Ann cava: clinical featu res and end ovenou s treatm ent. J Vasc Surg 2006;
Intern Med 2008;149(10):698–707. 44(4):820–827.
153. Labrop oulos N , Waggoner T, Sam m is W, et al. The effect of venou s 169. Sarkar R, Eilber FR, Gelabert H A, et al. Prosthetic rep lacem ent of the
throm bus location and extent on the d evelop m ent of p ost-throm botic inferior vena cava for m alignancy. J Vasc Surg 1998;28(1):75–81, d is-
signs and sym ptom s. J Vasc Surg 2008;48(2):407–412. cu ssion 82–83.
154. Kunimoto BT. Management and prevention of venous leg ulcers: a liter- 170. Bower TC, Nagorney DM, Cherry KJ Jr, et al. Replacement of the inferior
ature-guided approach. Ostomy Wound Manage 2001;47(6):36–42, 44–39. vena cava for malignancy: an update. J Vasc Surg 2000;31(2):270–281.
CHAPTER
32
Complications of
Endovascular Therapy
Matthew J . Eagleton and Sunita D. Srivastava
■ INTRODUCTION The p athogenesis of contrast nep hrop athy is com p lex

and involves a synergistic effect of d irect renal tu bu lar
The nu m ber of p atients u nd ergoing end ovascu lar inter- ep ithelial cell toxicity and renal m ed u llary ischem ia. Three
ventions is increasing. At som e point, m ost surgeons w ill m ain factors contribu te to its d evelop m ent, inclu d ing
manage patients w ho require an end ovascu lar proced u re, osm otic effects, renal hem od ynam ic effects, and renal tu bu -
or they w ill be called on to m anage one of the com p lica- lar effects (3,5). Contrast m ed ia are sm all m olecules that
tions of an intervention. Ou tlined in this chapter are the become concentrated in u rine u p to 100-fold w ithin the first
main com p lications encountered w ith several of the m ost 4 hou rs after ad m inistration. The increase in osm olarity
com m on end ovascu lar therapies. cau ses an increase in intratu bu lar hyd rostatic p ressu re and
d ecreases filtration p ressu re in glom eru li, lead ing to
■ ARTERIAL INTERVENTIONS osm otic d iu resis and increased sod iu m and w ater excre-
tion. The increased sod iu m load to the m acu la d ensa in the
■ Diagnostic angiography d istal tu bu le cau ses a d ecrease in the glom eru lar filtration
A num ber of com plications can occur d uring the perform - rate (6). This resp onse is m ore p ronou nced w ith contrast
ance of rou tine angiograp hy. Most of these comp lications agents that have a high osm olarity com p ared to those that
are not sp ecific to d iagnostic angiography but can occu r are iso-osm olar or hyp o-osm olar. The osmotic d iuresis
d u ring the perform ance of any nu m ber of vascular inter- also p laces an increased m etabolic d em and on the d istal
ventions. More com m on com plications includ e those asso- nep hron and m ay aggravate m ed u llary hyp oxia (7).
ciated w ith the ad m inistration of rad iologic contrast agents Contrast agents can cause d irect cytotoxicity, leading to
and inju ry to the artery u sed for access. contrast nephropathy. Cytotoxicity is suggested by evid ence
of cell inju ry on histologic evalu ation and by the p resence
■ Contrast nephropathy of enzym uria, particularly N-acetyl- -glucosaminid ase and
alkaline phosphatase (8,9).
Contrast nephropathy is the development of acute renal fail- Contrast agents affect renal blood flow in a biphasic pat-
ure or insufficiency secondary to the parenteral administra- tern. Initially, there is a brief increase in renal blood flow, fol-
tion of radiologic contrast agents. Contrast nephropathy is low ed by a stead y d ecline. Decreased blood flow is d u e to
the third leading cause of acute renal failure in hospitalized the ind u ction of renal vasoconstriction cau sed by rheologic
patients (1). The incid ence of contrast nephropathy varies changes, erythrocyte d eformability, and the release of a
widely and depends on the definition of renal insufficiency variety of end othelial factors, includ ing end othelin, ad eno-
used by the varying stud ies (2,3). Contrast nephropathy gen- sine, calcium, and oxygen free rad icals (6,10–12).
erally presents as an elevation in serum creatinine 1 to 2 days Alteration s in ren al fu nction are seen in alm ost every
after dye ad ministration. Creatinine values peak after 3 to p atient w ho receives a contrast load , bu t not every
5 days and return to baseline by 7 to 10 days (2,4). The acute p atient d evelop s contrast nep hrop athy (13). There are a
renal failure is usually nonoliguric in nature. Urinalysis variety of risk factors for d evelop m ent of acu te renal fail-
reveals a range of findings from normal to granular casts, u re follow ing contrast d ye ad m inistration (Table 32.1).
tubular epithelial cells, and protein. The diagnosis of contrast Alone, chronic renal insu fficiency is th e m ost im p ortan t
nephropathy is typically easy to make, given the temporal risk factor; com bined w ith d iabetes m ellitu s, n egative
relationship of the onset of renal failure to the contrast load . effects are synergistic. In on e series of 1,800 p atien ts
Other causes of acute renal failure, such as hypovolemia and u nd ergoing card iac catheterization, the rate of contrast
atheroembolization of the renal arteries, should be excluded. nep hrop athy w as 14.5% for all p atients. Wh en ad ju sted
for th e p resence of risk factors, th e d evelop m en t of con-
Matthew J. Eagleton, Sunita D. Srivastava: Cleveland trast nep hrop athy increases from 1.2% in p atients w ith
Clinic Lerner College of Med icine-CWRU, Dep artm ent of no risk factors to 100% in p atients w ith fou r or m ore risk
Vascu lar Su rgery, Cleveland , OH 44195 factors (14).
367
Table 3 2 . 1 Risk fa ct or s for con t r a st n ep h rop a t hy (PGI2), have attenu ated the rise of seru m creatinine after
contrast ad m inistration (24,25). Their m ajor sid e effects,
Chronic renal insufficiency su ch as hyp otension and nau sea, have lim ited their use.
Diabetes mellitus Contrast m aterial can be rem oved w ith the u se of
Congestive heart failure hem od ialysis, w hich has led som e to qu estion w hether it
cou ld serve to p revent contrast-ind u ced nep hrop athy. The
High dose contrast agent
d ata su p p orting this, how ever, is sp arse, and it is not cu r-
Nephrotoxic drugs (i.e., antibiotics) rently recom m end ed routinely.
Agents that decrease renal perfusion (i.e., NSAIDs)
NSAIDs, nonsteroidal anti-inflammatory drugs. ■ Puncture site complications

The incid ence of p u nctu re site com p lications ranges from
0.3% to 35% (26–32). Low er rates are associated w ith d iag-
Contrast nep hrop athy, d espite generally resolving over nostic p roced u res, w hile higher rates follow interven-
the cou rse of 7 to 10 d ays, is not a benign com plication. Few tional p roced u res d u e to the u se of larger sheaths (33).
patients go on to requ ire d ialysis, but up to 30% w ill have Factors that increase the risk of p u nctu re site com p lica-
resid ual renal im pairm ent and there is som e suggestion tions are significant atherosclerotic d isease in the artery
that p atients affected by contrast nephrop athy have that is being accessed , obesity, and the u se of antithrom -
increased m ortality rates (15,16). Managem ent of these botic or fibrinolytic p harm acotherap ies (30). The m ore
patients is sim ilar to other patients w ho d evelop acu te com p lex the p roced u re, the higher the rate of p u nctu re
renal failu re. A thorou gh investigation should be m ad e to site com p lications (27). In only 9% of all cases is su rgical
id entify contribu ting factors, such as hypovolem ia or therap y necessary (26).
nephrotoxic m ed ications, w ith correction. Monitoring of
seru m chem istries and assessm ent of flu id statu s shou ld Hemorrhage
be perform ed . H em orrhage is the m ost com m on p u nctu re site com p lica-
Although there is no antid ote for the nephrotoxic effects tion, occu rring in 8% of d iagnostic p roced u res and 18% of
of rad iologic contrast m ed ia, several strategies have been arterial interventions (26,28–31). Patients p resent w ith a
d evised w ith the hop e of d ecreasing m orbid ity. N onionic p ainfu l, p u lseless m ass at the p u nctu re site. Assessm ent
and low -osm olality contrast agents w ere d evelop ed to w ith d uplex u ltrasou nd is necessary to exclud e pseu d oa-
low er the com p lications of rad iologic d ye. These agents are neu rysm . H em orrhage m ay not be obviou s on physical
associated w ith a low er incid ence of contrast nephrop athy exam if the bleed ing tracks into the retrop eritoneu m . In
comp ared to high-osm olarity agents (17). Preproced u ral these situ ations, com p u ted tom ograp hy w ill verify the
ad ministration of intravenous flu id is a sim ple, inexp en- d iagnosis. Managem ent entails ap p lication of p ressu re
sive m easu re that treats hyp ovolem ia and shou ld theoreti- over the p u nctu re site follow ed by con tin u ed close obser-
cally offer p rotection to p atients w ho are going to receive vation. If hem orrh age p ersists, su rgical intervention is
rad iologic contrast agents. In ad d ition, it appears that iso- required . Other ind ications for su rgical intervention includ e
tonic 0.9% normal saline is preferable over hyp otonic solu - significant overlying skin changes and hem atom a, cau sing
tions (18). Dop am ine w as thou ght to be protective, given sym ptom atic com p ression of ad jacent nervou s or venou s
its renal vasod ilatory effects, but several stu d ies reveal it to stru ctu res.
have no effect on the d evelop m ent of contrast nep hrop athy
in patients w ith u nd erlying risk factors, and in one stu d y, Pseudoaneurysm
d opam ine increased the risk in d iabetic patients (19,20). Diagnostic proced u res are associated w ith the d evelop-
Similarly, selective d op am ine A 1 agonists, like fenold op am m ent of p seu d oaneu rysm s at the p u nctu re site in 1% of
m esylate (a p otent vasod ilator that increases renal p lasm a p atients having d iagnostic p roced u res and in u p to 5% of
flow ), have failed to provid e significant nephroprotection those u nd ergoing interventions (26,29,30,32,34). Pseud oa-
in larger stu d ies evalu ating nep hrotoxicity (21). Acetylcys- neu rysm s can be d etected by the p alp ation of a p u lsatile
teine is an antioxid ant that has been evalu ated in several m ass on p hysical exam and confirm ed by d u p lex u ltra-
stu d ies for red ucing the incid ence of contrast nephrop athy. sou nd . The m ost com m on anatom ic factor associated w ith
A m eta-analysis of seven rand om ized p rosp ective trials fem oral p seu d oaneu rysm form ation is aberrant p u nctu re,
com p aring orally ad m inistered acetylcysteine w ith hyd ra- entering the vessel in either the external iliac artery or
tion alone have show n it to significantly red uce the risk of su p erficial fem oral artery (35–38). Both these locations
d evelop ing contrast nep hrop athy in p atients w ith u nd erly- m ake com p ression follow ing sheath and catheter rem oval
ing chronic renal insufficiency (22). Most recently, the com - m ore d ifficu lt and less su ccessfu l. The u se of p erip roce-
bination of N -acetyl cysteine (N AC) w ith volu m e d u ral anticoagu lation also increases the risk of p seu d oa-
sup plem entation by sod ium bicarbonate w as found to be neu rysm form ation (32). Sm all p seu d oaneu rysms ( 3 cm )
sup erior to N AC and saline alone (23). Prostagland ins, can resolve sp ontaneou sly, p rovid ed p atients are not anti-
specifically prostagland in E (PGE) and prostagland in I2 coagu lated (32,39).
Chapter 32 • Complications of Endovascular Therapy 369
Persistent pseudoaneurysms and those that cause symp- lary artery and brachial plexus, even a small hematoma can
toms require intervention. Untreated lesions may cause pain, prod uce significant nerve compression. Patients can present
neuropathy, arteriovenous fistulas w ith steal syndrome, or w ith sensory and motor d eficits that can affect the med ian,
rupture. Treatment w as classically performed with surgical rad ial, and ulnar nerve d istribution. This complication
repair, and urgent surgical intervention is recommended occurs in 1% of transaxillary procedures (31). The inci-
w hen there is an expanding pseudoaneurysm, an expanding d ence of femoral neuropathy after a femoral artery puncture
hematoma, severe pain, femoral nerve compression, or groin is 0.2% (44). Femoral neuropathy occurs more frequently
infection (39). When surgical repair is required, management w ith retroperitoneal hemorrhage. Prompt surgical d ecom-
can often be accomplished by lateral suture of the arterial pression is necessary in patients who have neurologic symp-
communication. With large pseudoaneurysms ( 3 cm ), toms to red uce the incid ence of prolonged d eficits (31,44,45).
proximal control of the distal external iliac artery through a
retroperitoneal incision may be required prior to repair. Vascular Closure Device Complications
Recently, nonsu rgical treatm ent of pseu d oaneu rysm s Several d evices have been d evelop ed over the past d ecad e
has p roven effective. Initial exp erience w as w ith u ltra- to assist in arterial p u nctu re site closu re. Approaches
sound -gu id ed com p ression of the p seu d oaneu rysm origin. inclu d e collagen p lu g–m ed iated d evices, su ture-m ed iated
Com p ression is ap p lied for 30 m inutes. Su ccess rates for d evices, and percutaneous placement of metallic “clips” to
comp ression therapy vary and are significantly affected by occlud e the arteriotomy site. These devices have shown to
the p resence of ongoing anticoagulation. In anticoagu lated significantly decrease the amount of time necessary to obtain
patients, failu re rates are as high as 41% (34). When antico- hemostasis (46–48), but there remains some controversy as
agu lation is not present, su ccess rates app roach 90% (40). to w hether they provide an effective reduction in the com-
An alternative is ultrasou nd -gu id ed throm bin injection. p lications associated w ith arterial access. Several reports
This therapy has p roven effective in 90% of p atients, have show n sim ilar com p lication rates com p ared to hem o-
inclu d ing those w ith ongoing anticoagulation (34,41). The stasis obtained by m anu al com p ression (49–52). Som e
m ajor risk of this p roced u re is ind u ction of throm bu s in the investigators have rep orted increased com p lications w ith
native vessel and su bsequ ent occlu sion or d istal em boliza- closu re d evices (53,54), w hile m ore recently, larger ran-
tion. Throm bu s occurs in u p to 3% of patients und ergoing d om ized controlled trials su ggest that closu re d evices m ay
throm bin injection and requires su rgical intervention (34). be associated w ith d ecreased com plication rates for both
The risk ap pears to be red uced if high risk lesions are d iagnostic and interventional p roced u res (55). Com plica-
exclu d ed . These inclu d e pseu d oaneu rysm s com p osed of tions specific to the use of these p ercutaneou s arterial clo-
short, w id e ( 10 m m ) necks and those in small-d iameter sure d evices inclu d e embolization of collagen p lugs,
native arteries. The u se of covered stents has been arterial occlu sion, and infection (56–58). These events occu r
d escribed to treat p ostproced u ral pseud oaneu rysm s, bu t in 2% of d evice d ep loym ents and m ay be red uced if
experience w ith this m od ality is not w id espread (42,43). p rop er p atient selection is em p loyed (58,59).
Arteriovenous Fistula
■ Catheter and guidewire-related complications
The d evelop m ent of an arteriovenou s fistu la com p licates
d iagnostic angiography in 1% of cases and interventional Thrombosis
proced u res in u p to 2% of cases (26,30,31). The incid ence is Arterial throm bosis is rare ( 1% of cases) follow ing both
higher w hen the pu nctu re site is m ore cau d al on the d iagnostic and interventional p roced u res (26,29,30).
fem oral artery, d ue to the ju xtaposition of the su p erficial Throm bosis is affected by the size of the catheter in relation
fem oral artery, d eep fem oral artery, and ad jacent veins in to the size of the arterial lu m en and the length of the
this region. On p hysical exam ination, a bruit w ill be heard catheter exp osed to the blood (60–62). This relationship
over the p u nctu re site, and d uplex ultrasou nd easily con- affects the size of the throm bu s that d evelops on the
firms the d iagnosis. Most arteriovenous fistu lae sp onta- catheter. Throm botic com p lications p resent w ith a variety
neou sly throm bose (32,39). Patients w ith this com p lication of sym p tom s. If the region su p p lied by the occlud ed artery
can be safely m onitored w ith u ltrasound u ntil closure. has a vast collateral blood su p p ly, no significant sym ptom s
Ind ications for intervention inclu d e the d evelop m ent of m ay arise and the only find ing may be loss of d istal palpa-
congestive heart failure d u e to the fistula, limb ischem ia, ble p u lses. This find ing is typ ical of brachial artery throm -
venou s insu fficiency, or d istal em bolization. In these bosis follow ing u p p er extrem ity arterial access. Most
instances, su rgical intervention is w arranted . Em p loying ep isod es of throm bosis are treated w ith thrombectom y, but
covered stents to treat the lesion has been d escribed , bu t if severe u nd erlying atherosclerotic d isease is present, arte-
their u se is not w id espread (42,43). rial byp ass m ay be requ ired .
Neuropathy Arterial Dissection

Nerve injury due to compression from local bleeding is the Arterial d issection is rare, occu rring in 1% of cases
most common and d ebilitating complication after transaxil- (26,29,30). Arterial d issection m ore frequ ently occu rs after
lary arteriography. Because of the close proximity of the axil- interventional p roced u res and w ith antegrad e arterial
punctu res. Occasionally, no intervention is requ ired , esp e- ■ Carotid artery angioplasty and stenting
cially if a retrograd e d issection has occu rred . More severe
Technical Proficiency
d issections present w ith com plete arterial occlu sion and
loss of a p u lse on p hysical exam ination. The su rgical p roce- Carotid p roced u res rep resent a m ore com p lex level of
d u re required to repair these d issections d epend s on the intervention d u e to the d em and ing technical skills
d efect’s extent and location. Short focal lesions can be requ ired for the p roced u re. They inclu d e the fam iliarity
treated by end arterectom y, bu t m ore extensive d issections w ith sm aller p rofile system s, inclu d ing m onorail d elivery
may requ ire arterial bypass. system s, variety of cerebral p rotection d evices, and new
stent p latform s w ith variable d ep loym ent characteristics.
Embolization The op erator m u st be technically facile at intervening
Em bolization com plicates d iagnostic arteriography and from long d istances (fem oral artery to internal carotid
arterial interventions at a rate approaching 6% (26,30). artery), cannu lating a d iseased and friable internal carotid
Em bolization can resu lt from d islod gm ent of atheroem boli artery follow ed by p lacem ent of d istal p rotection d evice,
and the d evelop m ent and em bolization of throm bu s on the balloon angiop lasty, stent d elivery and d ep loym ent, and
introd u cer sheath, and it can involve foreign bod ies su ch as finally cap tu ring the p rotection d evice w ithou t em boliza-
sheared -off p ortions of angiographic catheters. When tion. Several stu d ies have d em onstrated the im p ortance
em bolization occu rs, the su rgeon should consid er inter- of the clinical op erator ’s p roficiency in su ccessfu l carotid
vention to p revent sequ elae. Op tions inclu d e im m ed iate interventions (76,77). Arch anom alies and arch tortu osity
percutaneou s or su rgical throm bectom y (or removal of for- are anatom ic variables that ad d to the com p lexity of the
eign bod y) and selective throm bolysis (45,63,64). Choles- carotid intervention as w ell as higher incid ence of throm -
terol synd rom e is d u e to the d islod gm ent of cholesterol boem bolic com p lications d u e to the m ore extensive
crystals from atherom atous vessels, particu larly the aorta. catheter m anip u lations and d isru p tion of aortic or carotid
Cholesterol em boli lod ge in sm all arterioles and m ost often p laqu es (78).
affect the skin in the form of lived o reticu laris, the kid neys
resulting in renal failu re, and the d igits resu lting in “blu e Stroke
toe synd rom e” (65–67). The incid ence and sequelae of Stroke is the m ost feared com p lication of cerebrovascu lar
em bolization d u ring cerebral angiograp hy and carotid interventions. With the grow ing u se of carotid artery stent-
artery interventions have been extensively stud ied and w ill ing, a m ore thorou gh evalu ation of associated com plica-
be d iscu ssed in m ore d etail below. tions is being realized . The incid ence of cerebrovascular
events follow ing carotid artery stenting varies accord ing
to classification schem es. Events are categorized as m ajor
■ SUPRA-AORTIC INTERVENTIONS strokes, m inor strokes, and TIAs.
Technical success in carotid artery stenting approaches
■ Cerebral angiography 100% (79–83). Thirty-d ay rates of major stroke range from
Many of the com p lications encou ntered w ith cerebral 1.3% to 3.6%, w hile rates of minor stroke and TIA range
angiograp hy are sim ilar to those of routine p eripheral or from 0% to 1.3% and from 3.4% to 10.7%, respectively.
coronary angiograp hy. The consequence of em bolization, Patients w ith severely elevated baseline systolic blood pres-
how ever, is m ore p rofou nd , as the ou tcom e m ay be a cere- sure are at higher risk for hem od ynam ic instability and neu -
bral vascu lar accid ent. Overall com plication rates for cere- rologic events d u ring carotid artery stenting (84).
bral angiography p arallel peripheral angiography and Unfortu nately, it is rare that an op eration can correct
coronary angiograp hy, ranging from 0.6% to 10% (68–71). d istal cerebral em bolization. Distal throm bolysis shou ld be
Com p lications includ e strokes (occu rring at an incid ence of attem p ted if arterial occlu sion is visu alized angiographi-
0.5%) and transient ischem ic attacks (TIAs) (occurring at cally, althou gh it is im p ossible to ascertain w hether the
an incid ence of 0.4%) (71). The incid ence of em bolization occlu sion is second ary to atherom atou s em bolization or
and su bsequ ent cerebral ischem ic event increases if the throm boem bolization. Treatm ent is continu ed u ntil lysis is
patients have sym p tom atic carotid artery stenosis (70,72). achieved , there is system ic evid ence of fibrinolysis, a lim it-
Em bolization d u ring cerebral angiography, how ever, is not ing total d ose of throm bolytic has been d elivered , or p res-
alw ays sym p tom atic. Sou rces of embolization inclu d e ence of intracranial hem orrhage (85).
microscop ic air em bolization or silent throm boem bolism Most carotid artery stent-related strokes are d u e to d is-
(73,74). Bend szu s et al. (75) evalu ated d iffu sion-w eighted tal atheroem boli or throm boem boli d islod ged at the tim e
magnetic resonance im aging before and after angiograp hy of the p roced u re. In ord er to d ecrease the incid ence of
to assess em bolic events in 100 consecu tive patients u nd er- these com p lications, several cerebral p rotection d evices
going d iagnostic angiography. In this stud y, 23% of have been d evelop ed . Several series evalu ating the effi-
patients had evid ence of em bolization w ithou t neu rologic cacy of cerebral p rotection d evices have show n an 80%
sym ptom s. The ap p earance of lesions w as associated w ith red u ction in acu te neu rologic events related to em bolism
d ifficu lt vessel access, higher contrast load s, increased flu o- com p ared to u np rotected p roced u res (86–89). Desp ite the
roscopy tim e, and the use of m u ltiple catheters. u se of em bolic p rotection d evices, how ever, em bolization
has been show n to occu r p ostp roced u rally for u p to Myocardial Infarction and Death
48 hou rs on d iffu sion-w eighted m agnetic resonance im ag- Most p atients w ho u nd ergo carotid artery stenting are con-
ing (90). Cerebral p rotection d evices are also associated sid ered to be at high op erative risk. In one of the first large
w ith com p lications. These com p lications are infrequ ent series, 77% of p atients w ou ld have been ineligible for the
(occu rring 1% of the tim e) and inclu d e focal d issection of N orth Am erican Sym p tom atic Carotid End arterectom y
the internal carotid artery and failu re of d evice d ep loy- Trial d u e to the p resence of m ed ical com orbid ities (99).
m ent. Internal carotid artery vasosp asm occu rs in u p to Inclu d ed in this group of comorbid ities is significant coro-
15% of p atients, half of w hom resp ond to vasod ilatory nary artery d isease, w hich is p resent in 80% of patients in
therap y w ith nitroglycerin (86). In p atients in w hom occlu - som e series (81). Desp ite this level of risk, rates of perioper-
sive p rotection d evices are u sed (i.e., balloon occlu d ers ative m yocard ial infarction w ere only 0% to 0.6% (80,82).
and flow reversal system s), transient alterations in m ental The 30-d ay d eath rates have been rep orted to be betw een
fu nction are d ocu m ented in 15% of p atients (91). This 0% and 4.5% (60,76,83,100–102). The m ajority of d eaths
intolerance to flow arrest is typ ically resolved w ith the w ere related to p erip roced u ral m yocard ial infarction, fatal
restoration of intracranial flow (92). The p roxim al occlu - stroke, or intracranial hem orrhage.
sion and flow reversal system has had few er rep orts of
cerebral hyp op erfu sion (93). Local vessel interaction w ith Restenosis and Late Stroke
the d ep loyed p rotection d evice can also resu lt in com p lica-
The natu ral history of in-stent restenosis is unknow n. A
tions. Intim al d am age d u e to oversizing of the p rotection
restenosis rate follow ing carotid artery stenting has been
d evice, sp asm , and em bolization arou nd the d evice can
rep orted to be 3% at 1 year (103). Tw o typ es of restenosis
resu lt in em bolic and throm botic consequ ences (94). In
have been d escribed : narrow ing w ithin the stent and steno-
ad d ition, excessive d ebris cap tu red w ithin the d evice from
sis at the end of the stent, often cau sed by a kink in the
excessive balloon d ilation or bu lky d isease m ay resu lt in
artery. Most restenoses are treated w ith another stent or
failu re of collap se of the d evice for retrieval. Manip u la-
balloon angiop lasty, w ith one-third d evelop ing rep eated
tions of the d evice w ithou t sheath p rotection m ay resu lt in
ep isod es of recu rrent stenosis. Several stu d ies have u sed
entanglem ent w ith the stent stru ts, d etachm ent of the
life-table analysis to d eterm ine long-term restenosis and
filter, and p otential conversion to op en carotid end arterec-
stroke-free rates. Lal et al. (104) rep orted an in-stent
tom y. Early recognition of cerebral p rotection d evice p rob-
restenosis rate (restenosis d efined as 80% stenosis) of
lem s and trou bleshooting are critical to p revent
6.4% at 60 m onths. Over half of these occu rred at 15, and
conversions and throm boem bolic events. Avoid ance of
none w ere associated w ith neu rologic d eficits. H obson et
overd ilation w ith balloon angiop lasty, asp iration of the
al. (83) rep orted a sim ilar tim e p eriod of recu rrent steno-
fu ll filter basket, m aintenance of system ic anticoagu lation,
sis. Investigators have rep orted an 89% freed om from
and sheath access in the com m on carotid artery m ay
stroke rate at 48 m onths w ith a recu rrent stenosis rate of
red u ce retrieval p roblem s.
45% (105). At m ost institu tions, asym p tom atic p atients
Hemodynamic Instability w ho d evelop a restenosis 80% or sym p tom atic p atients
w h o d evelop a resten osis 50% are con sid ered for rein-
Carotid artery angiop lasty and stenting involves d ilation
tervention. Reintervention can entail angiop lasty, angio-
of the carotid bu lb. This m aneuver can cause imm ed iate
p lasty w ith a cu tting balloon, rep eat carotid artery stenting,
card iovascu lar hem od ynam ic alterations, sim ilar to the
and carotid artery resection w ith interp osition graft
blood p ressu re and heart rate changes associated w ith
(81,103, 106).
carotid end arterectom y. In the review by Ohki et al. (95),
nearly one-third of patients had an alteration in heart rate.
Ten p ercent of the patients had transient asystole, w hile ■ Brachiocephalic angioplasty and stenting
20% d evelop ed transient brad ycard ia (95). Ap proxim ately
30% d evelop ed concom itant hypotension, half of w hom Embolization and Stroke
requ ired infu sion of phenylep hrine. All und erw ent m oni- The incid ence of acu te cerebral ischem ia follow ing su bcla-
toring in an intensive care unit. Recently, H obson et al. (96) vian artery intervention is low. In one series, there w as only
pu blished the lead -in phase d ata for the Carotid Revascu - one incid ence of TIA in 76 interventions (107). The risk of
larization End arterectom y versu s Stenting Trial (CREST) vertebral artery em bolization is alm ost negligible d ue to
trial and rep orted higher rates of com p lications in carotid the “d elay” phenom enon d escribed by Ringelstein and
stenting w ith increasing age from stroke and d eath. Octo- Zeu m er (108). Follow ing p roxim al su bclavian artery angio-
genarians w ere at highest risk w ith a 12.1% 30-d ay stroke p lasty, the reversal of flow from retrograd e to antegrad e
and d eath rate from carotid stenting and w ere rep orted to d oes not occu r im m ed iately bu t grad u ally. Distal em boliza-
have higher incid ence of hem od ynam ic instability d uring tion involving the brachial artery and left internal m am -
the p roced u re. Maintenance of ad equ ate intravascu lar vol- m ary artery has been rep orted in 1.1% of p atients (109).
um e, vasop ressor use, and avoid ance of overd ilation w ith Brachial artery em bolization can be easily m anaged w ith a
balloon angiop lasty and oversized stents m ay red u ce this brachial artery cu td ow n and em bolectom y. Em bolization
com p lication (84,97,98). to the left internal m am m ary artery m ay have a profound
effect in patients w ho have had coronary artery bypass stent infection is u nknow n, bu t it w as hyp othesized that
grafting. Patients m ay experience acute m yocard ial infarc- p rolonged fem oral access and an infected left arm venou s
tion and corresp ond ing hem od ynam ic com prom ise. Treat- access contribu ted to stent infection.
ment is generally catheter-d irected throm bolytic therapy.
Although com m on carotid angiop lasty and stenting has Mortality
been reported with success by several investigators (109,110), Mortality rates from brachiocep halic interventions are
higher risks of embolization and stroke have been docu- low, rep orted at 0% to 4.8% (107,109,111,115). Deaths in the
mented in cases of combined common carotid artery stenting im m ed iate p ostp roced u ral p eriod (30 d ays) have rarely
and standard carotid bifurcation end arterectomy (109). been attribu table d irectly to the end ovascu lar p roced ure. In
a few cases, d eaths w ere d u e to strokes that occu rred at the
Technical Complications tim e of angiop lasty and stent p lacem ent (109). Long-term
Technical com p lications have been d escribed in 11% of m ortality tend s to be u nrelated to the brachiocep halic d is-
patients u nd ergoing treatm ent of subclavian artery steno- ease bu t related to coexisting or su bsequ ently d evelop ed
sis or occlu sion (107,109,111). These com plications inclu d e com orbid ities.
stent m igration, failu re to cross the occlusive lesion, arterial
d issection, acu te throm bosis, arterial ru pture, and inad ver- Restenosis and Occlusion
tent covering of the vertebral artery. Arterial d issection is Immed iate success in the treatment of subclavian artery
treated by p lacem ent of a stent. Acu te throm bosis is treated stenosis is between 95% and 100% (107,111,115,116). Angio-
w ith locally d elivered throm bolysis and su bsequ ent bal- plasty alone has a lower success rate (80% to 85%) compared
loon angiop lasty. Arterial ru pture is one of the m ost feared to primary arterial stenting (97% to 100%) (107,111,116,117).
com plications of end ovascular therap ies. Ru ptu re is Complete occlusion of the vessel and lesions 2 cm correlate
d etected by visualization of contrast extravasation on com - w ith lower success rates. Short-term patency (1 year) is lower
pletion angiogram . Prom pt recognition is im portant in in patients who have undergone only angioplasty (76%)
ord er to avoid exsangu inations or lim b loss. An angio- compared to patients receiving primary stenting (95%) (116).
plasty balloon can be reinserted and inflated at the site of Longer-term outcomes (4 years) favor primary angioplasty,
ru pture, p rovid ing a tam ponad e effect (112). Prolonged w ith a patency rate of 68% compared to a primary patency
balloon inflation m ay be sufficient to provid e hem ostasis rate stenting of 59%. This difference w as due to the develop-
and no fu rther intervention m ay be necessary. If balloon ment of in-stent stenosis. The d evelopment of restenosis can
inflation fails, a treatm ent option is p lacem ent of a covered be due to misplacement of the stent, particularly in ostial
stent to exclu d e the artery’s ru ptured area. This m aneu ver lesions. Up to half of patients who develop a restenosis
has proven effective in the treatm ent of a variety of bra- become symptomatic (107). Restenosis can be treated, when
chiocephalic inju ries and is associated w ith shorter op era- necessary, by balloon angioplasty.
tive tim es, less blood loss, and equivalent p atency rates
com pared to op en su rgery (113).
N ot all subclavian artery ruptu res follow ing percu ta-
■ AORTOILIAC INTERVENTIONS
neous translu m inal angioplasty (PTA) or stent placem ent ■ Aortoiliac angioplasty and stenting
are im m ed iately id entified . Disru ption m ay present in a
d elayed fashion in the form of a pseud oaneu rysm. This Technical Complications
com plication m ay present w ith symp tom s d u e to comp res- Iliac artery PTA and stent p lacem ent is technically success-
sion on su rrou nd ing stru ctu res, inclu d ing the recu rrent fu l in 95% and 97% of p atients, resp ectively (118). Stenotic
laryngeal nerve (hoarseness), sym pathetic chain (H orner segm ents are m ore effectively treated than occlu sions.
synd rom e), and brachial plexu s (w eakness or paresthe- Technical com p lications occu r in 6% of interventions and
sias). Althou gh an end ovascu lar ap proach m ay be effective inclu d e su bintim al d ilation, d issection, arterial ru pture,
at am eliorating the p seud oaneu rysm , sym p tomatic lesions inability to cross the lesion, and d istal em bolization. In one
are best treated w ith op en su rgery to accom plish aneu rys- series, 2.8% d evelop ed com p lications requ iring su rgery
mal d ecom pression. and 0.9% requ ired reconstru ctive byp ass (119). Clinically
significant d istal em bolization occu rs in 1% of patients
Stent Infection u nd ergoing iliac artery PTA and stent p lacem ent. Dopp ler
One incid ence of su bclavian artery stent infection has been u ltrasound has d etected silent peripheral em bolization in
d escribed in the literatu re (114). The patient p resented w ith 90% of p atients follow ing iliac PTA (120). Sym p tom atic
Staphylococcus aureus bacteremia and stigm ata of septic em bolization can be treated by a variety of end ovascu lar
em boli to the ip silateral hand 6 d ays after stent placem ent. m ethod s, inclu d ing su ction throm bectom y and throm -
CT evalu ation revealed a phlegm on surround ing the bolytic therap y. If these m od alities are not su ccessfu l, surgi-
stented p ortion of the artery; angiograp hy d etected a cal throm boem bolectom y is necessary.
pseu d oaneu rysm at the site. The p atient u nd erw ent resec- Iliac artery d issection d u ring PTA is rep orted in 0.5% to
tion of the affected p ortion of the artery w ith au togenou s 1% of p atients (105,121). H alf of these p atients d evelop ed
vascu lar reconstru ction. The und erlying etiology of the significant lu m inal com p rom ise. Dissections can be treated
be punctured percutaneously with a 21-gauge needle,

d epend ing on the balloon’s location and its relationship to
surround ing structures.
The exact incidence of iliac stent migration is not know n,
and this is not a frequently reported complication. Migration
is probably not an uncommon complication that occurs
w hen a self-expand ing stent abruptly jumps cranially upon
d eployment (126). Movement may not cause significant
m orbid ity, bu t it m ay resu lt in the com p lete d islod gm ent
of the stent. Unfortunately, once these stents have been
d eployed , they are d ifficult to retrieve. Management options
for this complication includ e em ergent vascular surgery,
observation, stent retrieval using end ovascular snares and
large introducer sheaths, and aortoiliac bifurcation recon-
struction using balloon-expand able stents.
FIGURE 32.1. Angiogram from a patient undergoing iliac artery angioplasty
that resulted in a perforation. This is demonstrated by the arrow. The hemor- Infection
rhage was controlled by brief occlusion of the perforation site with an angio-
plasty balloon and subsequent placement of an iliac artery stent. Stent infection follow ing iliac artery stent placem ent is rare
bu t has been rep orted to occu r both acutely and in a
d elayed fashion after several years (127–129). In one case,
by prolonged balloon inflation to tack d ow n the flap or by after throm bolytic therap y and su bsequ ent iliac artery
placem ent of an intra-arterial stent. If end ovascu lar ther- stent p lacem ent, the p atient d evelop ed fever, groin p ain,
apy is not su ccessful, operative treatm ents inclu d e iliac and ip silateral low er extrem ity p etechiae (128). The patient
end arterectom y, iliofem oral bypass, fem oral—fem oral d evelop ed sym p tom s of system ic inflam m atory resp onse
byp ass, and aortobifem oral byp ass grafting. Arterial d is- w ith evid ence of m u ltisystem organ failu re, and Staphylo-
section has been reported in 10% of patients und ergoing coccus aureus grew from blood cu ltu res. Treatm ent su bse-
iliac artery stent placem ent; 70% of the d issections cau se qu ently requ ired excision of the stent and the involved
hem od ynam ically significant stenosis requ iring an ad d i- segm ent of artery, follow ed by above-the-knee am putation.
tional stent p lacem ent (122). Another rep ort d escribes a sim ilar clinical scenario (129).
Vessel injury is related to balloon oversizing and to the The resected iliac artery revealed severe necrotizing arteri-
degree of arterial calcification. Iliac artery rupture during bal- tis, and cu ltu res grew S. aureus and S. epidermidis. Disru p-
loon dilation and stent placement has been reported in 0.9% tion and fracture of the arterial intim a and m ed ia d uring
of cases (123,124). Vessel disruptions can present w ith uncon- angiop lasty m ay p red isp ose this p ortion of the artery to
tained hemorrhage, contained hemorrhage, or pseudoa- seed ing by bacteria. Bacteria have been show n to colonize a
neurysm formation (Fig. 32.1). The key to initial management stent surface irreversibly and to prevent tissu e incorpora-
is maintenance of endovascular access across the site of dis- tion (130). N o stu d ies have exam ined the efficacy of
ruption with a guidew ire. Control of hemorrhage can be p erip roced u ral antibiotic p rop hylaxis, bu t given the seri-
obtained with the insertion of an angioplasty balloon to tam- ou sness of stent infection, m any au thors ad vocate antibi-
ponad e the site of injury. If prolonged balloon tamponade otic u se.
does not achieve hemostasis, the placement of a covered stent
can be used to seal the injury. Uncontrolled hemorrhage war- Restenosis
rants emergent surgical intervention, but balloon occlusion Restenosis follow ing iliac artery PTA occu rs in 5% to 11% of
proximal to the site of injury can afford some time to prepare p atients. The incid ence of recu rrent stenosis and the d evel-
for surgery. Risk factors for rupture are similar to those for op m ent of recu rrent sym p tom s d ep end on the ind ication
dissection and include the presence of a high-grad e stenosis for the p rim ary intervention (118,131). Patients treated for
with heavy calcification. Other risk factors include the use of lim b salvage have higher restenosis and sym p tom recu r-
oversized balloons and manual inflation without manomet- rence rates than those treated for clau d ication. Outcom es
ric control. are im p aired by you ng age and the p resence of poor d istal
Other complications of iliac artery PTA and stent place- ru noff (131,132). Fou r-year p rim ary p atency rates for iliac
ment includ e nond eflating angioplasty balloons and stent PTA are 65% for stenosis and 54% for occlu sion in patients
migration. Mod ern angioplasty catheters are very reliable, w ith clau d ication and 53% for stenosis and 44% for occlu -
but d espite many safeguard s, d eployment failures can occur. sion in those w ith lim b-threatening ischem ia (133). In a
The most common cause of failure of angioplasty balloons is m eta-analysis evalu ating ou tcom es of iliac artery PTA and
kinking or plugging of the d eflation lumen (125). Injection of stent p lacement in 1,300 p atients, 4-year p rim ary patency
carbon d ioxid e or saline can clear the d eflation lumen. In rates w ere 77% for stenotic lesions treated w ith iliac stent-
add ition, a fine wire can be inserted through the inflation ing and 61% for occlu sive lesions in p atients w ith claud ica-
lumen. If these techniques are not successful, the balloon can tion and w ere 67% for stenotic lesions treated w ith iliac
stenting and 53% for occlu sive lesions in patients w ith follow in g rep erfu sion of isch em ic lim bs, an d contrast
lim b-threatening ischem ia (133). The risk of long-term fail- reaction.
ure w as red u ced by 39% after stent placem ent com pared to
PTA alone. Desp ite this, lim b salvage rates are reported as
high as 97% in follow -u p (134). Iliac artery stent patency
■ Aortic endografts for aneurysmal disease
rates are significantly low er in w om en and in p atients w ith Iliac Artery Rupture
renal insu fficiency, d iabetes, and / or critical ischem ia The p rim ary m od e of p lacem ent of aortic end ografts is
(134,135) bu t d o not appear to be affected by TransAtlantic via a fem oral artery cu td ow n an d d ep loym en t of grafts
InterSociety Consensus (TASC) classification (134). throu gh th e iliac artery system an d in to the aorta. Dis-
Late iliac artery thrombosis can d evelop in 10% of ease, su ch as ath erosclerosis, or tortu osity can lead to
patients (122). Most of these lesions can be treated w ith com p lication s involving th e iliac artery d u ring p lace-
throm bolytic therap y follow ed by rep eat angiop lasty of in- m ent. If th e d elivery system u sed to p lace th e end ograft
stent restenosis or end ovascu lar or su rgical therap y for is significan tly larger th an the iliac artery, the vessel can
more d istally occlu sive lesions. Patency is reported to be ru p tu re d u ring p lacem ent. Iliac artery ru p tu re has been
87% at 1 year (136). Prosp ective stu d ies reveal that elevated rep orted in 1% to 2% of cases (139,140). Several m an eu -
plasm a fibrinogen levels are a m ajor risk factor for arterial vers can be u sed to traverse com p lex iliac arteries. Iliac
throm bosis and iliac artery stent restenosis (137). artery stenosis can be p red ilated w ith balloon angio-
p lasty to allow safe p assage of the d elivery system . Pre-
Mortality p roced u ral sten tin g of th e iliac arteries is gen erally
Mortality rates follow ing PTA and stenting of the iliac d issu ad ed as it m akes p lacem en t p roh ibitive. If tortu ou s
artery are low and ran ge from 0% to 1.2% (119,123,138). iliac arteries are p resen t, th e u se of a stiff gu id ew ire m ay
Som e m ortalities have been d irectly attribu table to the h elp red u ce the tortu osity and allow easier access (Fig.
intervention. These inclu d e d eaths from overw helm ing 32.2). In som e in stan ces, th e u se of tw o stiff gu id ew ires
cholesterol em bolization, the d evelop m ent of sep ticem ia (also know n as a “bu d d y w ire”) m ay straighten the
A B
FIGURE 32.2. Angiogram from a patient undergoing

endograft repair of an abdominal aortic aneurysm. A: The
preoperative study revealed tortuous iliac arteries (arrow ).
B: Placement of a “floppy” guidewire allows the iliac
C artery to retain a tortuous course (arrow ). C: Placement
of a stiff wire causes the iliac artery system to straighten.
tortu osity. If these techniqu es d o not allow ad equ ate Table 3 2 .2 Typ es of en d olea k s
p lacem en t of the end ograft, an iliac artery cond u it can be
u sed . This techniqu e involves the su tu ring of a p rosthetic Type I Inadequate sealing at either the proximal aortic
graft to the m id com m on iliac artery. The end ograft is or distal iliac landing zones. Allows antegrade
or retrograde flow into the aneurysm sac.
p laced throu gh th e p rosthetic graft and com m on iliac
artery, an d th e iliac lim b of the graft is seated in th e p ros- Type II Patent aortic branch vessel (i.e., lumbar artery)
thetic graft. The d istal lim b of the p rosthetic graft is then providing retrograde flow into the aneurysm sac.
an astom osed to the com m on fem oral artery. The d istal Type III Defects in the fabric of the graft or at the junc-
end of the com m on iliac artery is oversew n to allow ret- tion zone between modular components provid-
rograd e flow throu gh the external iliac artery and into ing flow into the aneurysm sac.
the hyp ogastric artery. Type IV Diffuse leaking of blood between the inter-
stices of the fabric or where the graft is sutured
Pelvic Ischemia to the stents.
Iliac artery aneu rysm s coexist w ith abd om inal aortic Type V(controversial) Aneurysm sac pressurized and enlarges despite
aneu rysms (AAAs) in up to 30% of patients u nd ergoing no identifiable blood flow into the sac.
end ograft rep air (141–145). This circum stance can p resent a
problem w ith aortic end ograft placem ent, as the iliac arter-
ies m ay be too large for the iliac lim bs to form a seal. In
these situ ations, the iliac lim b of the aortic end ograft may attachm ent sites. Typ e II end oleaks (Fig. 32.4) arise from
be p arked in the external iliac artery, covering the hyp ogas- p atent aortic branch vessels. Su ch vessels inclu d e p atent
tric artery. If this is a planned event, the hyp ogastric artery lu m bar arteries or the inferior m esenteric artery. These
is often em bolized preoperatively to cause its occlusion allow retrograd e flow into the AS, continu ed p ressu riza-
and p revent an end oleak. The presence of an internal iliac tion, and p otential risk for ru p tu re. Typ e III end oleaks
artery aneu rysm w ou ld necessitate the sam e treatm ent. d evelop from d efects in the fabric of the graft or at the
Rarely, bilateral hypogastric artery embolization is required, ju nction zone betw een m od u lar com p onents (Fig. 32.5).
usu ally p erform ed in a staged fashion.
Com plications from hypogastric artery em bolization
can occu r in u p to 50% of patients (142). Bu ttock clau d ica-
tion is the p red om inant com p laint after hyp ogastric artery
occlu sion. Bu ttock clau d ication occurs in 12% to 50% of
patients, bu t few have sym ptom s that persist beyond sev-
eral m onths (141–145). Up to 25% of m en com plain of new
onset erectile d ysfunction (144,145). Significant p elvic
d evascularization lead ing to colonic ischem ia requiring
bow el resection is of theoretical concern, bu t this entity has
not been d escribed in any of the larger series. Patients
requ iring em bolization of the m ore d istal branches of the
hyp ogastric artery are at a higher risk of d eveloping p elvic
sym p tom s (146). Bilateral hypogastric artery em bolization
has not been associated w ith increased sym ptom s w hen
com p ared to u nilateral em bolization (142,143,145). Coil
em bolization of the hypogastric artery can be avoid ed alto-
gether if it is not aneurysm al. If as little as 5 m m of norm al
d iam eter com m on iliac artery is present p rior to its bifu rca-
tion and there is 15 mm of acceptable artery d istal to the
bifu rcation, coil em bolization of the internal iliac artery is
not necessary in ord er to obtain a d istal iliac artery seal
(147).
Endoleaks
An end oleak is the p ersistence of blood flow ou tsid e of
the end ograft w ithin the aneu rysm sac (AS) (148).
End oleaks are classified accord ing to their etiology. Five
typ es of end oleaks have been d escribed (Table 32.2)
(149,150). A typ e I end oleak (Fig. 32.3) arises from inad e- FIGURE 32.3. Aortogram demonstrating a type I endoleak. The white arrow
demonstrates the lateral aspect of the stent graft. The black arrow points to
qu ate sealing at either the p roxim al aortic (allow ing ante- contrast leaking around the proximal seal of the endograft, filling the
grad e flow ) or d istal iliac (allow ing retrograd e flow ) aneurysm sac.
FIGURE 32.4. CT scan demonstrating a type II endoleak. GL

represents the graft limbs, and AS is the aortic sac. There is
contrast outside the graft limbs within the aneurysm sac that
is characteristic of a type II endoleak (EL). This patient had
an expanding aneurysm, and selective angiography revealed
a patent inferior mesenteric artery. This artery was embolized
and there was subsequent regression of the aneurysm size.
Typ e IV end oleaks d evelop second ary to d iffu se leaking

of blood betw een the interstices of the fabric or w here the
graft is su tu red to a stent. Typ e V end oleaks occu r w hen
the AS rem ains p ressu rized and the aneu rysm enlarges,
bu t no flow can be d em onstrated w ithin the AS u sing cu r-
rently available im aging m od alities. A typ e V end oleak is
one in w hich the d efect is large enou gh to allow blood
flow into the sac and to transm it p ressu re to the sac, bu t
the exit site is not p resent or too sm all to be d etected by
conventional im aging techniqu es (151).
Typ e I and typ e III end oleaks are associated w ith a sig-
nificant risk of aneu rysm enlargem ent and p ossible ru p -
tu re. These end oleaks shou ld be treated if they are
d etected (152,153). Treatm ent m ay be accom p lished by the
p lacem ent of ad d itional end ograft com p onents, inclu d ing
a p roxim al aortic extension cu ff or an ad d itional iliac lim b.
If the leak is a p roxim al typ e I end oleak and the graft is
ju xtap osed to the inferior bord er of the renal arteries, a
large balloon-exp and able stent can be p laced in the p roxi-
m al asp ect of the end ograft to increase rad ial force, cau s-
ing better ju xtap osition of the graft to the aortic w all. If
less-invasive interventions are u nsu ccessfu l at treating
these typ es of end oleaks, rem oval of the end ograft w ith
conventional su rgical rep air is ind icated . Fabric tears are
easily m anaged if the site of the leak is localized . This com -
p lication can be m anaged by p lacem ent of an aortic cu ff or
an iliac extension to cover the hole. If the leak is m ore d if-
fu se, the entire end ograft can be relined or the d evice can
be exp lanted .
Typ e II end oleaks are rarely associated w ith aneu rysm
FIGURE 32.5. Aortogram demonstrating a type III endoleak (EL). This
patient had a homemade graft inserted that was of aorto-uni-iliac design. ru p tu re (154). At least 10% to 15% of p atients w ill be id enti-
There is an occluding stent in the contralateral iliac artery (OS) with a fied w ith a typ e II end oleak d u ring the end ograft’s lifespan
femoral–femoral bypass graft (FF). The patient presented 5 years after the (155–158). Chronic anticoagu lation therap y is not associ-
initial graft insertion with back pain and acute expansion of the aneurysm
ated w ith an in creased risk of typ e II en d oleak form ation,
sac (AS). Aortogram reveals a leak from the body of the graft (EL) filling
the AS. The endograft was relined with a new graft that sealed the bu t typ e II leaks are less likely to sp ontaneou sly resolve if
endoleak. the p atient requ ires w arfarin (159). N o intervention is
generally und ertaken w hen a typ e II end oleak is d iagnosed tain p atency w hile 44% of u nsu p p orted lim bs required this
unless it is associated w ith an increase in aneu rysm size or d egree of intervention (173). Oversizing of the graft lim b
associated w ith aortic p u lsatility on p hysical exam ination. also increases the risk of throm bosis. The infold ing of the
In these situ ations, arteriograp hy is requ ired to id entify graft m aterial d u e to the oversizing d ecreases the inner
the sou rce of the end oleak. An aortogram is p erform ed , d iam eter, w hich increases the incid ence of throm bosis
follow ed by selective injections into each iliac lim b, the (174). Extension of the iliac lim b into the external iliac
su p erior mesenteric artery, and hypogastric arteries. Super- artery m ay p lace the lim b at increased risk of throm bosis
selective arterial access is then obtained , w hich allow s d u e to size m ism atch betw een the graft and the sm aller
em bolization of the feed ing vessels. Alternatively, d irect sac external iliac artery. Dam age to the external iliac artery or
punctu re can be perform ed w ith embolization of the feed - fem oral artery at the tim e of graft p lacem ent (i.e., d issec-
ing vessels (160). The sac is then filled w ith glue, coils, or tion) can su bsequ ently cau se an ou tflow obstru ction and
other em bolization m aterial. graft lim b thrombosis (171).
Managem ent of p atients w ith lim b throm bosis d ep end s
Endograft Structural Failure on the severity of the ind u ced ischem ia. N early one-third
One of the m ost w orrisom e long-term com p lications asso- of p atients p resent w ith m ild sym p tom s and requ ire no
ciated w ith aortic end ografting is m aterial failure. Stru c- intervention (172). Most p atients, how ever, present w ith
tu ral failu re is d ifficu lt to id entify as p atients are often more severe ischemia and require a femoral—femoral bypass
asym p tom atic and m ay not present w ith acute changes. in ord er to rep erfu se the affected lim b. Few p atients are
Three m od es of stru ctu ral failu re have been d escribed in su ccessfu lly treated w ith throm bolysis or graft throm bec-
aortic end ografting, involving fabric erosion, su tu re d is- tom y follow ed by end ovascu lar rep air. Most ep isod es of
ru ption, and m etal fractu re (161). The d evelop m ent of graft lim b throm bosis p resent w ithin the first 6 m onths;
end oleaks second ary to graft erosion has been d ocu m ented no lim b occlu sions have been d escribed after 30 m onths
in first-generation grafts (Fig. 32.5) (162,163). Areas of graft (171–173,177).
erosion are hyp othesized to be second ary to the interaction
of the stent m aterial w ith the fabric. Repeated aortic p u lsa- Graft Migration
tions cau se friction betw een the stent and the fabric, cau s- Distal stent-graft m igration com plicates abd om inal aortic
ing eventual graft d eterioration and the d evelopm ent of a end ografting in 9% to 45% of p atients. Migration is a risk
typ e III end oleak. In m any aortic end ografts, the graft for d evelop ing a typ e I end oleak and d elayed ru p tu re or
material is attached to a m etal skeleton w ith su tu res. In late conversion to op en rep air (178). The p athophysiology
several series in w hich p atients d evelop ed new end oleaks, of end ograft m igration is com p lex, bu t blood flow is the
a graft exp lantation sutu re d isrup tion w as d iscovered m ain d isp lacing force (179). As the tu be of the end ograft
w ithin the graft (164,165). The m echanism lead ing to cu rves, the change in velocity of the blood cau ses an
sutu re d isru p tion is sim ilar to graft erosion. It is not increase in the d isp lacem ent force. Resistance to m igration
know n, how ever, if suture d isruption d irectly lead s to is afford ed by friction betw een the graft and the aortic w all
end ograft failu re or if the resu ltant d estabilization of the and by the graft’s colu m nar strength. Barbs or hooks
graft resu lts in further d eterioration. encom p assed in graft d esign m ay p rovid e som e ad d itional
The m ost com m on stru ctu ral p roblem id entified w ith p rotection (180).
aortic end ograft system s has been m etallic stent fractu re Angu lation of the aortic neck m ay d ecrease the frictional
(166). Jacobs et al. (166) reported the ou tcom e of 686 force and increase the risk of graft migration (178,181).
patients w ho u nd erw ent end ovascu lar aneu rysm rep air. Other hypotheses about the cause of d evice migration have
Sixty p atients had m aterial failu re. Three-fourths of these focused on the morphologic changes in the aneurysm and
failu res w ere d u e to m etallic stent fracture. Metal failu re aortic neck after end ovascu lar AAA repair. Aortic neck d ila-
w as cau sed by tw o p rocesses: stress fatigu e and m etal cor- tion, longitu d inal sac shrinkage, and graft shortening have
rosion. Stress fatigu e resu lted from repeated aortic p u lsa- been d escribed (182–185). The aortic neck has been d ocu-
tions. Metal corrosion occu rs pred om inantly in nitinol mented to significantly d ilate d uring the first 2 years after
stents (167). More recent stent-graft d esigns have im p roved end ograft rep air (186). In a review in w hich the incid ence
nitinol p rocessing and d o not exhibit the sam e extent of of graft m igration w as 15%, the tw o ind ep end ent risk fac-
corrosion (168–170). tors for end ograft m igration w ere neck d ilation follow ing
repair and a baseline AAA size of 55 m m . Others have
Limb Thrombosis argu ed that neck d ilation is not a significant event if ad e-
End ograft lim b throm bosis after end ovascular aortic end o- qu ate graft oversizing w as p erform ed at initial end ograft
grafting occu rs in 11% of patients (171–176). A variety of p lacem ent (187).
factors have been hypothesized to place patients at
increased risk for lim b throm bosis. The lack of m etallic Technical Complications and Conversion to Open Surgery
sup p ort w ithin the lim bs of end ografts has been su ggested Technical complications have been d escribed in up to one-
to increase risk for throm bosis. In one series, 5% of su p - fourth of end ograft p lacem ents (188). The occu rrence of crit-
ported lim bs requ ired a su bsequent intervention to m ain- ical events is ind epend ent of operator experience, perhaps
reflecting the fact that more anatomically d ifficult cases are going a secondary intervention died, and this mortality rose
attem pted w ith increasing experience (189). Deployment to 18% if a transabdominal approach w as necessary (177).
d ifficulties includ e graft foreshortening necessitating the
placement of additional distal covered extensions, suprarenal Thoracic Aortic Stent Graft
graft displacement, infrarenal graft displacement, and device- The use of thoracic aortic stent grafts (thoracic endovascular
related issues such as iliac limb kinking or twisting. Conver- aortic repair [TEVAR]) to treat thoracic aortic aneurysm,
sion to open surgery has been reported in only 1% to 3% of w hile early in its com m ercialization, has becom e m ain-
patients during endograft repair (153,158,190,191). According stream. Many of the acu te com p lications associated w ith
to the Eurostar registry, however, 18% of patients with endo- p lacem ent of the thoracic aortic stent grafts are the sam e as
graft placement required a secondary intervention (192). Most those encountered w ith placem ent of abd om inal grafts.
of these interventions (76%) were through a transfemoral N eurologic complications are one of the most concerning
approach, while the rest required a transabdominal (12%) or complications associated w ith TEVAR. During placement of
extra-anatomic (11%) approach. The rates of freedom from the thoracic stent graft, there is w ire, catheter, and device
intervention at 1, 3, and 4 years were 89%, 67%, and 62%, manipulation within the aortic arch, which can lead to cere-
respectively. Other large series have mirrored these results bral embolization and stroke. Stroke rates occur in 3% to 5%
(175,177). of patients undergoing TEVAR, and it occurs more readily in
those patients in w hom the stent graft is placed proximal to
Aneurysm Rupture the left subclavian artery (196). Another catastrophic neuro-
The risk of ru p tu re follow ing aneurysm repair is low. One logic complication associated w ith thoracic aortic surgery is
series reports a freedom from risk of rupture of 98.7% at the development of paraplegia, and TEVAR is not immune
2 years (193). In another series the risk of rupture approached to this complication. TEVAR, how ever, is associated w ith
1% per year (158). The presence of an endoleak and the d evel- low er rates of paraplegia w hen com pared to conventional
opment of graft migration increase the risk of subsequent surgery (6.2% vs. 13%, p 0.007) (197). The primary factor
AAA ru pture. associated w ith the d evelopment of spinal cord ischemia is
the extent of the aorta covered w ith the stent graft (198). Pro-
Mortality tective measures, such as maintaining ad equate blood pres-
Aortic endograft repair of AAA is associated w ith a low mor- sure and spinal fluid drainage, may help to protect against
tality rate in the range of 1% to 3% (153,158,177,191). Most this devastating complication.
deaths are related to cardiovascular morbidity. Two large ran- Stent collapse is another complication that appears to be
domized, prospective trials have compared outcomes of more significant in thoracic aortic stent grafting compared
endovascular aneurysm repair (EVAR) w ith those of conven- w ith EVAR. This occu rs w hen thoracic aortic stent grafts are
tional open surgery for AAA. These studies have demon- p laced in you ng p atients w ho have acu te angulation of the
strated that EVAR is associated with lower perioperative aortic arch and have aortic d iameters that are significantly
mortality rates compared to open surgery (1.7% and 1.2% vs. sm aller than available stent grafts. This scenario typically
4.7% and 4.6%) (194,195). The survival advantage, however, occu rs in the setting of trau matic aortic transection. When
is lost at long-term follow -up with 2-year and 4-year mortal- the stent grafts are oversized and placed in an acu te angu la-
ity rates being similar between the tw o groups (2-year: 11% tion, like the aortic arch, they are p rone to kink or com p ress,
vs. 11% and 4-year: 26% vs. 29%). More patients undergoing resu lting in acu te aortic occlusion, or a fu nctional aortic
EVAR (41%), however, required an additional intervention coarctation (Fig. 32.6). This comp lication is usually treated
during the follow-up period, compared to only 9% of the sur- w ith extra-anatomic bypass to the great arch vessels and
gical arm (194). The need for further interventions, even if extension of the end ograft land ing zone more proxim ally
performed percutaneously, has been associated with an into a straighter portion of the aorta. Alternatively, arch
increased mortality. In one series, up to 8% of patients und er- replacem ent m ay be necessary. The d evelopm ent of m ore
FIGURE 32.6. CT scan from a patient that

was treated with a thoracic aortic stent
graft for a traumatic aortic dissection. The
available graft was significantly larger than
the aortic diameter, and it did not accommo-
date the acute aortic arch angulation. This
resulted in a kinked thoracic aortic endo-
graft (A, arrow). Distal to the kink, the graft
was not able to fully expand (B, arrow ) and
the patient had a function aortic coarcta-
tion. The lesion was treated with an extra-
anatomic bypass to the great arch vessels
and subsequent extension of the endograft
into a more suitable landing zone. A B
ad vanced end ografting systems, and app ropriate d evice (203,205,206). In all cases of early mortality, d eath w as attrib-
sizing, w ill help to avoid this complication. utable to bow el ischemia. Five-year survival rates approach
End oleaks also com p licate TEVAR and are classified in 70% and d o not d epend on w hether the patients underw ent
a sim ilar fashion (Table 32.2). End oleak rate after TEVAR primary PTA or stenting, the number of mesenteric vessels
has been rep orted from 4% to 26% (197,199,200), and by treated , or w hether the superior mesenteric artery, specifi-
life-table analysis, 90% of patients w ill be free from p ri- cally, had an intervention performed upon it (203).
mary end oleak d u ring 30 m onths of follow -u p (201).
End oleaks tend to be m ore type I and type III leaks, w ith
few er typ e II leaks (202). AS enlargem ent is m ore com m on ■ Renal artery angioplasty and stenting
in stent graft treatm ent of thoracic aneurysm s and has been Technical Complications
rep orted in 7% to 14% of patients at 1 year (202). Long-term
Renal artery stenting is associated w ith technical su ccess
d ata for this com p lication, how ever, is lacking given the
rates betw een 91% and 98% (208,209). Com p lications
relative im m atu rity of the p roced u re.
associated w ith renal artery PTA and stenting inclu d e
As the u se thoracic aortic end ograft increases and larger
renal artery ru p tu re (1.7%), aortic d issection at the level of
volu m es of long-term d ata becom e available, a m ore thor-
the renal artery (2.2%), flow -lim iting renal artery d issec-
ou gh u nd erstand ing of the long-term com p lications w ill be
tion (1.1%), and renal artery throm boem bolism (1.1%)
assessed .
(208). Renal artery ru p tu re, if d iagnosed at the tim e of
occu rrence, can be m anaged w ith reversal of anticoagu la-
■ Mesenteric artery angioplasty and stenting tion and tam p onad e of the ru p tu re site w ith inflation of
Technical Complications an angiop lasty balloon. Ru p tu re is not alw ays id entified
at the tim e of the p roced u re and m ay p resent in a d elayed
Primary technical success for mesenteric interventions has
fashion w ith hyp otension, d rop in hem atocrit, and the
been reported at 63% to 81% for PTA and 96% to 100% for
d evelop m ent of a p erinep hric hem atom a on im aging
primary stenting, with overall clinical success (as measured
stu d ies. Dep end ing on the p atient’s hem od ynam ic stabil-
by resolution or significant reduction in symptoms) in up to
ity, the d elayed d iagnosis of renal artery ru p tu re m ay
88% of patients (203–205). Unsuccessful PTA is managed
requ ire no fu rther intervention. In cases of u ncontrolled
w ith subsequent stent placement. In one series, 50% of the
hem orrhage or failu re of less-invasive therap ies, op erative
immediate clinical failures were due to misdiagnosis of
rep air of the ru p tu red renal artery is requ ired . Treatm ent
chronic mesenteric ischemia, and in the follow -up period ,
m ay requ ire a sim p le arterial rep air, arterial reconstru c-
underlying gastrointestinal cancer was identified (203). Clin-
tion, or nep hrectom y.
ical success was not attributable to the number of mesenteric
Renal artery d issection can be m anaged by p lacem ent
vessels that w ere treated. Complications described at the site
of ad d itional stents if d issection involves the m ain renal
of PTA includ e arterial d issection, w hich is managed w ith
artery. When the d issection involves a branch vessel, the
placement of a stent in some cases and observation alone in
p roblem becom es m ore d ifficu lt to m anage and m ay resu lt
others (204). Episod es of postproced ural bow el ischemia
in infarction of the p ortion of the kid ney su p p lied by that
have been d escribed, affecting 7% to 8% of patients undergo-
branch. Renal artery throm bosis and em bolism m ay be
ing mesenteric artery endovascular therapy (206,207). The
treated w ith su ction throm bectom y or the ad m inistration
etiology of this complication, presumed to be embolization,
of a throm bolytic agent. Som e instances of acu te renal
dissection, or the underlying reason for mesenteric interven-
artery throm bosis d u ring the p roced u re requ ire acu te su r-
tion, has not been explained .
gical revascu larization (209). Stent d islod gm ent has been
Restenosis rep orted in 2% of p atients u nd ergoing renal stent p lace-
m ent (210). Tw o-third s of these p atients requ ired abortion
Approximately 15% to 20% of patients w ho have had a su c-
of the end ovascu lar p roced u re and conversion to su rgical
cessful end ovascular mesenteric intervention have recur-
rep air. The others had the stents retrieved w ith the u se of
rent symptoms, generally occurring w ithin the first year
an end ovascu lar snare. Failu re to u se a gu id ing sheath has
(203–206). In most cases, recurrent symptoms are d ue to the
been id entified as a risk for stent d islod gm ent d u ring
d evelopment of restenosis, w hich can be treated w ith repeat
p lacem ent.
PTA and , if necessary, second ary stent placement. Primary
and assisted p rimary patency rates for mesenteric stent
placement have been reported to be 70% and 90%, respec- Renal Function Complications
tively, at 18 months (205). If end ovascular therapy continu es Ap p roxim ately 6% to 25% of p atients u nd ergoing renal
to fail, surgical revascularization should be performed — artery PTA and stent p lacem ent have an elevation in
provid ed the p atient is an acceptable op erative cand id ate. seru m creatinine lasting 30 d ays (208,209). Over half of
these p atients requ ired hem od ialysis, bu t not all requ ired
Mortality long-term d ialysis. The etiology of acu te renal failure is
Mortality rates associated w ith m esenteric PTA and stent variable and in som e instances is d u e to d istal renal artery
placement have been reported to be betw een 0% and 11% em bolization or branch vessel throm bosis resulting in renal
infarction. Renal infarction has been d ocu m ented in 3% ■ LOWER EXTREMITY INTERVENTIONS
of p atients.
■ Femoropopliteal angioplasty and stenting
Infection Technical Complications
Stent infections are not common complications. Several inci- Initial technical success of fem oropopliteal PTA is betw een
dences of renal artery stent infection have been d escribed 76% and 95% (217–221). Failu re is m ainly attributable to
(211–213). The com m on bacteria in all th ese cases w as the inability to cross occlu sions and tight stenoses, inability
S. aureus, bu t in tw o of the case rep orts, at least one ad d i- to inflate the angiop lasty balloon, or inability to enter the
tional bacterium w as isolated from blood cultures, includ ing p atent d istal lu m en. Early failu res 24 hou rs occu r in 23%
Proteus mirabilis and Klebsiella pneumoniae. Risk factors for the of p atients (218).
development of renal artery stent infection do not d iffer Com plications occurring d uring PTA inclu d e arterial
from risk factors for all stent infections. These includ e breaks d isru p tion, throm bosis, d istal em bolization, and arterial
in sterile technique, repeated puncture of the same vessel for d issection. Com p lications occu r m ore frequ ently in
arterial access, reuse of an indw elling catheter, increased fem orop op liteal interventions com p ared to iliac artery
procedure time, and puncture site hematoma formation interventions (13% of cases), and half of these com plica-
(186). Patients present w ith fever, local pain, and leukocyto- tions are significant enou gh to requ ire op eration, transfu-
sis. If bacteremia is associated w ith a particularly virulent sion, or an extend ed hosp ital stay. Arterial d isru ption can
pathogen, patients may present w ith a profound systemic p resent w ith the d evelop m ent of hem atom a, pseud oa-
inflammatory response manifested by hypotension, tachy- neu rysm , or arteriovenou s fistu la. Managem ent includ es
card ia, and multisystem organ failure. An intrarenal abscess reversal of anticoagulation and the use of a balloon catheter
m ay form d u e to em bolization from the infected sten t. to occlu d e the arterial inju ry. The u se of covered stents has
CT scans are sensitive for the d iagnosis of stent infection and been d escribed to effectively treat this com p lication (222).
show an intense inflammatory response around the affected Operative intervention m ay be requ ired if bleed ing is not
stent and renal artery. Renal artery pseud oaneurysm forma- controlled .
tion is associated w ith the renal artery stent infection Em bolization can occu r from throm bu s or atherom a-
(212,213). Death second ary to overw helming infection has tou s d ebris from d isru p ted p laqu e. Treatm ent involves the
been described as a result of renal artery stent infection (213). ad m inistration of catheter-d irected throm bolytic therapy
Treatm ent involves intravenous antibiotic ad ministration or su rgical throm boem bolectom y (Fig. 32.7). Acu te throm -
and resuscitation guided by the clinical scenario. Resection bosis at the angiop lasty site has been d escribed in 2.5% of
of the infected stent is m and atory, inclu d ing rem oval of p atients and generally occu rs at sites of p laque u lceration
su rrou nd ing infected and d evitalized tissu e. Excision is (219). As w ith em bolization, throm boses are generally
follow ed by autogenous renal artery reconstruction. Some treated w ith throm bolytic therap y and , if not su ccessful,
interventionalists recommend the routine use of prophylac- op en throm bectom y. Arterial d issection can also occu r fol-
tic antibiotics prior to renal PTA and stenting (212). low ing PTA. This com p lication is often treated w ith the
p lacem ent of an intra-arterial stent (Fig. 32.8). Most of the
Restenosis com p lications related to PTA are best m anaged by arterial
Follow -up angiography is not routine after renal artery PTA byp ass. Com p lication rates d ep end on the ind ication for
or stenting. Patients are reevaluated if they d evelop w orsen- intervention and the p atient’s age. Old er p atients and those
ing renal fu nction or hypertension. In one series, 20.5% of w ho w ere treated for limb-threatening ischem ia have
patients d eveloped w orsening renal fu nction or hyp erten- w orse ou tcom es.
sion after initially having a positive clinical response to Technical su ccess follow ing fem orop op liteal artery
end ovascu lar therap y (209). When these cases und erw ent stenting is rep orted to be 92% (223). In one series, 27% of
angiography, 14 of the 15 p atients had evid ence of signifi- cases of fem orop op liteal recanalization w ere com p licated
cant in-stent restenosis. H alf of these lesions w ere success- by im m ed iate throm bosis requ iring throm bolytic therapy
fully treated w ith either angioplasty alone, repeat stent (224). One-fifth of these p atients cou ld not have p atency re-
placement, or open su rgery. The other half had no interven- established . Distal em bolization has been rep orted in 10%
tion, as the d egree of restenosis w as 50%. Other series of the p atients and is treated as ou tlined earlier (225).
have reported restenosis rates ranging betw een 11% and
44% at 2 years (214,215). Restenosis is second ary to either Patency and Amputation
intim al hyperplasia or p rogression of atherosclerosis. Prim ary p atency rates for fem orop opliteal interventions
have been rep orted as 43% to 58% at 1 year, 41% to 46% at 2
Mortality years, 38% to 41% at 3 years, and 26% to 38% at 5 years
Thirty-d ay m ortality rates follow ing renal artery PTA and (218–220,226–228). Several factors have been show n to
stent are low, betw een 0% and 1.4% (208–210,216). Mortal- affect ou tcom e of fem orop op liteal angiop lasty. The length
ity has not been d irectly associated w ith the renal artery of the lesion has a negative effect on long-term patency.
intervention, bu t to com plications from com orbid ities. Lofberg et al. (228) evalu ated ou tcom es of 92 p atients w ho
A B C
FIGURE 32.7. A: Lower extremity angiogram revealing the outflow tract of a patient with a more proximal popliteal artery stenosis.
B: This lesion underwent primary balloon angioplasty. Postprocedure ankle-brachial index measurements were significantly lower than
those taken before the procedure. C: Repeat angiography revealed a thromboembolus occluding the outflow tract. Attempts at thrombol-
ysis were unsuccessful and the patient underwent popliteal thromboembolectomy.
und erw ent 121 PTA p roced ures. They reported a p rim ary faired better than those w ith lim b-threatening ischem ia
patency at 5 years of only 12% in those w ith occlusions 5 cm (226). The qu ality of ou tflow also affects ou tcom e (220). The
and 32% in those w ith occlu sions 5 cm . Sim ilar resu lts occu rrence of a com p lication at the tim e of initial PTA also
w ere fou nd by Matsi et al. (227), but they had som e su ccess ad versely affects long-term resu lts. Lim b salvage is 86% to
w ith PTA of lesions up to 10 cm in length. Others have 91% at 5 years.
show n that treatm ent of p atients w ith stenoses faired better In-stent restenosis, as evalu ated by intravascu lar ultra-
than those w ith occlusions, and those w ith clau d ication sou nd , is cau sed by neointim al hyp erp lasia and stent
FIGURE 32.8. A: Angiogram of a

patient who underwent balloon
angioplasty of a popliteal artery
stenosis. This resulted in an arterial
dissection that occluded flow in the
vessel. B: Placement of an intra-
arterial stent successfully treated
the dissection.
A B
remod eling, lead ing to lumen area red uction (229). The ■ Tibial angioplasty and stenting
extent of changes is most significant at stent ed ges. Patency
may be improved by the use of expand ed polytetrafluo- Few stu d ies p rovid e enou gh d ata to ad equ ately evalu ate
roethylene (ePTFE) stent-graft relative to bare stents (230). com p lications follow ing end ovascu lar intervention in the
Saxon et al. (230) reported the largest experience as part of a tibial arteries. Technical su ccess has been d escribed in 87%
US m ulticenter, prospective, rand om ized trial of PTA ver- to 92% of p atients (235,236). Com p lications related to tibial
sus PTA and ePTFE-covered stents. The total number of PTA inclu d e the need for em ergency vascu lar su rgery
patients treated w as only 28, w ith 13 patients receiving PTA (0.7% of p atients), p roced u rally related d eaths (0.4%),
alone and 15 patients rand omized to PTA and covered stent am p u tation (0.4%), and the d evelop ment of com partment
placement. At 2-year follow -u p, primary patency in the cov- synd rom e after tibial recanalization (0.4% of cases) (235).
ered stent group w as 87%, w hereas in the PTA alone grou p, Lim b salvage w as rep orted in 91% of these lim bs, but 5-
it w as only 25% (p 0.002). Further investigation is cer- year su rvival w as only 31%. The tw o largest series reported
tainly w arranted into the application of this technology. In on the ou tcom es of tibial PTA w ere rep orted by Faglia et al.
ad d ition, d rug-elu ting stents are being investigated for the (236) in 2002 and by Dorros et al. (235) in 2001. Faglia et al.
treatment of femoropopliteal d isease. One such stud y eval- rep orted on the ou tcom es of 191 tibial PTA p roced u res per-
uated the use of sirolimu s-elu ting stents (231). Sirolimu s form ed in p atients w ith critical lim b ischem ia (rest p ain or
acts as an anti-inflammatory and cytostatic antiproliferative tissu e loss). Clinical recu rrence occu rred in 7.3% of
agent that d iminishes smooth muscle cell proliferation, p atients at a m ean tim e to recu rrence of 4.6 m onths. The
w hich may prevent the d evelopment of neointimal hyper- m ajority of these recu rrences w ere su ccessfu lly treated
plasia. Du d a et al. (231) reported on the ou tcome of 36 w ith rep eat angiop lasty. Major am p u tation w as requ ired
patients recru ited for the participation in a rand omized , in only 5.2% of p atients. Dorros et al. rep orted on the ou t-
d ouble-blind , prospective trial evaluating d rug-eluting com e of 270 PTA p roced u res in p atients w ith critical lim b
stents versus uncoated stents in the treatment of ischem ia. Over a 5-year follow -u p , only 8% requ ired a su b-
femoropopliteal occlusive d isease. The in-stent mean lumen sequ ent su rgical revascu larization and only 9% requ ired a
d iameter w as significantly larger in the sirolimus-eluting m ajor am p u tation. Su rvival, how ever, w as only 56% at 5
stent grou p compared w ith the uncoated stent at 6 months. years. In som e centers, tibial PTA for isolated tibial lesions
Long-term patency rates are not yet know n, and further is being consid ered as the p rim ary intervention p rior to
investigation w ith this stent, as w ell as others, is und erw ay. tibial artery byp ass, p articu larly in p atients w ith m u ltip le
Alternatives to PTA and stenting have been d eveloped com orbid ities.
for percu taneous intervention of the low er extrem ity arte- More recently, Giles et al. (237) rep orted the resu lts
rial tree, sp ecifically u tilizing d ebu lking technologies. infrap op liteal angiop lasty in 176 lim bs from 163 p atients.
Mechanical atherectom y u ses either a rotational blad e or a In this series, technical su ccess w as achieved in 93% of the
“plane”-like d evice that shaves the atherosclerotic d ebris cases. At 1 and 2 years, p rim ary p atency w as 53% and
from the arterial w all. Most of the resu lts for these d evices 51%, resp ectively, w hile freed om from second ary resteno-
is presented in sm all retrospective series or registry d ata, sis and reintervention w ere 63% and 61%, resp ectively.
w ith the p rim ary end p oint evalu ated often being freed om Patients w ith less severe and less extensive d isease faired
from target vessel revascu larization. Zeller et al. (232) better than those w ith m ore extensive d isease. As more
reported a 76% technical success rate w ith these d evices exp erience is gained w ith this p roced u re, a better und er-
(d efined as obtaining 30% resid ual stenosis). Over half of stand ing of its outcom es and its potential applications w ill
these lesions, however, required adjunctive balloon angio- be attained .
plasty or stent placement. The majority of data, however,
come from the self-reported multicenter Treating Peripherls
with SilverHaw k: Outcomes Collection (TALON) registry
■ Thrombolysis
(233). Similar to other series, there was 74% technical success Throm bolytic therap y is u sed to treat acu te arterial or
rate, but only one-quarter required an adjunctive procedure. venou s occlu sions. The m ain risk associated w ith throm -
Freedom from target vessel revascularization was 80% at 12 bolytic therap y is bleed ing. A variety of agents is u sed for
months. Multiple lesions and increasing Rutherford stage throm bolytic therap y, inclu d ing strep tokinase d eriva-
were predictors of less-favorable outcomes. tives, u rokinase com p ou nd s (UK), tissu e p lasm inogen
activator, and its recom binant form s (rt-PA). An analysis
Mortality of d ata collected in a p rosp ective sin gle-in stitu tion reg-
Mortality rates after fem orop op liteal intervention are low, istry revealed an overall com p lication rate of 55.9% in
ranging betw een 0% and 4.3% (217,220,223,227). Deaths are p atien ts u n d ergoin g th rom bolytic th erap y for both arte-
often related to com orbid ities, but d eath from com p lica- rial an d venou s d isease (238). In p atients receiving
tions d irectly related to end ovascu lar therap y has been th rom bolytic therap y for arterial d isease, com p lications
d escribed , inclu d ing retrop eritoneal hem orrhage (234). inclu d ed d evelop m ent of hem atom a or p seu d oaneu rysm
Su rvival rates at 5 years are 51% to 73%, w ith at least a 6% (30.6% UK vs. 57.7% rt-PA), bleed ing requ iring transfu -
per year m ortality. sion (11.9% UK vs. 18.7% rt-PA), and intracranial bleed ing
(0.8% UK vs. 3.3% rt-PA). Mortality rates w ere 2.9% for shou ld be d iscontinu ed . If necessary, throm bolytic agents
UK and 1.6% for rt-PA. can be reversed w ith cryop recip itate, fresh frozen p lasm a,
In p atients being treated for venou s d isease, the com p li- tranexam ic acid , am inocap roic acid , or ap rotinin. These
cations rep orted w ere hem atom a form ation (18.4% UK vs. interventions are rarely necessary, as m ost throm bolytic
28.6% rt-PA) and bleed ing requ iring transfusion (14.3% UK agents have short half-lives in the range of m inu tes.
vs. 42.9% rt-PA). There w ere no episod es of intracranial
bleed ing in venou s patients, but m ortality rates w ere 2%
for UK com p ared to 19% for rt-PA. The cau ses of m ortality ■ VENOUS INTERVENTIONS
w ere not rep orted in the venou s grou p, bu t in the arterial
grou p , som e w ere related to the d evelopm ent of intracra- ■ Vena cava filters
nial hem orrhage. There are few er com plications w ith the Technical Complications
use of throm bolytic therapy to treat venou s d isease, and
Com p lications d u ring p lacem ent of an inferior vena cava
there ap p ears to be few er com p lications w ith the u se of UK
(IVC) filter are rare. Problem s can inclu d e bleed ing,
com pared to rt-PA.
em bolism, inability to insert the d evice, m isp lacem ent,
Tw o m ajor rand om ized p rosp ective trials have evalu -
m igration, and gu id ew ire entrap m ent. Em bolism is a rare
ated the u se of throm bolytic therap y for low er extrem ity
occu rrence, bu t it can occu r if the d evice is inserted through
ischem ia: Surgery versu s Throm bolysis for Ischem ia of the
d eep venou s throm bosis. If it is su sp ected that throm bus is
Low er Extrem ity (STILE) (239) and Throm bolysis or
lining the IVC or involves both of the iliac veins, an alterna-
Perip heral Artery Surgery (TOPAS) (240). In these trials,
tive approach places the filter through the internal ju gular
com p lications occu rred w ith an incid ence of 22% to 41%
vein. Occasionally, IVC filter p lacem ent is hind ered by d if-
and inclu d ed hem orrhage, d istal em bolization, and
ficu lty in passing the filter throu gh the iliac venous system .
catheter-related problems. Life-threatening hem orrhage
This problem is particu larly d ifficu lt for the left iliac
occu rred in 6.2% of patients u nd ergoing throm bolytic ther-
venou s system . With new er d elivery system s that provid e
apy in the STILE trial and in 12.5% of patients treated w ith
a low er p rofile and increased flexibility, this com plication is
throm bolytics in the TOPAS trial. The TOPAS trial d id
rare.
show that w hen asp irin and therap eu tic hep arin w ere
Acute m igration of IVC filters occurs w hen there is lack
w ithheld d u ring thrombolytic therapy, the rate of intracra-
of ap p osition to the caval w all w ith cranial d isplacem ent.
nial hem orrhage d ecreased from 5% to 0.5% (208). Aggres-
Possible m echanism s for this com plication inclu d e the
sive control of hypertension is also beneficial in d ecreasing
d ep loym ent of the filter into throm bu s, p reventing the lim b
the risk of intracranial hem orrhage (241). Distal em boliza-
from attaching to the caval w all or p lacem ent in an IVC
tion occu rred in 14% of cases. Embolization is generally
that is larger than the filter (242). Few IVC filters are
self-lim iting; as the throm bolysis progresses, the em boliza-
ap p roved for p lacem ent in vena cavas 28 m m , making
tion is cleared . Em bolization requ iring su rgery occu rs in
this an im p ortant anatom ic characteristic to id entify. Filter
2% of cases.
m igration (m ovem ent of 10 m m ) has been d escribed in
In ord er to m inim ize the risks of throm bolytic ther-
30% to 76% of filter p lacem ents (243). Im proved stent
ap y, several criteria h ave been accep ted as con traind ica-
d esigns have low ered this risk to betw een 3% and 10%. In
tions (Table 32.3). The u se of m icrop u nctu re need les and
som e instances, the d evice fails to op en at the tim e of
sm all catheters m ay d ecrease the risk of bleed ing com p li-
release. This p henom enon has been d escribed in 2% to 42%
cations. Monitoring of laboratory valu es, su ch as fibrino-
of cases, d ep end ing on the brand of filter u sed (242,244).
gen level, have been of no valu e in p red icting w hich
Migrated filters can occasionally be left in p lace, or they
p atien ts are at increased risk of bleed in g (241). In the
m ay be snared and rem oved throu gh a large sheath, often
p resence of hem orrhage, hep arin and th rom bolytic agent
requ iring a vein cutd ow n for com plete rem oval.
Table 3 2 . 3 Con t r a in d ica t ion s t o Postdeployment Complications

t h rom bolyt ic t h er a py Excessive tilt of a filter is another p otential com p lication.
Failu re to ad equ ately locate the renal veins p rior to p lace-
Absolute Contraindications m ent increases the risk of this com p lication as filter stru ts
Stroke or transient ischemic attack within the past 2 months
lod ged in the orifice of a branching vein w ill offset the fil-
Gastrointestinal bleeding within the past 10 days
ter ’s alignm ent. Excessive filter tilting increases the risk of
Neurosurgery or intracranial trauma within the past 3 months
su bsequ ent p u lm onary em bolism (245). If a filter is tilted
Relatively Major Contraindications by 14 d egrees, a second filter shou ld be p laced above the
Cardiopulmonary resuscitation within the past 10 days
level of the initial filter.
Major nonvascular surgery or trauma within the past 10 days
Recu rrent pu lm onary em bolism is one of the m ost seri-
Uncontrolled hypertension
Intracranial tumor ou s com p lications of filter p lacem ent, rep orted in 2% to 5%
Recent eye surgery of Greenfield filters (242). This com p lication is m ost often
seen in patients w ho have a malignancy and rem ain w ith a
hyp ercoagu lable state. In 1% to 2% of patients, the filter occu rred in p atients w ho had a history of p reviou s p u l-
traps a m assive throm bu s, filling the volu me of the filter m onary em bolism , w ho had elevated p u lm onary artery
w ith clot and lead ing to IVC occlusion. These patients can p ressu re su ggestive of chronic p u lm onary em bolism , or
present w ith evid ence of acu te caval occlusion and su bse- w ho had chronic throm bu s fou nd at the tim e of p u l-
qu ent d ecreased card iac preload . Affected patients w ill m onary em bolectom y (251). End ovascu lar therap y for
have hyp otension and low er extremity sw elling. These p u lm onary em bolism is less effective in p atients w ho are
cases can be d istingu ished from recurrent acu te PE, as that 72 hou rs beyond the initial event and shou ld be p er-
may present w ith hyp otension bu t w ill have increased form ed only in p atients w ith a recent p u lm onary
jugu lar d istension. Cavography can confirm the d iagnosis, em bolism and a p u lm onary artery p ressu re 50 m m H g.
and throm bolytic therapy m ay be u sed to restore patency. Most initial treatm ent failu res requ ire op erative throm -
If the p atient is asym ptom atic, no intervention is requ ired , boem bolectom y, or the p atients su ccu m b to the hem od y-
as m ost clots w ill lyse spontaneously (242). nam ic com p rom ise ind u ced by the p u lm onary em bolism .
Full-thickness erosion of filter struts is seen infre- Perforation of the p u lm onary artery is a rare occu rrence
qu ently. This p roblem m ay be caused by an inflam m atory and has only been d escribed tw ice in the Greenfield series
response of the caval w all to the stru ts. Rates of strut p erfo- (250). In one instance, the com p lication w as believed to be
ration are su rp risingly high and have been reported in 30% second ary to the su ction p u lm onary em bolectom y d evice,
to 95% of filters (243). Most cases of perforation rem ain and w ith su bsequ ent m od ifications, no p erforations have
asym p tom atic, bu t erosion into surrou nd ing stru ctures has been d escribed .
been d escribed (246). These stru ctu res have includ ed the
d u od enu m and aorta and have resu lted in ulceration, hem - Mortality
orrhage, arteriovenou s fistu la, and heart failu re. These seri- Mortality rates m irror treatm ent failu re rates and range
ou s comp lications requ ire su rgical intervention. from 5% to 28%. Initial p roblem s w ith card iac arrest w ere
attribu ted to large volu m e contrast bolu s injections into
■ Venous angioplasty and stenting the m ain p u lm onary artery (250). Most short-term d eaths
are second ary to card iovascu lar collap se second ary to irre-
Technical com plications d u ring venous PTA and stent
versible right heart failu re (250–252). Other cau ses of d eath
placem ent are rare. In a large series of p atients treated for
inclu d e intracerebral hem orrhage, sep sis, and m u ltisystem
chronic venou s insu fficiency, no technical comp lications
organ failu re. Su rvival is d irectly attribu table to the proce-
occu rred and all lesions w ere technically su ccessfu lly
d u re’s su ccess. Short-term m ortality rates are as high as
treated (247). Forty-fou r of 304 lim bs treated , how ever,
73% in p atients w ith failu re of throm bu s resolution bu t
requ ired reintervention in the follow -u p p eriod d u e to
d ecrease to 17% w ith su ccessfu l treatm ent (250).
sym ptom atic restenosis. Primary patency of these stents at
24 m onths w as 71%, w ith an assisted patency rate of 97%.
Recurrent Thromboembolism
N o d eaths w ere associated w ith this proced u re, nor w ere
any d eaths evid ent in the follow -u p period . Patency rates The incid ence of recu rrent d eep venou s throm bosis (4%)
are low er in those venou s segm ents that requ ired recanal- and recurrent pulmonary embolism (4%) has been d escribed
ization d u e to com p lete occlu sion (248). Patients treated for in only one stu d y (250). These ep isod es occu rred prior to
the May—Thu rner synd rom e have sim ilarly negligible the d evelopm ent of percu taneou s placed vena cava filters.
com plication rates and com parable patency rates (249). The episod es of recurrent pulm onary em bolism presented
Com p lications associated w ith stenting of the su perior in the interval betw een p u lm onary em bolectom y and su b-
vena cava in the su p erior vena cava synd rom e have been sequ ent vena cava clip p lacem ent—w hich w as p erform ed
d escribed in case reports and in one instance w as associ- in the op erating room as a sep arate p roced u re. The place-
ated w ith card iac tam ponad e. m ent of a vena cava filter at the tim e of p u lm onary
em bolectom y, as w ell as the u se of hep arin anticoagu lation,
is beneficial in p reventing the risk of recu rrent p u lm onary
■ Endovascular therapy for pulmonary embolism em bolism .
Technical Failure
The m ost com m on com p lication in end ovascu lar treat-
m ent of p u lm onary em bolism is failu re to resolve the
■ CONCLUSIONS
throm boem bolu s. Technical failu res occu r in 5% to 39% of End ovascu lar therap ies are becom ing m ore p revalent.
cases. Most rep orts ind icate that the su ccess of end ovascu - Many of the com p lications that occu r are sim ilar am ong
lar therap y is d irectly related to the age of the p u lm onary the d ifferent interventions. An u nd erstand ing of the
em bolism . Greenfield et al. noted that em bolectom y su c- p otential ad verse events is help fu l to the su rgeon w ho is
cess w as highest for m ajor p u lm onary em bolism and m as- either requ esting the intervention or p erform ing it. Most
sive acu te p u lm onary em bolism (100% and 82% su ccess, of the com p lications can be m anaged in a noninvasive
resp ectively) and w orst for chronic p u lm onary em bolism fashion, bu t w hen they cannot be, conventional su rgery is
(56% su ccess) (250). In m ost series, failed p roced u res requ ired .
■ REFERENCES 29. Franco C, Goldsmith J, Veith F, et al. Management of arterial injuries pro-
duced by percutaneous femoral procedures. Surgery 1993;113:419–425.
1. H ou S, Bu shinksy D, Wish J, et al. H osp ital-acqu ired renal insu ffi- 30. Cragg A, N akagaw a N , Sm ith T, et al. H em atom a form ation after
ciency: a prospective stu d y. Am J Med 1983;74:243–248. d iagnostic angiography: effect of catheter size. J Vasc Interv Radiol 1991;
2. Mu rphy S, Barrett B, Parfrey P. Contrast nep hrop athy. J Am Soc 2:231–233.
Nephrol 2000;11:177–182. 31. Chitw ood R, Shep ard A, Shetty P, et al. Su rgical com p lications of
3. Berg K. N ephrotoxicity related to contrast m ed ia. Scand J Urol Nephrol transaxillary arteriograp hy: a case-control stu d y. J Vasc Surg 1996;23:
2000;34:317–322. 844–850.
4. Solom on R. N ep hrology foru m : contrast-m ed iu m -ind u ced acute 32. Kresow ick T, Khou ry M, Miller B, et al. A p rosp ective stu d y of the
renal failu re. Kidney Int 1998;53:230–242. incid ence and natu ral history of fem oral vascular com plications after
5. Barrett B. Contrast nep hrop athy. J Am Soc Nephrol 1994;5:125–137. percu taneou s translum inal coronary angiop lasty. J Vasc Surg 1991;13:
6. Katzberg R. Urograp hy in the 21st centu ry: new contrast m ed ia, renal 328–336.
hand ling, im aging characteristics, and nep hrotoxicity. Radiology 1997; 33. Dow ling K, Tod d D, Siskin G, et al. Early am bu lation after d iagnostic
204:297–312. angiograp hy using 4-F catheters and sheaths: a feasibility stu d y.
7. Liss P, N ygren A, Olsson U, et al. Effect of contrast m ed ia and m anni- J Endovasc Ther 2002;9:618–621.
tol on renal m ed u llary blood flow and red cell aggregation in the rat 34. Lönn L, Olm arker A, Gertru d K, et al. Treatm ent of fem oral p seu d oa-
kid ney. Kidney Int 1996;49:1268–1275. neu rysm . Percu taneou s US-gu id ed throm bin injection versu s US-
8. Berg K, Jakobsen J. N ep hrotoxicity related to x-ray contrast m ed ia. gu id ed com p ression. Acta Radiol 2002;43:396–400.
Adv X-ray Contrast 1993;1:10–18. 35. Spies J, Berlin L. Com p lications of fem oral artery p u nctu re. AJR Am J
9. Rud nick M, Berns J, Cohen R, et al. Contrast m ed ia-associated Roentgenol 1998;170:9–11.
nephrotoxicity. Semin Nephrol 1997;17:15–26. 36. Lilly M, Reichm an W, Srazen A, et al. Anatom ic and clinical factors
10. Cantley L, Spokes K, Clark B, et al. Role of endothelin and prostaglandins associated w ith com p lications of transfem oral arteriograp hy. Ann
in rad iocontrast-ind u ced renal artery constriction. Kidney Int 1993;44: Vasc Surg 1990;4:264–269.
1217–1223. 37. Altin R, Flicker S, N aid ech H . Pseu d oaneu rysm and arteriovenou s fis-
11. Bakris G, Burnett J. A role for calciu m in rad iocontrast-ind uced red uc- tu la after fem oral catheterization: association w ith low fem oral p u nc-
tion in renal hem od ynam ics. Kidney Int 1985;27:465–468. tu res. Am J Radiol 1989;152:629–631.
12. Bakris G, Lass N , Osam a Gaber A, et al. Rad iocontrast m ed iu m - 38. Rapop ort S, Snid erm an K, Morse S, et al. Pseu d oaneu rysm : a com p li-
ind u ced d ecline in renal fu nction: a role for oxygen free rad icals. Am J cation of fau lty techniqu e in fem oral arterial p u nctu re. Radiology 1985;
Physiol 1990;258:F115–F120. 154:529–530.
13. Katholi R, Taylor G, McCann W, et al. N ep hrotoxicity from contrast 39. Toursarkissian B, Allen B, Petrinec D, et al. Sp ontaneou s closu re of
m ed ia: attenuation w ith theop hylline. Radiology 1995;195:17–22. selected iatrogenic p seu d oaneu rysm s and arteriovenou s fistu lae.
14. Rich M, Creceliu s C. Incid ence, risk factors, and clinical cou rse of J Vasc Surg 1997;25:803–809.
acute renal insufficiency after card iac catheterization in p atients 70 40. Cox G, You ng J, Gray B, et al. Ultrasou nd -gu id ed com p ression of
years of age or old er. Arch Intern Med 1995;150:1237–1242. postcatheterization p seud oaneu rysm s: resu lts of treatm ent in one
15. Porter G. Contrast-associated nep hrop athy. Am J Cardiol 1989;64: hu nd red cases. J Vasc Surg 1994;19:683–686.
22E–26E. 41. Elford J, Bu rrell C, Freem an S, et al. H u m an throm bin injection for the
16. Levy E, Viscoli C, H orw itz R. The effect of acu te renal failu re on m or- percu taneou s treatm ent of iatrogenic p seu d oaneu rysm s. Cardiovasc
tality: a cohort analysis. J Am Med Assoc 1996;275:1489–1494. Intervent Radiol 2002;25:115–118.
17. Ru d nick M, Gold farb S, Wexler L, et al. N ep hrotoxicity of ionic and 42. Waigand J, Uhlich F, Gross M, et al. Percu taneou s treatm ent of
nonionic contrast m ed ia in 1196 p atients: a rand om ized trial. Kidney pseud oaneu rysm and arteriovenou s fistulas after invasive vascular
Int 1995;47:254–261. proced u res. Catheter Cardiovasc Interv 1999;47:157–164.
18. Mu eller C, Bu erkle G, Bu ettner H . Prevention of contrast m ed ia-asso- 43. Thalham m er C, Kirchherr A, Uhlich F, et al. Postcatheterization
ciated nephropathy: rand om ized com p arison of 2 hyd ration regim ens pseu doaneurysm and arteriovenous fistulas: repair w ith percutaneous
in 1620 patients u nd ergoing coronary angiograp hy. Arch Intern Med im plantation of end ovascular covered stents. Radiology 2000;214:
2002;162:329–336. 127–131.
19. Weisberg L, Kurnik P, Kurnik B. Dopamine and renal blood flow in 44. Kent K, Mosu cci M, Gallagher S, et al. N eu rop athy after card iac
rad iocontrast-ind uced nephropathy in humans. Ren Fail 1993;15:61–68. catheterization: incid ence, clinical p atterns, and long-term ou tcom e. J
20. Abizaid A, Clark C, Mintz G, et al. Effects of d op am ine and am ino- Vasc Surg 1994;19:1008–1014.
phylline on contrast-ind u ced acu te renal failu re after coronary angio- 45. Mills J, Wied em an J, Robison J, et al. Minim izing m ortality and m or-
plasty in patients w ith p reexisting renal insu fficiency. Am J Cardiol bid ity from iatrogenic arterial inju ries: the need for early recognition
1999;83:260–263. and p rom pt rep air. J Vasc Surg 1986;4:22–27.
21. Tu m lin J, Finkel K, Mu rray P, et al. Fenold op am m esylate in early 46. Tron C, Koning R, Eltchaninoff H , et al. A rand om ized com p arison of
acute tubular necrosis: a rand om ized , d ou ble-blind , p lacebo-con- a p ercu taneou s su tu re d evice versu s m anu al com pression for fem oral
trolled clinical trial. Am J Kidney Dis 2005;46:26–34. artery hem ostasis after PTCA. J Intervent Cardiol 2003;16:217–221.
22. Birck R, Krzossok S, Markow etz F, et al. Acetylcysteine for p revention 47. Sanborn T, Gibbs H , Brinker J, et al. A m u lticenter rand om ized trial
of contrast nep hrop athy: m eta-analysis. Lancet 2003;362:598–603. com paring a p ercutaneous collagen hem ostasis d evice w ith conven-
23. Brigu ori C, Airold i F, D’And rea D, et al. Renal insu fficiency follow ing tional m anu al com p ression after d iagnostic angiograp hy and angio-
contrast med ia ad m inistration trial (REMEDIAL). Circulation 2007;115: plasty. J Am Coll Cardiol 1993;22:1273–1279.
1211–1217. 48. Wetter D, Rickli H , von Sm ekal A, et al. Early sheath rem oval after
24. Koch J, Plu m J, Grabensee B, et al. Prostagland in E1: a new agent for coronary artery interventions w ith use of a suture-m ed iated closure
the p revention of renal d ysfunction in high risk patients cau sed by d evice: clinical outcom e and resu lts of Dop p ler US evalu ation. J Vasc
rad iocontrast m ed ia? Nephrol Diol Transplant 2000;15:43–49. Interv Radiol 2000;11:1033–1037.
25. Sp argias K, Ad reanid es E, Glam ou zis G, et al. Ilop rost for p revention 49. Michalis L, Rees M, Patsou ras D, et al. A p rosp ective rand om ized trial
of contrast-m ed iated nep hrop athy in high-risk p atients u nd ergoing a com paring the safety and efficacy of three com m ercially available clo-
coronary proced u re. Resu lts of a rand om ized p ilot stu d y. Eur J Clin su re d evices (Angioseal, Vasoseal and Du ett). Cardiovasc Intervent
Pharmacol 2006;62:589–595. Radiol 2002;25:423–429.
26. Messina L, Brothers T, Wakefield T, et al. Clinical characteristics and 50. Korn ow ski R, Brand es S, Tep litsky I, et al. Safety an d efficacy of a 6
su rgical m anagem ent of vascu lar com p lications in p atients u nd ergo- French p erclose arterial su tu ring d evice follow ing p ercu taneou s
ing card iac catheterization: interventional versus d iagnostic p roce- coron ary interven tions: a p ilot evalu ation. J Invasive Cardiol 2002;14:
d u res. J Vasc Surg 1991;13:593–600. 741–745.
27. Mu ller D, Pod d J, Sham ir K, et al. Vascu lar access site com plications in 51. Sesana M, Vaghetti M, Albiero R, et al. Effectiveness and com p lica-
the era of com plex p ercu taneou s coronary interventions. Circulation tions of vascu lar access closu re d evices after interventional p roce-
1990;82:510. d u res. J Invasive Cardiol 2000;12:395–399.
28. You ng N , Chi K-K, Ajaka J, et al. Com p lications w ith ou tp atient 52. Meyerson S, Feld m an T, Desai T, et al. Angiograp hic access site com -
angiography and interventional proced ures. Cardiovasc Intervent Radiol plications in the era of arterial closu re d evices. Vasc Endovasc Ther
2002;25:123–126. 2002;36:137–144.
53. Starnes B, O’Donnell S, Gillesp ie D, et al. Percu taneou s arterial clo- 80. Malek A, H igashid a R, Phatou ros C, et al. Stent angiop lasty for cervi-
sure in peripheral vascu lar d isease: a prospective rand om ized evalua- cal carotid artery stenosis in high-risk sym ptom atic N ASCET-ineligi-
tion of the Perclose d evice. J Vasc Surg 2003;38:263–271. ble p atients. Stroke 2000;31:3029–3033.
54. Dangas G, Mehran R, Kokolis S, et al. Vascu lar com p lications after 81. Ross C, N aslu nd T, Ranval T. Carotid stent-assisted angiop lasty: the
p ercu taneou s coronary interventions follow ing hem ostasis w ith m an- new est ad d ition to the surgeons’ arm am entarium in the m anagem ent
u al com pression versu s arteriotom y closu re d evices. J Am Coll Cardiol of carotid occlu sive d isease. Am Surg 2002;68:967–975.
2001;38:638–641. 82. N ew G, Iyer S, Dietrich E, et al. Safety, efficacy, and d u rability of
55. Arora N , Matheny M, Sep ke C, et al. A p rop ensity analysis of the risk carotid artery stenting for restenosis follow ing carotid end arterec-
of vascular com plications after card iac catheterization p roced u res tom y: a m ulticenter stu d y. J Endovasc Ther 2000;7:345–352.
w ith the use of vascular closu re d evices. Am Heart J 2007;153:606–611. 83. H obson RI, Lal B, Chaktou ra E, et al. Carotid artery stenting: analysis
56. Goyen M, Manz S, Kroger K, et al. Interventional therap y of vascu lar of d ata for 105 p atients at high risk. J Vasc Surg 2003;37:1234–1239.
com plications caused by the hem ostatic p u nctu re closu re d evice 84. H ow ell M, Krajcer Z, Dou gherty K, et al. Correlation of p erip roce-
angio-seal. Catheter Cardiovasc Interv 2000;49:142–147. d u ral systolic blood p ressu re changes w ith neu rologic events in high-
57. Carere R, Webb J, Miyagishim a R, et al. Groin com p lications associ- risk carotid stent p atients. J Endovasc Ther 2002;9:810–816.
ated w ith collagen p lu g closu re of fem oral arterial p u nctu re sites in 85. Schw arten D. Extracranial brachiocep halic angiop lasty. In: Bau m S,
anticoagu lated p atients. Catheter Cardiovasc Diag 1998;43:124–129. Pentecost M, ed s. Abram’s angiography: interventional radiology. Boston,
58. H offer E, Bloch R. Percu taneou s arterial closu re d evice. J Vasc Interv MA: Brow n and Com p any; 1997:339–355.
Radiol 2003;14:865–885. 86. Castriota F, Crem onesi A, Manetti R, et al. Im p act of cerebral p rotec-
59. Good ney P, Chang R, Cronenw ett J. A p ercutaneou s arterial closu re tion d evices on early outcom e of carotid stenting. J Endovasc Ther
p rotocol can d ecrease com p lications after end ovascu lar interventions 2002;9:786–792.
in vascular surgery patients. J Vasc Surg 2008;48:1481–1488. 87. Wilentz J, Chati Z, Krafft V, et al. Retinal em bolization d u ring carotid
60. Egglin T, O’Moore P, Feinstein A, et al. Com p lications of p eripheral angiop lasty and stenting: m echanism s and role of cerebral p rotection
angiograp hy: a new system to id entify p atients at increased risk. J system s. Catheter Cardiovasc Diagn 2002;56:320–327.
Vasc Surg 1995;22:787–794. 88. Macd onald S, McKevitt F, Venables G, et al. N eu rologic ou tcom es
61. Daw son P, Strickland N . Throm boem bolic p henom ena in clinical after carotid stenting p rotected w ith N euroShield filter com pared to
angiography: a role of m aterials and techniqu es. J Vasc Interv Radiol u np rotected stenting. J Endovasc Ther 2002;9:777–785.
1991;2:125. 89. Martin J-B, Pache J-C, Treggiari-Venzi M, et al. Role of the d istal bal-
62. Form anek G, Frech R, Am p latz K. Arterial throm bu s form ation d ur- loon protection techniqu e in the p revention of cerebral em bolic event
ing clinical percu taneou s catheterization. Circulation 1970;41:833–839. d u ring carotid stent placem ent. Stroke 2001;32:479–484.
63. van And el G. Arterial occlu sion follow ing angiograp hy. Br J Radiol 90. Rapp J, Wakil L, Saw hney R, et al. Su bclinical em bolization after
1980;53:747–753. carotid artery stenting: new lesions on d iffu sion-w eighted m agnetic
64. Bolasny B, Killen D. Su rgical m anagem ent of arterial inju ries second - resonance im aging occu r p ostp roced u re. J Vasc Surg 2007;45:867–872.
ary to angiography. Ann Surg 1971;174:962–964. 91. Crem onesi A, Manetti R, Setacci F, et al. Protected carotid stenting:
65. Fine M, Kapoor W, Falanga V. Cholesterol crystal em bolization: a clinical ad vantages and com plications of em bolic protection d evices
review of 221 cases in the English literatu re. Angiology 1987;38: in 442 consecu tive p atients. Stroke 2003;34:1936–1943.
769–784. 92. Chaer R, Trocciola S, DeRu bertis B, et al. Cerebral ischem ia associated
66. Descham ps P, Leroy D, Mand ard J, et al. Cholesterol em bolism in the w ith Percu Su rge balloon occlu sion balloon d u ring carotid stenting:
low er lim bs. Br J Dermatol 1977;97:93–97. incid ence and p ossible m echanism s. J Vasc Surg 2006;43:946–952.
67. H end ricks I, Monti M, Manasse E, et al. Severe cu taneou s cholesterol 93. Parod i J, Ferreira LM, Sicard G, et al. Cerebral p rotection d u ring
em boli synd rom e after coronary angiograp hy. Eur J Cardiothorac Surg carotid stenting u sing flow reversal. J Vasc Surg 2005;41:416–422.
1999;15:215–217. 94. Eskand ari M. Preventable com p lications of carotid stenting. Perspect
68. Dion J, Gates P, Fox A, et al. Clinical events follow ing neu roangiogra- Vasc Surg Endovasc Ther 2008;20(1):17–25.
p hy: a p rospective stu d y. Stroke 1987;18:997–1004. 95. Ohki T, Veith F, Grenell S, et al. Initial exp erience w ith cerebral p rotec-
69. H ankey G, Warlow C, Sellar R. Cerebral angiograp hic risk in m ild tion d evices to p revent em bolization d u ring carotid stenting. J Vasc
cerebrovascular d isease. Stroke 1990;21(2):209–222. Surg 2002;36:1175–1185.
70. Davies K, H u m phrey P. Com p lications of cerebral angiograp hy in 96. H obson RI, H ow ard V, Rou bin G, et al. Carotid artery stenting is asso-
p atients w ith sym p tom atic carotid territory ischem ia screened by ciated w ith increased com p lications in octogenarians: 30 d ay stroke
carotid u ltrasou nd . J Neurol Neurosurg Psychiatry 1993;56:967–972. and d eath rates in the CREST lead in p hase. J Vasc Surg
71. Johnston D, Chapm an K, Gold stein L. Low rate of com p lications of 2004;40:1106–1111.
cerebral angiograp hy in rou tine clinical p ractice. Neurology 2001;57: 97. Dangas G, Laird JR, Satler LF, et al. Postp roced u ral hyp otension after
2012–2014. carotid artery stent placem ent: pred ictors and short- and long-term
72. Theod otou B, Whaley R, Mahaley M. Com p lications follow ing trans- clinical ou tcom es. Radiology 2000;190:691–695.
fem oral cerebral angiograp hy for cerebral ischem ia: rep ort of 159 98. Qu reshi AI, Lu ft AR, Sharm a M. Frequ ency and d eterm inants of p ost-
angiogram s and correlation w ith su rgical risk. Surg Neurol 1987;28: p roced u ral hem od ynam ic instability after carotid angiop lasty and
90–92. stenting. Stroke 1999;30:2086–2093.
73. Marku s H , Loh A, Israel D, et al. Microscopic air em bolism d u ring 99. Yad av J, Rou bin G, Iyer S, et al. Elective stenting of the extracranial
cerebral angiography and strategies for its avoid ance. Lancet 1993;341: carotid arteries. Circulation 1997;95:376–381.
784–787. 100. Bergeron P, Becqu em in J-P, Jau sseran J-M, et al. Percu taneou s stenting
74. Woolfend en A, O’Brien M, Schw artzberg R, et al. Diffu sion-w eighted of the internal carotid artery: the Eu rop ean CAST-1 stu d y. J Endovasc
MRI in transient global am nesia precipitated by cerebral angiography. Surg 1999;6:155–159.
Stroke 1997;28:2311–2314. 101. H enry M, Am or M, Masson I, et al. Angiop lasty and stenting of the
75. Bend szus M, Koltzenbu rg M, Bu rger R, et al. Silent em bolization in extracranial carotid arteries. J Endovasc Surg 1998;5:293–304.
d iagnostic cerebral angiograp hy and neu rointerventional p roced u res: 102. Al-Mu barak N , Rou bin G, Gom ez C, et al. Carotid artery stenting in
a prospective stud y. Lancet 1999;354:1594–1597. p atients w ith high neu rologic risks. Am J Cardiol 1999;83:1411–1413.
76. Wholey MH , Wholey M, Bergeron P, et al. Cu rrent global statu s of 103. Willfort-Ehringer A, Ahm ad i R, Gschw ad tner M, et al. Single-center
carotid stent placem ent. Catheter Cardiovasc Diag 1998;44:1–6. exp erience w ith carotid stent restenosis. J Endovasc Ther
77. Mas JL, Chatellier GB, Beyssen B, et al. End arterectom y versu s stent- 2002;9:299–307.
ing in p atients w ith sym p tom atic severe carotid stenosis. N Engl J Med 104. Lal B, H obson RI, Gold stein J, et al. In-stent recu rrent stenosis after
2006;355:1660–1671. carotid artery stenting: life table analysis and clinical relevance. J Vasc
78. Faggioli G, Ferri M, Freyrie A, et al. Aortic arch anom alies are associ- Surg 2003;38:1162–1169.
ated w ith increased risk of neu rological events in carotid stent p roce- 105. Becker G, Palm az J, Rees C, et al. Angiop lasty-ind u ced d issections in
d u res. Eur J Vasc Endovasc Surg 2007;33:436–441. hum an iliac arteries: m anagem ent w ith Palm az balloon-expand able
79. Roubin G, Yad av S, Vitek J. Carotid stent-su p p orted angiop lasty: a intralu m inal stents. Radiology 1990;176:31–38.
neu rovascu lar intervention to p revent stroke. Am J Cardiol 1998;78: 106. Bend ok B, Rou bin G, Katzen B, et al. Cu tting balloon to treat carotid
8–12. in-stent stenosis: technical note. J Invasive Cardiol 2003;15:227–232.
107. Rod rigu ez-Lopez J, Werner A, Martinez R, et al. Stenting for athero- 137. Schillinger M, Exner M, Mleku sch W, et al. Fibrinogen p red icts
sclerotic occlu sive d isease of the su bclavian artery. Ann Vasc Surg restenosis after end ovascu lar treatm ent of the iliac arteries. Thromb
1999;13:254–260. Haemost 2002;87:959–965.
108. Ringelstein E, Zeu m er H . Delayed reversal of vertebral artery blood 138. Mu rphy K, Encarnacion C, Le V, et al. Iliac artery stent p lacem ent
flow follow ing p ercu taneou s translu m inal angiop lasty for su bclavian w ith the Palm az stent: follow -u p stu d y. J Vasc Interv Radiol 1995;6:
steal synd rom e. Neuroradiology 1984;26:189–198. 321–329.
109. Su llivan T, Gray B, Bacharach J, et al. Angiop lasty and p rim ary stent- 139. Zarins C, White R, Schw arten D, et al. Aneu Rx stent graft versu s op en
ing of the subclavian, innom inate, and com m on carotid arteries in 83 su rgical rep air of abd om inal aortic aneu rysm s: m u lticenter p rosp ec-
p atients. J Vasc Surg 1998;28:1059–1065. tive clinical trial. J Vasc Surg 1999;29:292–305.
110. Queral L, Criad o F. The treatm ent of focal aortic arch branch lesions 140. May J, White G, Wau gh R, et al. Im p roved su rvival after end olu m inal
w ith Palm az stents. J Vasc Surg 1996;23:368–375. rep air w ith second -generation p rostheses com p ared w ith op en rep air
111. Al-Mu barak N , Liu M, Dean L, et al. Im m ed iate and late ou tcom es of in the treatm ent of abd om inal aortic aneu rysm s: a 5-year concu rrent
su bclavian artery stenting. Catheter Cardiovasc Interv 1999;46:169–172. com p arison using life table m ethod . J Vasc Surg 2001;33:S21–S26.
112. Lin P, Bu sh R, Weiss V, et al. Su bclavian artery d isru p tion resu lting 141. Lee W, O’Dorisio J, Wolf Y, et al. Ou tcom e after u nilateral hyp ogastric
from end ovascular intervention: treatm ent op tions. J Vasc Surg 2000; artery occlu sion d uring end ovascu lar aneu rysm rep air. J Vasc Surg
32:607–611. 2001;33:921–926.
113. Xenos E, Freem an M, Stevens S, et al. Covered stents for injuries of 142. Wolp ert L, Dittrich K, H allisey M, et al. H yp ogastric artery em boliza-
su bclavian and axillary arteries. J Vasc Surg 2003;38:451–454. tion in end ovascu lar abd om inal aortic aneu rysm rep air. J Vasc Surg
114. Malek A, H igashid a R, Reilly L, et al. Su bclavian arteritis and 2001;33:1193–1198.
p seu d oaneurysm form ation second ary to stent infection. Cardiovasc 143. Criad o F, Wilson E, Velazqu ez O, et al. Safety of coil em bolization of
Intervent Radiol 2000;23:57–60. the internal iliac artery in end ovascular grafting of abd om inal aortic
115. H ad jipetrou P, Cox S, Piem onte T, et al. Percu taneou s revascu lariza- aneu rysm s. J Vasc Surg 2000;32:684–688.
tion of atherosclerotic obstru ction of aortic arch vessels. J Am Coll Car- 144. Schod er M, Zau nbauer L, H olzenbein T, et al. Internal iliac artery
diol 1999;33:1238–1245. em bolization before end ovascu lar repair of abd om inal aortic
116. Schillinger M, H au m er M, Schillenger S, et al. Risk stratification for aneurysms: frequency, efficacy, and clinical results. Am J Radiol 2001;177:
su bclavian artery angiop lasty: is there an increased rate of restenosis 599–605.
after stent im plantation? J Endovasc Ther 2001;8:550–557. 145. Mehta M, Veith F, Ohki T, et al. Unilateral and bilateral hyp ogastric
117. Korner M, Bau m gartner I, Do D, et al. PTA of the su bclavian and artery interru p tion d u ring aortoiliac aneu rysm rep air in 154 p atients:
innom inate arteries: long-term resu lts. Vasa 1999;28:117–122. a relatively innocu ou s p roced u re. J Vasc Surg 2001;33:S27–S32.
118. Tegtm eyer C, H artw ell G, Selby J, et al. Resu lts and com p lications of 146. Kritp racha B, Pigott J, Price C, et al. Distal internal iliac artery
angioplasty in aortoiliac d isease. Circulation 1991;83:I53–I60. em bolization: a p roced u re to avoid . J Vasc Surg 2003;37:943–948.
119. Belli A, Cu m berland D, Knox A, et al. Resu lts and com plications of 147. Wyers M, Sherm erhorn M, Fillinger M, et al. Internal iliac occlu sion
angioplasty in aortoiliac d isease. Clin Radiol 1990;41:380–383. w ithou t coil em bolization d uring end ovascular abd om inal aortic
120. Al-H am ali S, Baskerville P, Fraser S, et al. Detection of d istal em boli in aneu rysm repair. J Vasc Surg 2002;36:1138–1145.
p atients w ith perip heral arterial stenosis before and after iliac angio- 148. White G, Yu W, May J. End oleak: a p rop osed new term inology to
p lasty: a prospective stu d y. J Vasc Surg 1999;29:345–351. d escribe incom p lete aneu rysm exclu sion by an end olu m inal graft. J
121. Gard iner GA Jr, Meyerovitz M, Stokes K, et al. Com p lications of trans- Endovasc Surg 1996;3:124–125.
lum inal angiop lasty. Radiology 1986;159:201–208. 149. White G, May J, Wau gh R, et al. Typ e I and typ e II end oleaks: a m ore
122. Ballard J, Sparks S, Taylor F, et al. Com p lications of iliac artery stent u sefu l classification for rep orting resu lts of end olu m inal AAA rep air. J
d eploym ent. J Vasc Surg 1996;24:545–555. Endovasc Surg 1998;5:189–191.
123. Palm az J, Labord e J, Rivera F, et al. Stenting of the iliac arteries w ith 150. White G, May J, Waugh R, et al. Typ e III and typ e IV end oleaks:
the Palm az stent: exp erience from a m u lticenter trial. Cardiovasc Inter- tow ard a com plete d efinition of blood flow in the sac after end olu m i-
vent Radiol 1992;15:291–297. nal AAA rep air. J Endovasc Surg 1998;5:305–309.
124. Allaire E, Melliere D, Pou ssier B, et al. Iliac artery ru p tu re d u ring bal- 151. Ou riel K, Greenberg R, Clair D. End ovascu lar treatm ent of aortic
loon d ilatation: w hat treatm ent? Ann Vasc Surg 2003;17:306–314. aneu rysm . Curr Probl Surg 2002;39:233.
125. Trost D, Jagu st M, Weiss M, et al. Percu taneou s p u nctu re of nond eflat- 152. Zarins C, White R, H od gson K, et al. End oleak as a p red ictor of ou t-
ing angioplasty balloons. J Vasc Interv Radiol 1999;10:924–926. com e after end ovascular aneu rysm rep air: Aneu Rx m u lticenter clini-
126. Parham W, Puri S, Bitar S, et al. Management of iliac stent movement cal trial. J Vasc Su rg 2000;32:90–107.
complicating peripheral vascular intervention: a rescue technique when 153. H olzenbein T, Kretschm er G, Thu rnher S, et al. Mid term d u rability of
stent d eployment malfunctions. J Invasive Cardiol 2003;15:277–279. abd om inal aortic aneu rysm end ograft rep air: a w ord of cau tion. J Vasc
127. Bu nt T, Gill H , Sm ith D, et al. Infection of a chronically im p lanted iliac Surg 2001;33:S46–S54.
artery stent. Ann Vasc Surg 1997;11:529–532. 154. Buth J, H arris P, van Marrew ijk C, et al. The significance and m anage-
128. Deip arine M, Ballard J, Taylor F, et al. End ovascu lar stent infection. J m ent of d ifferent types of end oleaks. Semin Vasc Surg 2003;16:95–102.
Vasc Surg 1996;23:529–533. 155. Chu ter T, Faru qi R, Saw hney R, et al. End oleak after end ovascu lar
129. Therasse E, Sou lez G, Cartier P, et al. Infection w ith fatal ou tcom e rep air of abd om inal aortic aneu rysm . J Vasc Surg 2001;34:98–105.
after end ovascu lar m etallic stent. Radiology 1994;192:363–365. 156. Buth J, Laheji R. Early com p lications and end oleaks after end ovascu -
130. Palm az J. Intravascu lar stents: tissu e—stent interaction and d esign lar abd om inal aortic aneu rysm rep air: rep ort of a m u lticenter stu d y. J
consid eration. Am J Roentgenol 1993;160:613–618. Vasc Surg 2000;31:134–146.
131. Johnston K, Rae M, H ogg-Johnston S, et al. 5-Year resu lts of a p rosp ec- 157. Dattilo J, Brew ster D, Fan C-M, et al. Clinical failu res of end ovascu lar
tive stud y of percutaneous transluminal angioplasty. Ann Surg 1987;206: abd om inal aortic aneurysm rep air: incid ence, cau ses, and m anage-
403–413. m ent. J Vasc Surg 2002;35:1137–1144.
132. Yasu hara H , Shigem atsu H , Mu to T. Risk factors for restenosis after 158. Zarins C. The US Aneu Rx clinical trial: 6-year clinical u p d ate. J Vasc
balloon angioplasty in focal iliac stenosis. Surgery 1998;123:658–665. Surg 2002;37:904–908.
133. Bosch J, H u nink M. Meta-analysis of the resu lts of p ercu taneou s 159. Fairm an R, Carpenter J, Bau m R, et al. Potential im p act of therap eu tic
translu m inal angiop lasty and stent p lacem ent for aortoiliac occlu sive w arfarin treatm ent on type II end oleaks and sac shrinkage rates on
d isease. Radiology 1997;204:87–96. m id term follow -up exam ination. J Vasc Surg 2002;35:679–685.
134. Leville C, Kashyap V, Clair D, et al. End ovascu lar m anagem ent of iliac 160. Bau m R, Carp enter J, Cop e C, et al. Aneu rysm sac p ressu re m easu re-
artery occlu sions: extend ing treatm ent to TransAtlantic Inter-Society m ents after end ovascu lar rep air of abd om inal aortic aneu rysm s.
Consensus class C and D p atients. J Vasc Surg 2006;43:32–39. J Vasc Surg 2001;33:32–41.
135. Tim aran C, Stevens S, Freem an M, et al. Pred ictors for ad verse out- 161. Jacobs T, Teod orescu V, Morrissey N , et al. The end ovascu lar rep air of
com e after iliac angioplasty and stenting for lim b-threatening abd om inal aortic aneu rysm : an u pd ate analysis of stru ctu ral failu re
ischem ia. J Vasc Surg 2002;36:507–513. m od es of end ovascu lar grafts. Semin Vasc Surg 2003;16:103–112.
136. Vorw erk D, Gu enth er R, Schu rm an n K, et al. Late reobstru ction in 162. Stelter W, Um scheid T, Ziegler P. Three-year exp erience w ith m od u lar
iliac arterial sten ts: p ercu taneou s treatm ent. Radiology 1995;197: stent-graft d evices for end ovascu lar AAA treatm ent. J Endovasc Surg
479–483. 1997;4:362–369.
163. Beebe H , Cronenw ett J, Katzen B, et al. Resu lts of an aortic end ograft 187. Lee J, Lee J, Aziz I, et al. Stent-graft m igration follow ing end ovascu lar
trial: im pact of d evice failu re beyond 12 m onths. J Vasc Surg 2001;33: repair of aneurysm s w ith large p roxim al necks: anatom ical risk fac-
S55–S63. tors and long-term sequ elae. J Endovasc Ther 2002;9:652–664.
164. Alim i Y, Chakfe N , Rivoal E, et al. Ru p tu re of an abd om inal aortic 188. N aslu nd T, Ed w ard s W, N eu zil D, et al. Technical com p lications of
aneu rysm after end ovascu lar graft p lacem ent and aneu rysm size end ovascular abd om inal aortic aneu rysm rep air. J Vasc Surg 1997;26:
red u ction. J Vasc Surg 1998;28:178–183. 502–510.
165. Riep e G, H eilberger P, Um schield T, et al. Fram e d islocation of bod y 189. Fairm an R, Velazqu ez O, Bau m R, et al. End ovascu lar rep air of aortic
m id d le rings in end ovascu lar stent tu be grafts. J Endovasc Surg 1999; aneu rysm s: critical events and ad ju nctive p roced u res. J Vasc Surg
17:28–34. 2001;33:1226–1232.
166. Jacobs T, Won J, Graverau x E, et al. Mechanical failu re of p rosthetic 190. Moore W, Matsu m ura J, Makarou n M, et al. Five-year interim com -
hu m an im p lants: a 10-year exp erience w ith aortic stent graft d evices. p arison of the Gu id ant bifurcated end ograft w ith open rep air of
J Vasc Surg 2003;37:16–26. abd om inal aortic aneu rysm . J Vasc Surg 2003;38:46–55.
167. H eintz C, Riep e G, Birken L. Corrod ed nitinol w ires in exp lanted aor- 191. Becker G, Kovacs M, Mathison M, et al. Risk stratification and ou t-
tic end ografts: an im portant m echanism of failure? J Endovasc Ther com es of translu m inal end ografting for abd om inal aortic aneurysm :
2001;8:248–253. 7-year experience and long-term follow -u p . J Vasc Interv Radiol
168. Trepanier C, Tabrizian M, Yahia L, et al. Effect of m od ification of oxid e 2003;12:1033–1046.
layer on N iTi stent corrosion resistance. J Biomed Mater Res B Appl Bio- 192. Laheji R, Bu th J, H arris P, et al. N eed for second ary interventions
mater 1998;43:433–440. after end ovascu lar rep air of abd om inal aortic an eu rysm s. In term e-
169. Duerig T, Pelton A, Stöckel D. An overview of nitinol m ed ical ap plica- d iate-term follow -u p resu lts of a Eu rop ean collaborative registry
tions. Mater Sci Eng A Struct Mater 1999;273–275:149–160. (EUROSTAR). Br J Surg 2000;87:1666–1673.
170. Starosvetsky E, Gotm an I. Corrosion behavior of titaniu m nitrid e 193. Ou riel K, Clair D, Greenberg R, et al. End ovascu lar rep air of abd om i-
coated N i—Ti shape m em ory su rgical alloy. Biomaterials 2001;22: nal aortic aneu rysm s: d evice-sp ecific ou tcom e. J Vasc Surg 2003;37:
1853–1859. 991–998.
171. Fairm an R, Bau m R, Carp enter J, et al. Lim b interventions in patients 194. EVAR Trial Participants. End ovascu lar aneu rysm rep air versu s op en
u nd ergoing treatm ent w ith an u nsu p p orted bifu rcated aortic end o- rep air in p atients w ith abd om inal aortic aneu rysm (EVAR trial 1): ran-
graft system : a review of the p hase II EVT trial. J Vasc Surg 2002;36: d om ised controlled trial. Lancet 2005;365:2179–2186.
118–126. 195. Blankensteijn J, d e Jong S, Prinssen M, et al. Tw o-year ou tcom es after
172. Carroccio A, Faries P, Morrissey N , et al. Pred icting iliac lim b occlu - conventional or end ovascular repair of abd om inal aortic aneu rysm s.
sion after bifurcated aortic stent grafting: anatom ic and d evice-related N Engl J Med 2005;352:2398–2405.
cau ses. J Vasc Surg 2002;36:679–684. 196. Criad o F, Abu l-Khou d ou d O, Dom er G, et al. End ovascu lar rep air of
173. Baum R, Shetty S, Carp enter J, et al. Lim b kinking in su p p orted and the thoracic aorta: lessons learned . Ann Thorac Surg 2005;80:857–863.
u nsup ported abd om inal aortic stent-grafts. J Vasc Interv Radiol 2000; 197. Makaroun M, Dillavou E, Wheatley G, et al. Gore TAG Investigators:
11:1165–1171. Five-year resu lts of end ovascu lar treatm ent w ith the Gore TAG d evice
174. Am esu r N , Zajko A, Orons P, et al. End ovascu lar treatm ent of iliac com p ared w ith op en rep air of thoracic aortic aneu rysm s. J Vasc Surg
lim b stenoses or occlu sion in 31 p atients treated w ith the Ancu re 2008;47:912–918.
end ograft. J Vasc Interv Radiol 2000;11:421–428. 198. Greenberg R, Lu Q, Roselli E, et al. Contem p orary analysis of
175. Ohki T, Veith F, Shaw P, et al. Increasing incid ence of m id term and d escend ing thoracic and thoracoabd om inal aneu rysm rep air. A com -
long-term com plications after end ovascular graft repair of abd om inal p arison of end ovascu lar and op en techniqu es. Circulation 2008;118:
aortic aneurysm s: a note of cau tion based on a 9-year exp erience. Ann 808–817.
Surg 2001;234:323–335. 199. Matsu m u ra J, Cam bria R, Dake M, et al. International controlled clin-
176. Carp enter J, N eschis D, Fairm an R, et al. Failu re of end ovascular ical trial of thoracic end ovascu lar aneu rysm repair w ith the Zenith
abd om inal aortic aneu rysm graft lim bs. J Vasc Surg 2001;33:296–303. TX2 end ovascu lar graft: 1-year resu lts. J Vasc Surg 2008;47:247–257.
177. Sam pram E, Karafa M, Mascha E, et al. N atu re, frequ ency, and p red ic- 200. Fairm an R, Farber M, Kw olek C, et al. Pivotal resu lts of the Med tronic
tors of second ary p roced u res after end ovascu lar rep air of abd om inal Vascular Talent Thoracic Stent Graft System for patients w ith thoracic
aortic aneurysm . J Vasc Surg 2003;37:930–937. aortic d isease: the VALOR trial. J Vasc Surg 2008;48:546–554.
178. Cao P, Verzini F, Zannetti S, et al. Device m igration after end olu m inal 201. Morales J, Greenberg R, Morales C, et al. Thoracic aortic lesions
abd om inal aortic aneu rysm rep air: analysis of 113 cases w ith a m ini- treated w ith Zenith TX1 and TX2 thoracic d evices: interm ed iate and
m u m follow -up p eriod of 2 years. J Vasc Surg 2002;35:229–235. long-term ou tcom es. J Vasc Surg 2008;48:54–63.
179. Law rence-Brow n M, Sem m ens J, H artley D, et al. H ow is d urability 202. Chaer R, Makaroun M. Late failu re after end ovascu lar rep air of
related to p atient selection and graft d esign w ith end olu m inal graft- d escend ing thoracic aneurysm s. Sem Vasc Surg 2009;22:81–86.
ing for abd om inal aortic aneu rysm ? In: Greenlau gh R, ed . The durabil- 203. Matsu m oto A, Angle J, Sp inosa D, et al. Percu taneou s translu m inal
ity of vascular and endovascular surgery. Lond on: WB Sau nd ers; 1999: angiop lasty and stenting in the treatm ent of chronic m esenteric
375–385. ischem ia: resu lts and longterm follow u p . J Am Coll Surg 2002;194(1,
180. Resch T, Malina M, Lind blad B, et al. The im p act of stent d esign on Su pp l):S22–S31.
p roxim al stent-graft fixation in the abd om inal aorta: an exp erim ental 204. Steinmetz E, Tatou E, Favier-Blavoux C, et al. Endovascular treatment as
stu d y. Eur J Vasc Endovasc Surg 2000;20:190–195. first choice in chronic intestinal ischemia. Ann Vasc Surg 2002;16:693–699.
181. Albertini J-N , Kalliafas S, Travis S, et al. Anatom ical risk factors for 205. Sharafu d d in M, Olson C, Su n S, et al. End ovascu lar treatm ent of celiac
p roxim al p erigraft end oleak and graft m igration follow ing end ovas- and m esenteric arteries stenoses: ap p lication and resu lts. J Vasc Surg
cular rep air of abd om inal aortic aneu rysm s. Eur J Vasc Endovasc Surg 2003;38:692–698.
2000;19:308–312. 206. Kasirajan K, Dolm atch B, Ou riel K, et al. Delayed onset of ascend ing
182. Resch T, Ivancev K, Bru nkw all J, et al. Distal m igration of stent-grafts paralysis after thoracic aortic stent graft d ep loym ent. J Vasc Surg 2000;
after end ovascu lar rep air of abd om inal aortic aneu rysm s. J Vasc Interv 38:692–698.
Radiol 1997;10:257–264. 207. Sheeran S, Mu rp hy T, Khw aja A, et al. Stent p lacem ent for treatm ent
183. H arris P, Brennan J, Martin J, et al. Longitu d inal aneu rysm shrinkage of m esenteric artery stenoses or occlu sions. J Vasc Interv Radiol 1999;
follow ing end ovascular aortic aneu rysm repair: a source of interm e- 10:861–867.
d iate and late com plications. J Endovasc Surg 1999;6:11–16. 208. Ivanovic V, McKu sick M, Johnson CI, et al. Renal artery stent p lace-
184. White G, May J, Wau gh R, et al. Shortening of end ografts d u ring m ent: com plications at a single tertiary care center. J Vasc Interv Radiol
d eploym ent in end ovascu lar AAA rep air. J Endovasc Ther 1999;6:4–10. 2003;14:217–225.
185. Prinssen M, Wever J, Mali W, et al. Concerns for the d u rability of the 209. Bu sh R, N ajibi S, MacDonald J, et al. End ovascu lar revascu larization
p roxim al abd om inal aortic aneu rysm end ograft fixation from a 2-year of renal artery stenosis: technical and clinical resu lts. J Vasc Surg 2001;
and 3-year longitud inal com p u ted tom ograp hy angiograp hy stu d y. J 33:1041–1049.
Vasc Surg 2001;33:S64–S69. 210. Bakker J, Goffette P, H enry M, et al. The Erasm e stu d y: a m u lticenter
186. Bad ran M, Gou ld D, Raza I, et al. Aneu rysm neck d iam eter after stu d y on the safety and technical resu lts of the Palm az stent u sed for
end ovascu lar rep air of abd om inal aortic aneu rysm s. J Vasc Interv the treatm ent of atherosclerotic ostial renal artery stenosis. Cardiovasc
Radiol 2002;13:887–892. Intervent Radiol 1999;22:468–474.
211. DeMaioribu s C, And erson C, Pop ham S, et al. Mycotic renal artery 232. Zeller T, Rastan A, Schw arzw ald er U, et al. Percu taneou s p erip heral
d egeneration and system ic sep sis cau sed by infected renal artery atherectom y of fem oropoliteal stenoses using a new -generation
stent. J Vasc Surg 1998;28:547–550. d evice: six-m onth resu lts from a single-center exp erience. J Endovasc
212. Deitch J, H ansen K, Regan J, et al. Infected renal artery p seu d o- Ther 2004;11:676–668.
aneu rysm and m ycotic aortic aneu rysm after p ercu taneou s translu - 233. Ram aiah V, Gam m on R, Kiesz S, et al. Mid term ou tcom es from the
m inal renal artery angiop lasty and stent placem ent in a patient w ith a TALON registry: treating perip herals w ith SilverH aw k: outcom es col-
solitary kid ney. J Vasc Surg 1998;28:340–344. lection. J Endovasc Ther 2006;13:592–602.
213. Bukhari R, Muck P, Schlueter F, et al. Bilateral renal artery stent infection 234. Conroy R, Gord on I, Tobis J, et al. Angiop lasty and stent p lacem ent in
and pseudoaneurysm formation. J Vasc Interv Radiol 2000;11:337–341. chronic occlu sion of the superficial fem oral artery: techniqu e and
214. H enry M, Am or M, H enry I, et al. Stents in the treatm ent of renal resu lts. J Vasc Interv Radiol 2000;11:1009–1020.
artery stenosis: long-term follow -u p . J Endovasc Surg 1999;6:42–51. 235. Dorros G, Jaff M, Dorros A, et al. Tibiop eroneal (ou tflow lesion)
215. Tu llis M, Zierler R, Glickerm an D, et al. Resu lts of p ercu taneou s trans- an giop lasty can be u sed as p rim ary treatm ent in 235 p atients w ith
lum inal angioplasty for atherosclerotic renal artery stenosis: a follow - critical lim b ischem ia: five-year follow u p . Circulation 2001;104:
u p stud y w ith d u p lex u ltrasonograp hy. J Vasc Surg 1997;25:46–54. 2057–2062.
216. Kashyap V, Sepu lved a R, Bena J, et al. The m anagem ent of renal artery 236. Faglia E, Mantero M, Cam initi M, et al. Extensive u se of p erip heral
atherosclerosis for renal salvage: d oes stenting help ? J Vasc Surg angiop lasty, particu larly infrap op liteal, in the treatm ent of ischaem ic
2007;45:101–109. d iabetic foot u lcers: clinical resu lts of a m u lticentric stu d y of 221 con-
217. H unink M, Donald son M, Meyerovitz M, et al. Risks and benefits of secutive d iabetic subjects. J Intern Med 2002;252:225–232.
femoropopliteal percu taneou s balloon angioplasty. J Vasc Surg 1993;17: 237. Giles K, Pom p oselli F, H am d an A, et al. Infrap op liteal angiop lasty for
183–194. critical lim b ischem ia: relation of TransAtlantic InterSociety Consen-
218. Stanley B, Teagu e B, Rap tis S, et al. Efficacy of balloon angioplasty of su s class to ou tcom e in 176 lim bs. J Vasc Surg 2008;48:128–136.
the superficial fem oral artery and pop liteal artery in the relief of leg 238. Ou riel K, Gray B, Clair D, et al. Com p lications associated w ith the u se
ischem ia. J Vasc Surg 1996;23:679–685. of u rokinase and recom binant tissu e p lasm inogen activator for
219. Golled ge J, Fergu son K, Ellis M, et al. Ou tcom es of fem orop opliteal catheter-d irected perip heral arterial and venou s throm bolysis. J Vasc
angioplasty. Ann Surg 1999;229:146–153. Interv Radiol 2000;11:295–298.
220. Johnston K. Fem oral and p op liteal arteries: reanalysis of resu lts of bal- 239. The STILE Investigators. Resu lts of a p rosp ective rand om ized trial
loon angioplasty. Radiology 1992;183:767–771. evalu ating su rgery versus throm bolysis for ischem ia of the low er
221. Bolia A, Miles K, Brennan J, et al. Percu taneou s translu m inal angio- extrem ity. Ann Surg 1994;220:251–268.
p lasty of occlusions of the fem oral and p op liteal arteries by subinti- 240. Ou riel K, Veith F, Sasahara A. A com p arison of recom binant u rokinase
m al d issection. Cardiovasc Intervent Radiol 1990;13:357–364. w ith vascular surgery as initial treatm ent for acute arterial occlu sion
222. Werner G, Ferrari M, Figu lla H . Su p erficial fem oral artery ru p tu re of the legs. N Engl J Med 1998;338:1105–1111.
after balloon angiop lasty: treatm ent w ith im p lantation of a balloon- 241. McN am ara T, Good w in S, Kand arp a K. Com p lications of throm boly-
exp and able graft. J Vasc Interv Radiol 1999;10:1115–1117. sis. Semin Interv Radiol 2000;11:134–144.
223. Cheng S, Ting A, Wong J. End ovascu lar stenting of su p erficial fem oral 242. Greenfield L, Proctor M. Filter com p lications and their m anagem ent.
artery stenosis and occlu sions: resu lts and risk factor analysis. Cardio- Semin Vasc Surg 2000;13:213–216.
vasc Surg 2001;9:133–140. 243. Joels C, Sing R, H aniford B. Com p lications of inferior vena cava fil-
224. Gord on I, Conroy R, Arefi M, et al. Three-year ou tcom e of end ovascu - ters. Am Surg 2003;69:654–659.
lar treatment of superficial femoral artery occlusion. Arch Surg 2001;136: 244. Reed R, Teitelbau m G, Taylor F, et al. Incom p lete op ening of LGM
221–228. (VenaTech) filters inserted via transju gu lar ap p roach. J Vasc Interv
225. Strecker E, Boos I, Gottm an D. Fem orop op liteal artery stent p lace- Radiol 1991;2:441–445.
m ent: evalu ation of long-term su ccess. Radiology 1997;205:375–383. 245. Rogers F, Strind berg G, Shackford S, et al. Five-year follow -u p of p ro-
226. Matsi P, Manninen H , Vanninen R, et al. Fem orop op liteal angiop lasty phylactic vena cava filters in high-risk trau m a p atients. Arch Surg
in patients w ith clau d ication: p rim ary and second ary p atency in 140 1998;133:406–412.
lim bs w ith 1–3-year follow u p . Radiology 1994;191:727–733. 246. Cam p bell J, Calcagno D. Aortic p seu d oaneu rysm from aortic p erfora-
227. Matsi P, Manninen H , Sod er H , et al. Percu taneou s translu m inal tion w ith a bird ’s nest vena cava filter. J Vasc Surg 2003;38:596–599.
angiop lasty in fem oral artery occlu sions: p rim ary and long-term 247. Raju S, Ow en S, N eglen P. The clinical im p act of iliac venou s stents in
results in 107 clau d icant p atients u sing fem oral and p op liteal the m anagem ent of chronic venou s insu fficiency. J Vasc Surg 2002;35:
catheterization techniqu es. Clin Radiol 1995;50:237–244. 8–15.
228. Lofberg A, Karacagil S, Lju ngm an C, et al. Percu taneou s translu m inal 248. Raju S, McAllister S, N eglen P. Recanalization of totally occlu d ed iliac
angiop lasty of the fem orop op liteal arteries in lim bs w ith chronic and ad jacent venou s segm ents. J Vasc Surg 2002;36:903–911.
low er lim b ischem ia. J Vasc Surg 2001;34:114–121. 249. Lam ont J, Pearl G, Patetsios P, et al. Prosp ective evalu ation of end olu -
229. van Lankeren W, Gu ssenhoven E, van Kints M, et al. Stent rem od eling m inal venous stents in the treatm ent of the May—Thu rner synd rom e.
contributes to fem oropop liteal artery restenosis: an intravascular Ann Vasc Surg 2002;16:61–64.
ultrasound stu d y. J Vasc Surg 1997;25:753–756. 250. Greenfield L, Proctor M, William s D, et al. Long-term exp erience w ith
230. Saxon R, Coffm an J, Good ing J, et al. Long-term resu lts of ePTFE transvenous catheter pu lm onary em bolectom y. J Vasc Surg 1993;18:
stent-graft versu s angiop lasty in the fem orop op liteal artery: single 450–458.
center experience from a p rosp ective, rand om ized trial. J Vasc Interv 251. Tim sit F, Reyn au d P, Meyer G, et al. Pu lm on ary em bolectom y by
Radiol 2003;14:303–311. cath eter d evice in m assive p u lm on ary em bolism . Chest 1991;100:
231. Du d a S, Bosiers M, Pu sich B, et al. End ovascu lar treatm ent of p eriph- 655–658.
eral artery d isease w ith expand ed PTFE-covered nitinol stents: 252. De Gregario M, Gim eno M, Mainar A, et al. Mechanical and enzy-
interim analysis from a p rosp ective controlled stu d y. Cardiovasc Inter- m atic throm bolysis for m assive p u lm onary em bolism . J Vasc Interv
vent Radiol 2002;25:413–418. Radiol 2002;13:163–169.
PART
Complications of
Gastrointestinal Surgery
CHAPTER
33
Complications of Gastric Surgery

Michael W. Mulholland
Gastric op erations constitu te an increasingly large p rop or- Desp ite stagnant overall m ortality rates, patients are
tion of the general su rgical w orkload . Although the inci- sp end ing less tim e in the hosp ital after gastric resection.
d ences of com plicated pep tic ulceration and gastric cancer The d ecrease in length of stay su ggests im p roved efficiency
have d eclined significantly over the past several d ecad es, and better u se of resou rces over tim e. Shorter hospital stays
gastric operations for treatm ent of m orbid obesity have m ay also resu lt from the cost-saving efforts of healthcare
und ergone exp losive grow th. Com plications from gastric p ayers d u ring the sam e interval (Fig. 33.3).
op erations are com m on and frequ ently severe. Laparoscopic approaches to gastric surgery are increas-
N ationw id e trend s for com plications of gastric su rgery ingly common. Laparoscopic gastric bypass has become
are clearest in how they relate to the treatm ent of gastric stand ard for the surgical treatm ent of morbid obesity. In
cancer. Ep id em iologic stu d ies in the United States d em on- adults, laparoscopic gastrectomy for treatment of gastric
strate that gastric cancer has d ecreased in incid ence over cancer is practiced in a few specialized centers. Laparoscopic
the last tw o d ecad es (1). Despite this red uction in inci- pyloromyotomy for pyloric stenosis has become widespread
d ence, gastric cancer rem ains one of the m ost com m on in pediatric surgical practice. Several studies comparing
cau ses of cancer-related d eaths in the United States, and open and laparoscopic pyloromyotomy have reported com-
surgical resection offers the only chance of cure (1–4). parable complication rates (6–8). A recent meta-analysis
In one recent study, the overall incidence of gastric cancer comparing these tw o approaches conclud ed that perforation
and subsequent gastric resection was reported to have and incomplete division of the hypertrophied muscle w ere
declined from 1988 to 2000 (5). Use of a nationwide database more frequent w ith laparoscopic pyloromyotom y (9). Oper-
has shown that the number of patients with a discharge diag- ative times w ere similar but time to oral feed ing and hospital
nosis of gastric cancer decreased from 25 cases per 100,000 stay w ere shorter w ith the laparoscopic method . Experience
U.S. adults in 1988 to 20 cases per 100,000 in 2000 (Fig. 33.1). is important. In a recent report, a 5.4-fold increased risk of
These results were mirrored by declining rates of gastric resec- mucosal perforation or incomplete pyloromyotomy w as
tion, with a 29% decrease from 5.6 cases per 100,000 adults in noted w hen the operation w as performed by a general sur-
1988 to 4.0 cases per 100,000 in 2000 (Fig. 33.1). The overall gery resid ent as compared to w hen performed by a more
proportion of hospitalized gastric cancer patients undergoing senior ped iatric surgery trainee (10).
gastric resection remained constant at approximately 22%.
Gastric resection for cancer has a relatively high rate of
postoperative complication and operative mortality. Inpa-
■ PEPTIC ULCERATION
tient mortality did not significantly change over the ■ Hemorrhage
1988–2000 timeframe, w ith an overall mortality rate of 7.4%
for the nationwide group. Rates of adverse outcomes were Although pep tic ulcer d isease rem ains a m ajor w orld w id e
not uniform but varied in relation to hospital experience with health p roblem , the United States has exp erienced a
the operation. Low volume centers had an 8.3% mortality d ecline in both the incid ence of u ncom p licated u lceration
rate, medium volume hospitals had a 7.1% mortality rate, and the rate of hosp italization for com p licated d isease (11).
and high volume centers had a 6.5% mortality rate (Fig. 33.2). Bleed ing, p erforation, and obstru ction are the three m ajor
The safety of gastric resection improved from 1988 to 2000 at com p lications of p ep tic u lcer, w ith bleed ing the m ost com-
high volume medical centers, with the mortality rate decreas- m on. Desp ite ap p reciation of the role of Helicobacter pylori
ing from 7.1% between 1988 and 1992, to 6.5% between 1993 infection in p ep tic u lcer p athogenesis and im p rovem ents in
and 1996, to 5.8% between 1997 and 2000. A decline in mor- therap eu tic end oscop y, m ortality from bleed ing ulcers has
tality w as not observed at low or medium volume hospitals. remained stable (8% to 10%) over the p ast 30 years (11–13).
Contem p orary patients are increasingly eld erly and fre-
quently have coexisting illnesses. Advanced age and the exis-
Michael W. Mulholland: Professor and Chairm an, tence of concurrent illness are the most important prognostic
Departm ent of Su rgery, University of Michigan Med ical factors in patients w ith bleeding peptic ulcers. Patients old er
School, Ann Arbor, MI than 60 years have a significantly higher m ortality than
393
394 Part V• Complications of Gastrointestinal Surgery
FIGURE 33.1. Incidence of gas- 6.0

tric cancer and gastric cancer resec- 29
tion in the United States, per 100,000 5.5
adults, from 1988 through 2000. 27
5.0 25
Gastric Cases of
4.5 23 gastric cancer
resections
21
4.0
Gastric resections 19
3.5 Cases of gastric cancer
17
3.0 15
99
0
90
89
91
92
95
96
8
93
84
97
98
0
8
19
20
19
19
19
19
19
19
19
19
19
19
19 Year
those you nger than 60 years. The p resence and num ber of is the most common cau se of chronic active gastritis, charac-
com orbid ities are closely related to m ortality (14–18). terized by nonerosive inflam m ation of the gastric m u cosa.
Antral gastritis is nearly alw ays p resent in p atients w ith
Pathogenesis d uod enal ulcer; H. pylori can be isolated from gastric
Infection w ith the gram -negative bacteriu m , H. pylori, is mucosa in most cases. Gastric metaplasia is very common in
very strongly linked to the d evelop m ent of p ep tic u lcera- the d u od enal ep itheliu m su rround ing areas of ulceration.
tion. This infectious association has fund amentally changed Because H. pylori bind s only to gastric-typ e ep ithelium ,
the treatm ent of p atients w ith p ep tic d isease. Althou gh m etap lastic gastric ep itheliu m can be colonized by H. pylori
H. pylori infection rates have w id e geographic variability, from gastric sou rces. Gastric m etap lasia of the d u od enal
the organism is present in as much as 30% to 50% of the bu lb is the m eans by w hich antral gastritis w ith H. pylori is
population. Most infected individuals remain without converted to active chronic d u od enitis. Erad ication of
sym ptom s; only 6% to 20% of colonized ind ivid uals d evelop H. pylori w ith antim icrobials lead s to u lcer healing rates
p ep tic u lcer d isease (19). Conversely, H. pylori is p resent su p erior to those seen w ith acid su p p ressing agents.
in 90% of patients w ith ulcer d isease. Surprisingly, the Relap se of d uod enal u lcer after antim icrobial therapy is
prevalence of H. pylori is 15% to 20% low er in patients w ith p reced ed by reinfection of the gastric mu cosa by H. pylori.
ulcer hem orrhage relative to patients w ith nonbleed ing Helicobacter pylori is the m ost com m on bacterial infec-
ulcers (4,20). The significance of this negative correlation is tion w orld w id e. H. pylori infection is u su ally acqu ired in
unknow n. child hood and lasts lifelong in the absence of specific ther-
Several d istinct observations suggest that H. pylori is a apy. Epid emiologic stud ies suggest the H. pylori infection
factor in the pathogenesis of d uod enal ulceration. H. pylori occurs via person-to-person contact, usually among family
9 40
8.3
8
7.1
7 6.5 30
6
In-hospital 5
20
mortality (%) 4 Length of
3 stay (days)
10
2
1
0 0
LVH MVH HVH
Hospital volume
−10
FIGURE 33.2. In-hospital mortality as a function of varying hospital volume. 1988–1992 1993–1996 1997–2000
Low hospital volumes are defined as performing four or fewer resections per Year
year. Medium volume hospitals are defined as performing five to eight resec-
tions per year. High volume hospitals are defined as performing nine or more FIGURE 33.3. Length of stay after gastric resection by time period from
resections per year. 1988 through 2000.
Chapter 33 • Complications of Gastric Surgery 395
members. Transmission is believed to occur d uring a bout of Table 3 3 .1 G a st r ic secr et or y r esp on ses t o
gastroenteritis; the highest risk is associated w ith vomiting. Helicobacter pylori in fect ion
Helicobacter pylori is the only hu m an bacteriu m know n
to infect the stom ach (21). To avoid the bactericid al activity Acid secretion
of the acid ic stom ach, the organism has evolved m echa- Increased basal acid output
nism s to m ove w ithin the gastric environm ent, to ad here to Increased maximal acid output
gastric m u cosa, and to abrogate the harm fu l effects of acid . Increased responsiveness to gastrin-releasing peptide
More than 300 genes of H. pylori are regulated by acid . Hormonal
All strains of H. pylori cau se p ersistent infection and all Increased basal gastrin levels
strains ind u ce gastric inflam m ation. Increased meal induced gastrin release
Bacterial viru lence factors inclu d ing vacu olating cyto- Decreased acid inhibition by cholecystokinin
toxin A (VacA) and cytotoxin-associated gene A (CagA) are Decreased antral distension inhibition of gastrin release
closely associated w ith the ability of H. pylori to cau se Duodenal bicarbonate secretion
mu cosal d am age (22). VacA is a pore-form ing cytotoxin of Decreased mucosal bicarbonate secretion
88 kilod altons. Up on release from the bacteriu m , the p ro-
tein m oves to the host cell m em brane w here it form s a ring
stru ctu re (22). The ring com plex inserts into the m em brane
of the host cell creating a pore. VacA p ores are perm eable to p rod u ction are m anifested clinically as elevated basal and
anions and sm all neutral m olecules, inclu d ing urea. m axim al acid ou tp u ts. Abnormalities in gastric secretion
VacA also inserts into end osom al m em branes lead ing to d isap p ear after H. pylori erad ication, su p p orting the id ea
osm otic sw elling. Pore form ation in m itochond rial m em - that infection is the cau se of increased acid p rod u ction (23).
branes ind u ces gastric cell d eath throu gh ap optosis. N onsteroid al anti-inflammatory d rugs (N SAIDs) are
The second m ajor viru lence factor in H. pylori is CagA. ubiquitous and have been associated w ith both gastric and
The CagA gene is p art of a region of DN A that is term ed a d uod enal ulcer d iseases. The inhibitory effect of NSAIDs
pathogenicity island . The genes ad jacent to the CagA gene upon prostaglandin production in the gastric mucosa is the
encod e proteins that function as m icroscopic need les for cause of N SAID ulcerogenic actions. NSAID use is an impor-
the transfer of bacterial p rod u cts into host gastric cells. tant risk factor for ulcer hemorrhage, and N SAIDs signifi-
After CagA p rotein is transferred to host cells, it cantly increase the risk of bleed ing in H. pylori–infected
becom es p hosp horylated on tyrosine resid ues by host cell individ uals (24). Ingestion of NSAIDs is associated with a
kinases. Phosp horylated CagA activates a nu m ber of cellu - tw ofold increase in risk of bleed ing in patients w ho are
lar signaling pathw ays involved in cellu lar polarity, infected with H. pylori relative to patients w ho are H. pylori-
cytoskeletal p rotein fu nction, and cellular p roliferation and negative (17). Only 10% of patients w ith bleed ing ulcers are
d ifferentiation. Infected gastric cells becom e m ore elon- both H. pylori-negative and without a history of NSAID
gated , ap ical ju nctions betw een cells are d isrup ted , gap s exposure (20).
d evelop betw een epithelial cells, and epithelial barrier
fu nction is lost. Distu rbance of cellu lar fu nction p rom otes Endoscopic Treatment
ap op tosis, affects epithelia restitu tion, and m ay inhibit Pep tic ulcer d isease constitu tes a significant prop ortion of
ulcer healing. u p p er gastrointestinal (GI) hem orrhage. A w id ely variable
With m u cosal colonization, a variety of bacterial and p rop ortion of p atients (20% to 68%) p resent w ith m elena,
host resp onses are elicited . H. pylori prod u ces the enzym e w hile 14% to 30% d evelop hem atem esis and 18% to 50%
urease. Urease hyd rolyzes u rea to prod u ce am m onia, p resent w ith both hem atem esis and m elena (11,13,25). Ini-
w hich, in tu rn, increases lu minal pH , thu s provid ing a tial m anagem ent is focu sed on stabilization and then upon
favorable m icroenvironm ent for H. pylori survival. Urease d iagnosis. Patients shou ld be aggressively resu scitated
prod u ction ap p ears to be crucial to the pathogenicity of w ith intravenou s flu id s and blood com p onents. Patients
H. pylori; mu tants of H. pylori that d o not prod uce urease are p resenting w ith shock, eld erly p atients ( 60 years), and
unable to establish colonization. The bacteriu m attaches to those w ith recu rrent bleed ing are at increased risk of d eath
the gastric ep itheliu m beneath the m ucous layer. Follow ing and shou ld be treated in an intensive care u nit (14–18). A
attachm ent, H. pylori cau ses d irect cellular injury and nasogastric tu be shou ld be inserted and the stom ach
changes gastric secretory physiology. lavaged w ith w arm saline. Lavage is not effective in stop-
H. pylori infection prod uces abnorm alities in gastric p ing bleed ing; it is perform ed to allow subsequ ent end o-
acid secretion (Table 33.1). Levels of seru m gastrin are ele- scop ic visu alization of the bleed ing site. The use of
vated in p atients infected w ith H. pylori. H yp ergastrinem ia intravenou s histam ine2-blockers for acu te u lcer bleed ing
second ary to H. pylori infection occu rs in resp onse to the has not been show n to be beneficial (11,26,27). Proton
cytokines tu m or necrosis factor- and interleu kin-8, w hich p u m p inhibitors m ay imp rove ou tcom es in patients w ith
are p rod u ced in resp onse to m u cosal infection. Local bleed ing u lcers (28–30). H ow ever, these d ru gs shou ld not
secretion of the inhibitory horm one som atostatin is also be consid ered the cru cial asp ect of therap y d u ring the acu te
d im inished . The imbalances in gastrin and som atostatin episod e.
Table 3 3 . 2 En d oscop ic u lcer a p p ea ra n ce a n d and su rrou nd ing blood vessels. A d ilu te solu tion (1:10,000)
r isk of r ecu r r en t h em or r h a ge of ep inep hrine is m ost com m only u sed for this p u rp ose.
Other injection agents inclu d e p olid ocanol, ethanol, and
Risk Appearance Recurrent Bleeding throm bin. With either heater p robe or injection, the initial
Low Clean base 0%–15% su ccess rate is estim ated at 75% to 90% (26,34,35). Com pli-
Flat spot cations, either im med iate bleed ing or p erforation, have
High Adherent clot 40%–90% been reported in 1% of cases (11,34).
Nonbleeding visible vessel The m ajor com p lication of end oscopic therapy is
Active hemorrhage d elayed rebleed ing, occurring after approximately 10% to
30% of initial end oscopic hemostasis cases (11,25,26,36).
Alm ost all patients w ho rebleed after end oscopic therapy
d o so w ithin 96 hours of the initial end oscopic proced ure
Up p er GI end oscopy, not contrast rad iography, is the (25). In one report, all fatal rebleed ing events occurred
preferred d iagnostic m od ality for u pper GI hem orrhage. w ithin the first 24 hou rs of the initial bleed ing episod e (37).
End oscop y can d efine the natu re and site of the bleed ing H igh-risk patients includ e those w ith hemod ynamic insta-
lesion. End oscop ic find ings also provid e inform ation that bility, com orbid d isease, or visible u lcer vessels, and they
pred icts the risk of recurrent bleed ing (Table 33.2). End o- should be m onitored in an intensive care u nit. Patients w ith
scopic therap y, p erform ed im m ed iately, d efines the natu re limited bleed ing and low risk find ings, such as a clean ulcer
of the bleed ing lesion and is effective in m ost p atients base on end oscopy, m ay be d ischarged w ithin 24 hours.
( 80%). When necessary, tissu e biopsy can be obtained for Surgery has been the usual treatment in case of failure of
histology and for the d iagnosis of H. pylori infection. end oscopic therapy. Recent d ata suggest that end oscopic
End oscopy should not be performed until patients have retreatment is also a safe alternative (36). Endoscopic retreat-
been hem od ynamically stabilized . Follow ing resuscitation, ment has a success rate of 50% to 70% in patients w ho
end oscop y should be p erform ed em ergently in high-risk rebleed after initial endoscopic therapy. Endoscopic retreat-
patients such as the eld erly, those w ith significant blood ment m ust be employed w ith caution. The perforation rate
loss, and patients experiencing rebleed ing ep isod es. Perfor- d uring end oscopic retreatment is increased , and a significant
mance of initial end oscopy w ithin 24 hours of the bleed ing d elay in d efinitive therapy must not occur for those patients
ep isod e has been associated w ith im proved outcom e (31). w ho fail the second attempt at end oscopic hemostasis.
The end oscop ic ap p earance of the u lcer bed and u lcer Surgical treatment of rebleeding should be considered
size p rovid e inform ation that p red icts the likelihood of for patients w ho are at highest risk for continued bleed ing,
rebleed ing. Ulcers are categorized on the basis of end o- includ ing patients w ith large ulcers and large bleed ing ves-
scopic ap p earances: clean base, flat sp ot, ad herent clot, sels, the elderly ( 60), patients w ith active hemorrhage, and
nonbleed ing visible vessel, or active bleed ing. Each of these patients who develop hypotension. These factors have been
appearances is associated w ith a d efined risk of rebleed ing associated with failure of endoscopic therapy (14,37,38).
(Table 33.2). Althou gh patients w ith clean base u lcers have
a very low recu rrent bleed ing rate, those w ith visible ves- Operative Treatment
sels or active bleed ing have recu rrent bleed ing rates of 43% Operative therapy is ind icated w hen end oscop ic therap y is
and 55%, resp ectively (4,32–34). Becau se of the risk of either not p ossible or u nsu ccessfu l or w hen bleed ing is so
recurrent hem orrhage associated w ith these end oscopic rap id that end oscop y is not feasible. Becau se the ind ica-
find ings, p atients w ho have a nonbleed ing visible vessel or tions for su rgical therapy are id entical to those for end o-
active bleed ing at the tim e of end oscopy shou ld und ergo scop ic therap y, a su rgeon shou ld be consu lted for the care
im med iate end oscop ic therapy (34). For patients w ith low of every p atient w ith u p p er GI hem orrhage from the ou t-
risk visu al find ings, end oscopic therap y is not recom - set (Table 33.3). Patient characteristics su ch as ad vanced
m end ed , as intervention has not been show n to red uce the age ( 60 years) and the p resence of significant com orbid
alread y low risk of rebleed ing (34).
End oscopic therapy options inclu d e therm al coagu la-
tion and injection of vessel sclerosants or vasoconstrictor
Table 3 3 .3 In d ica t ion s for op er a t ion in bleed in g
agents. Thermal coagu lation involves d irect application of
p ep t ic u lcera t ion
heat or electrocoagu lation to the bleed ing site. The electro-
coagu lation d evice or heat p robe is p assed throu gh the Continuous or recurrent hemorrhage
end oscope and positioned so that it overlies the visible Ongoing transfusion requirement
bleed ing vessel. Initial hem ostasis is accom plished by
Hypotension
d irect vessel com p ression w ith coap tation of vessel w alls.
Energy is ap p lied to p rod u ce tissu e coagu lation. Age 60 years with ongoing hemorrhage
End oscop ic injection therapy involves injection of solu - Failed endoscopic hemostasis
tions into the base of the ulcer, resu lting in tam ponad e, Ulcer inaccessible to endoscopic therapy
vasoconstriction, and eventual sclerosis of the u lcer bed
FIGURE 33.4. Operative maneu-

vers in management of bleeding
duodenal ulcer. A: The duodenum is
mobilized from the retroperitoneum
by a Kocher maneuver. B: As the
duodenum is reflected anteriorly,
the retroperitoneal duodenum, the
posterior aspect of the pancreatic
Foramen head, and the inferior vena cava are
of Winslow visualized. C: Direct visualization of
the ulcer is obtained by a longitudi-
nal duodenotomy. D: Circumferen-
tial sutures are used to control
vessels entering the ulcer base
Lateral peripherally. Vessels entering per-
peritoneal pendicularly are controlled using a
reflection Duodenum U-stitch.
Inferior
vena cava
Pancreas
A
B
Inferior
vena cava
Ulcer
Ulcer
Duodenum Clot
Duodenotomy
HRF '04
C D
d isease p red ict a superior ou tcom e w ith early su rgery For bleed ing d u od enal u lcers, a Kocher m aneu ver is
(18,26). Eld erly p atients or those w ith card iovascu lar com - first p erform ed to m obilize the d u od enu m from the
prom ise cannot su stain repetitive hypotension or the retrop eritoneu m (Fig. 33.4). Throu gh a d u od enotom y, the
episod ic anem ia related to d elayed su rgical therapy. bleed ing vessel at the base of the u lcer is visu alized and lig-
When su rgery is performed for hemorrhage, there are ated . In p lacing su tu res, care shou ld be taken to avoid the
tw o therapeutic goals. First, the bleed ing must be concom m on bile d u ct as it p asses d eep to the first and second
trolled . Second , therapy that minimizes ulcer recurrence p ortions of the d u od enu m .
should be provid ed . Direct suture ligature of the ulcer or After hem ostasis is achieved , a d ecision m u st be m ad e
bleed ing site is used to control hemorrhage. When the site abou t the p erform ance of a d efinitive antiu lcer proced ure.
of ulcer bleed ing is a gastric ulcer, the ulcer should be The su rgical literatu re on this issu e p red ates the cu rrent
resected . In ad d ition to hemostasis, ulcer resection provid es u nd erstand ing of the p athogenetic role of H. pylori in u lcer
gastric tissu e for histology to evaluate for the presence of d isease. Cu rrently available bu t d ated literature su ggests
gastric cancer. For ulcers located on the lesser curve of the that the perform ance of an antiu lcer proced u re in ad d ition
stomach near the gastroesophageal junction, resection may to oversew ing the ulcer prod u ces a low er rate of rebleed ing
be hazard ous and d irect su ture ligatu re of the ulcer base is com p ared to oversew ing of the u lcer alone. Postoperative
more appropriate, w ith biopsy to exclud e cancer. m orbid ity and m ortality are rep orted to be sim ilar (39,40).
Table 3 3 .4 Resu lt s of elect ive op era t ion for control grou p s. Tw o ad d itional trials have comp ared recur-
p ep t ic u lcer rent bleed ing d u ring maintenance ranitid ine therapy (11%
to 13%) to bleed ing su bsequ ent to H. pylori erad ication (2%
Procedure Mortality Recurrent Ulcer Dumping to 5%) (48,49). Althou gh it seem s likely that effective antibi-
Truncal vagotomy 1% 10%–12% 1%–10% otic therap y w ou ld elim inate d u od enal u lcer d isease in
p ostop erative p atients and thu s p erm it m ore lim ited su rgi-
Proximal gastric 0.5% 8%–20% 2%–3%
vagotomy cal therap y for control of hem orrhage, this ap p roach has
not yet been su bjected to clinical trial.
Truncal vagotomy and 1% 1% 10%–20%
antrectomy
■ Perforation
H osp italization rates for d u od enal u lcer p erforation have
H ow ever, these stu d ies are flaw ed in that they d o not not d ecreased w ith the introd u ction of p ow erfu l antisecre-
ad d ress the effect of H. pylori erad ication on bleed ing recu r- tory d ru gs or w ith antibiotic treatm ent of p ep tic u lcer. In
rence after su rgery. the m ajority of affected p atients, p erforation is the first
In the past, vagotom y and pyloroplasty had been recom - m anifestation of d u od enal u lcer d isease.
mend ed in hemod ynamically unstable patients w hen the The patient usually experiences sud d en, severe epigas-
operative goals need to be achieved exped itiously. When tric pain, follow ed shortly by diffuse abdominal pain. Chem-
performed electively, operative mortality approximates 1% ical irritation of the parietal peritoneum by acid ic gastric
and ulcer recu rrence rates average 10% to 12% (Table 33.4). contents causes severe pain. If there is contact between the
The incid ence of d u mping, a synd rome of postprand ial gastric contents and the d iaphragm, the patient w ill also
flushing and vasomotor effects, ranges from 1% to 10% experience referred pain in the area of the right scapula. Res-
(41,42). Elective highly selective vagotomy is also associated piration w orsens symptoms. Physical examination typically
w ith low mortality but w ith somew hat higher recurrence reveals a silent abdomen w ith muscular rigid ity and epigas-
rates of 10% to 15%. In most series, highly selective vago- tric tenderness. Moderate fever and tachycardia are often
tomy has few er postoperative symptoms, w ith an incid ence present; hypotension is initially unusual. Laboratory exami-
of d umping of 5%. Elective vagotomy and antrectomy is nation reveals leukocytosis. H yperamylasemia, attributed to
associated w ith an u lcer recu rrence rate of 1% (41,42). absorption of d uod enal contents from the peritoneal cavity,
N ot su rp risingly, surgical results are less salutary w hen is common. Upright abd ominal films d emonstrate pneu-
hem orrhage p rom p ts u rgent operation. When perform ed moperitoneum in 80% of cases. If pneumoperitoneum is
em ergently, vagotom y and pyloroplasty has a recu rrent absent, computed tomography (CT) w ith oral contrast may
bleed ing rate of 17%, w ith a d uod enal leak rate of 3%. be used to d emonstrate perforation.
Vagotom y and gastrectom y has a low er rebleed ing rate of The fasting hu m an stom ach contains 102 to 103 organ-
3%, bu t a significantly higher frequency of d uod enal leak at ism s; oral bacteria, inclu d ing lactobacilli and aerobic strep-
13%. Rates of reop erations for bleed ing and overall m ortal- tococci, p red om inate. Infectiou s com p lications associated
ity are sim ilar for these tw o proced u res (43). w ith d u od enal p erforation are closely related to the length
Prevention of recu rrent bleed ing requ ires treatm ent of tim e that elap ses before d efinitive treatm ent. Peritoneal
of u nd erlying H. pylori infection and d iscontinu ation of cu ltu res obtained betw een 6 to 12 hou rs of p erforation are
N SAIDs. With anti-H. pylori therap y and avoid ance of p ositive in 50% of cases, bu t cu ltu re p ositivity increases
N SAIDs, a 95% u lcer cu re rate for u ncom p licated p ep tic rap id ly thereafter. Beyond 24 hou rs coliform s and fu ngal
ulcers has been rep orted . The com bination of om ep razole, sp ecies are increasingly frequ ent.
am oxicillin, and clarithrom ycin has been m ost w id ely u sed Nonoperative management of perforated duodenal ulcer
and is associated w ith elim ination of H. pylori in 90% of is rarely justified in mod ern medical practice. Reports of non-
patients. An alternative regim en com bines om eprazole, operative management are highly biased by exclusion of
metronid azole, and either am oxicillin or clarithrom ycin. patients with gastric ulcer, perforations of 24 hours dura-
When N SAIDs cannot be d iscontinued , use of the synthetic tion, clinical deterioration, associated shock, diagnostic
prostagland in analog Misop rostol d ecreases the incid ence uncertainty, or comorbid med ical illnesses (50). In one report,
of recu rrent bleed ing, especially in the eld erly (44,45). initial treatment with intravenous fluids, nasogastric suction,
Data from a num ber of controlled trials are now avail- and antibiotics was coupled w ith contrast rad iography to
able, d em onstrating that for patients w ith bleed ing as a evaluate for intraperitoneal leakage of gastric contents. Lack
com plication of H. pylori-positive u lcers, erad ication of of clinical improvement was an indication for emergent oper-
infection p revents recurrent u lceration and bleed ing. Tw o ation. In this series, 28% of patients initially managed nonop-
rand om ized trials have reported the resu lts of treatm ent of eratively had clinical deterioration within 24 hours, and
H. pylori in patients follow ing d uod enal u lcer hem orrhage perforated neoplasms were discovered in 27% of patients ini-
(46,47). Patients treated w ith antibiotics had a 0% incid ence tially treated for perforated ulcers. Older patients were less
of recurrent bleed ing d uring the year follow ing treatm ent, likely to improve with nonoperative treatment. Hospitaliza-
w hile 33% and 27% rates of repeat bleed ing w ere noted in tion was 35% longer in the group treated nonoperatively.
Risk factors that pred ict op erative m ortality inclu d e con- scop ically treated p atients, the m ore im p ortant variable of
current med ical comorbid ity, preoperative shock, and long- hosp ital length of stay w as not significantly shorter for
stand ing p erforation ( 48 hours) (51). If these factors are these p atients. Overall rates of p ostop erative com plications
absent, ulcer operation may be p erformed w ith pred ictably w ere not statistically d ifferent for the tw o approaches. A
low mortality and accep table morbid ity. If one or more risk low er rate of w ou nd infection in the lap aroscop ic grou p
factors are present, the risk of d eath increases progressively. ap p roached significance. Retu rn to norm al d aily activities
Patients w ith zero, one, tw o, or three risk factors have been and w ork favored the lap aroscop ic grou p . The p ooled esti-
rep orted to have m ortality rates of 0%, 10%, 46%, and 100%, m ate of m ortality favored lap aroscop ic rep air.
respectively (51). In a recent m ultivariate analysis, age 65 Om ental p atch closu re of p erforated d u od enal u lcer
years, American Society of Anesthesiologists (ASA) stage III alone is not ad equ ate treatm ent. Becau se the und erlying
or IV, and a d elay of surgery beyond 24 hours after onset of u lcer d iathesis is not altered , sim p le p atch closu re is fol-
symptoms pred icted mortality (52). When all three risk fac- low ed by an u lcer recu rrence rate of 61% at a mean of
tors w ere p resent, m ortality w as 61%. 20 m onths (47). H. pylori erad ication follow in g om ental
Op erative treatm ent of p erforated d u od enal u lcer has p atching red u ces u lcer recu rrence to 5%.
fou r goals: p atient safety, peritoneal d ebrid ement, closu re Com p lications are m ore frequ ent and m ore severe
of the p erforation, and alteration of the u lcer d iathesis so w hen large d u od enal d efects or p enetration into other
that the risk of recurrent u lceration is m inim ized . For m ost organs requ ire resectional therap y. Postop erative morbid -
patients p eritoneal cleansing can be achieved by either ity has been rep orted in 9% of p atients w ith sm all anterior
lap aroscop y or laparotom y. Lap aroscop ic closu re of d u o- p erforations and in 22% to 34% of those w ith com plicated
d enal p erforation is u su ally confined to those w ith a soli- d efects (56).
tary p rep yloric u lcer located anteriorly (52). Most rep orts
of lap aroscop ic rep air have em p loyed either om ental Postoperative Hemorrhage
patching or fibrin glu e rep air. Perforated ulcers w ith larger Unrecognized injury to the spleen is the most common cause
d efects or those w ith d estru ction of the p roxim al d u od e- of postoperative hemorrhage after operations on the stom-
nu m or p enetration into ad jacent organs requ ire lap aro- ach or d uod enum. Splenic hemorrhage occurs as a result of
tomy and resectional therapy. capsular injury from traction on splenic attachments or from
Laparoscopic repair of duodenal perforation and open inappropriately placed retractors. Failure to properly ligate
repair have been compared in two prospective trials (53,54). short gastric vessels during dissection of the greater curva-
Laparoscopic repair requires significantly longer operative ture of the stomach can also lead to splenic hemorrhage. In
time (Table 33.5). Postoperative analgesic requirements are several series of splenectomy, inad vertent injury d uring
fewer with laparoscopy. No significant differences were noted upper abd ominal surgery is among the most common ind i-
between these techniques in duration of nasogastric suction, cations for splenectomy. In ad d ition to the d angers of hypo-
intravenous infusion, and hospital stay; time to resumption of volemia, splenectomy increases the incidence of pancreatic
oral diet; reoperation rate; morbidity; or mortality. fistula, pancreatitis, and septic complications, including sub-
Tw o m eta-analyses of su rgical treatm ent of p erforated phrenic abscess. Follow ing vagotomy, vessels in proximity
peptic u lcer have com pared open surgical therap y w ith to the esophagus may be the source of bleeding.
lap aroscop ic ap p roaches (22,55). In term s of operative tim e, Intralu m inal hem orrhage m ost com m only rep resents
there is no clear su periority of one approach over the other, su tu re line bleed ing from su bm u cosal arterioles and
bu t all trials rep orted after 2001 have favored laparoscop ic veins. Gastric lavage w ith w arm ed saline via the nasogas-
rep air. While analgesic u se in hospitals is less for lap aro- tric tube is used to clear the stom ach of clots as a prelu d e to
end oscop y. End oscop ic hem ostasis, sim ilar in technique to
that d escribed for bleed ing u lcers, is u su ally successfu l.
Table 3 3 .5 Com p a r ison of la p a roscop ic a n d op en Uncontrolled hem orrhage is an ind ication for reoperation.
r ep a ir of p er fora t ed d u od en a l u lcer
Gastric Outlet Obstruction
Mortality Similar
Gastric outlet obstruction and sm all bow el obstruction are
Morbidity Similar
relatively frequ ent follow ing gastric resection, occurring in
Analgesics requirements Less for laparoscopy 3% to 5% of cases. The m ajor cau se of anastom otic obstruc-
Operative time Shorter for laparotomy tion in the early p ostoperative period is inflam m ation ad ja-
Duration of NG suction Similar cent to the anastom osis, second ary to su bclinical su ture
line leakage or ischemia. Chronic gastric outlet obstruction
Duration of IVinfusion Similar
is often the consequence of perianastomotic ulceration w ith
Time to oral intake Similar resu ltant cicatrization. Pain is not u su ally prom inent in gas-
Hospital stay Similar tric ou tlet obstru ction. Recurrent vom iting or p ersistently
Reoperation rate Similar elevated nasogastric tu be ou tp u t su ggests the d iagnosis.
Fiberop tic end oscop y shou ld be u sed w hen gastric ou tlet
NG, nasogastric; IV, intravenous. obstru ction is consid ered to evalu ate anastom otic patency.
If the p atient has a Billroth II anastom osis, the patency of transverse m esentery to the stom ach at least 2 cm su perior
each lim b m u st be evaluated . An open anastom osis favors to the anastom osis. The exp osu re for this m aneu ver is best
d elay in reop eration and su p p ort of nu tritional need s w ith achieved inferior to the transverse colon. Volvu lus of the
p arenteral alim entation. p roxim al or d istal lim bs of the gastrojeju nostom y is possi-
Mechanical sm all bow el obstru ction m ay occu r follow - ble follow ing Billroth II reconstru ction, m ore comm only
ing Billroth II gastrojeju nostom y, perform ed either retro- w hen the anastom osis is antecolic.
colic or antecolic. When gastrojejunostom y is perform ed in The afferent loop syndrome is a cond ition caused by par-
a retrocolic p osition, obstru ction m ay be d u e to occlu sion of tial obstruction of the proximal limb of a gastrojejunostomy.
the anastom osis by the transverse m esocolon (Fig. 33.5). Obstruction may be caused by kinking or torsion of the anas-
The stom ach m ay retract upw ard , resulting in pinching of tomosis, obstruction by the transverse mesentery, internal
one or both jeju nal lim bs by a relatively unyield ing m esen- hernia, or recu rrent u lceration (Fig. 33.6). Partial obstruc-
tery. This com p lication m ay be avoid ed by suturing the tion resu lts in interm ittent d ilatation of the d u od enu m and
Transverse
colon Avascular
area
Middle
colic artery
Ligament
of Treitz
Jejunum
A HRF '04
Incisions
Posterior
mucosal suture
Posterior Anterior
serosal suture mucosal suture
Stay suture
Jejunum
'04
C
HRF
B
FIGURE 33.5. Construction of gastrojejunostomy. A: The transverse colon is retracted upward, and the vascular arcades within the
transverse mesocolon are identified. An avascular area to the left of the middle colic vessels is chosen as the site for incision. An incision
large enough to deliver the jejunum to the stomach is created. B: Interrupted 3-O seromuscular sutures are placed and tied. Electro-
cautery is used to create equal length incisions in the stomach and jejunum. C: A continuous mucosal suture of absorbable material is
begun posteriorly and is continued along the anterior portion of the anastomosis.
Transverse
mesentery
defect
Jejunum
04
HRF '
D Seromuscular suture E
FIGURE 33.5. (Continued ) D: Interrupted seromuscular sutures are used to complete the anterior portion of the double layer of
anastomosis. E: The completed gastrojejunal anastomosis should be positioned beneath the transverse mesocolon to prevent angu-
lation or obstruction of the efferent or afferent jejunal limbs. The mesenteric defect is secured through the gastric wall with inter-
rupted sutures.
FIGURE 33.6. Afferent loop obst-

ruction can be caused by kinking at
the gastrojejunal anastomosis.
HRF '04
proximal jejunum, with periodic release of pancreatic and hyp om otility. Rad ionu clid e solid p hase gastric em p tying
biliary secretion into the stomach. Afferent loop obstruction stu d ies are u sed to evalu ate gastric fu nction and to p ro-
occurring in the immed iate postoperative period causes vid e a qu antitative m easu re of the effectiveness of m ed -
severe and unrelenting epigastric pain. Acute afferent loop ical therap y.
obstruction is a surgical emergency because, if unrelieved , End ocrine d istu rbances can cau se d isord ered gastric
obstruction can cause d uod enal stump leakage. The d ilated em p tying. H yp othyroid ism and d iabetes m ellitu s are
loop can be visualized on abdominal CT scan; the obstructed p rom inent exam p les. A variety of d iseases, inclu d ing am y-
limb will not contain orally ingested contrast. Mechanical loid osis, sclerod erm a, m u scu lar d ystrop hy, m yasthenia
stasis in the d u od enu m m ay cau se elevation in seru m gravis, and p soriasis, can alter gastric em p tying. Med ica-
am ylase valu es and m ay be confu sed w ith p ostop erative tions that affect gastric em p tying shou ld be d iscontinu ed ,
p ancreatitis. Acute afferent loop obstruction requires urgent inclu d ing narcotics, anticholinergics, and L-d op a. Patients
reoperation because of the possibility of perforation. shou ld receive a p rolonged trial of p rokinetic d ru g therap y.
Jeju n ogastric in tu ssu scep tion is an u n u su al cau se of Patients w h o m eet these criteria an d fail to resp ond
gastric outlet obstruction, occurring in 1% of cases (57). In to aggressive m ed ical m anagem ent are cand id ates for
more than three-fourths of patients, the efferent limb is the op erative treatm en t. Total or near-total gastrectom y w ith
source of the intussusception. Urgent endoscopy reveals a fri- Rou x-en -Y gastrojeju nostom y h as been rep orted as a
able, bluish mass originating from the orifice of the efferent treatm ent for p ostsu rgical gastrop aresis (58). At a m ean
limb. Abdominal CT scan demonstrates a mass w ithin the follow -u p of 56 m onths, 78% of p atients rep orted sym p to-
stomach with a layered, onion-skin-like appearance. Urgent m atic im p rovem ent. For 7% of p atients there had been no
operative reduction of the intussusception is indicated due to change in their cond ition, and for 15% sym p tom s had
the potential for ischemic necrosis of the intussusceptum. w orsened . N o p ostop erative d eaths w ere rep orted for
52 p atients. Postop erative com p lications w ere noted in
Postsurgical Gastroparesis 29%, w ith w ou nd infection, p rolonged ileu s, and p neu m o-
Postsu rgical gastrop aresis is a chronic com plication of gas- nia the m ost frequ ent.
tric su rgery characterized by d isru p tion of the norm al
mechanism s of gastric m otility (58). Affected patients have Duodenal Fistula
postprand ial p ain, nau sea, and vom iting; m ost have d iffi- Duod enal fistula m ay be a com plication of gastric resec-
cu lty m aintaining ad equate oral nutrition. The incid ence of tion, p articu larly w hen the d u od enu m is closed and gastro-
motility d istu rbances follow ing gastric su rgery is poorly jeju nal reconstru ction p erform ed . The d u od enal stu mp
d efined ; abnorm alities in gastric em ptying have been m ay d ehisce at the site of closu re, an end fistu la, or the d u o-
record ed in 30% of p atients follow ing truncal vagotom y d enu m m ay p erforate laterally, cau sing a lateral fistu la.
and Rou x-en-Y gastrectom y (58–60). Duod enal fistulas are p articularly m orbid becau se of the
The p athogenesis of p ostsu rgical gastrop aresis is high flu id volu m e lost and becau se of the escap e of p ancre-
u nknow n. Lack of vagal tone, abnormalities of neuromus- atic and biliary secretions into the p eritoneal cavity. Once
cular coord ination, d isord ered smooth muscle function, and fistu lization has occu rred , attem p ts at im m ed iate operative
motor abnormalities of the Roux-en-Y limb have been postu- closu re are fu tile. Initial m anagem ent is concerned w ith
lated but remain unproven. Histologic examination of the treatm ent of sep sis, control of intrap eritoneal leakage, and
dysfunctional stomach usually reveals no abnormality (58). skin p rotection at any site of external d rainage. Percuta-
The d iagnosis of p ostsu rgical gastrop aresis requ ires neou s transhep atic d u od enal d rainage has been rep orted
the absence of anatom ic obstru ction, inclu d ing anasto- as a m ethod to externally d rain p ancreatic-biliary secre-
m otic strictu re and efferent lim b obstruction (Table 33.6). tions in the p resence of d u od enal fistu lization (61). Par-
Fiberoptic end oscop y of the gastric rem nant is a strict enteral alim entation is necessary to m aintain a p ositive
requ irem ent. Contrast stu d ies of the sm all intestine are u se- nitrogen balance in the w eeks requ ired for sp ontaneou s
fu l to exclu d e d istal obstru ction or generalized intestinal closu re or reop eration. When d istal obstru ction exists in
the afferent jeju nal lim b, sp ontaneou s fistu la closure w ill
not occu r.
Table 3 3 . 6 Req u ir em en t s for d ia gn osis of If sp ontaneou s closu re d oes not occu r w ithin 6 w eeks,
p ost su r gica l ga st r op a r esis op erative rep air is ju stified . If a p ortion of the d u od enum is
m issing or nonviable, d u od enal reconstru ction is required .
1. Prior history of gastric resection, usually with vagotomy The m ost w id ely accepted m ethod is constru ction of a
2. Upper endoscopy to exclude anastomotic obstruction, efferent limb Rou x-en-Y jeju nal segm ent to close the d u od enal d efect via
obstruction, jejunogastric intussusception a fu nctional sid e-to-end d u od enojeju nostom y.
3. Exclusion of hypothyroidism, diabetes mellitus
4. Exclusion of medical disorders such as scleroderma, amyloidosis, mus- Avulsion of the Sphincter of Oddi
cular dystrophy
5. Contrast study of small intestine Operative inju ry to the am pu lla of Vater is a serious bu t
6. Solid phase gastric emptying study rare event d u ring gastric resection. Inju ry to this area is
p ossible d uring any operation on the d uod enu m bu t is
Table 3 3 . 7 Fea t u r es of ea r ly d u m p in g syn d rom e

Cardiovascular Gastrointestinal
Tachycardia Nausea
1 Palpitations Colic and cramping
2 Dizziness Abdominal pain

Syncope Diarrhea
Sweating
Flushing
3
4
m ent in ap p roxim ately 60% (63). The som atostatin ana-

logu e octreotid e has been reported to im prove d u m ping
sym p tom s w hen 50 to 100 g is ad ministered subcuta-
neou sly p rior to a m eal. The beneficial effects of octreotid e
on vasom otor sym p tom s of d u m p ing are d u e to p ressor
FIGURE 33.7. Avulsion of the ampulla of Vater demonstrated by percuta-
effects of the com pou nd on splanchnic vessels and inhibi-
neous transhepatic cholangiography (PTC). Injection of the PTC catheter tion of the release of vasoactive p ep tid es from the gu t.
demonstrates free flow of contrast into the subhepatic space. The common Octreotid e also d ecreases p eak p lasm a insu lin levels and
biliary-pancreatic channel also provides a pancreatogram. Severe inflamma- slow s intestinal transit. The system ic effects of octreotid e
tory changes in the subhepatic space were treated by external drainage and
parenteral hyperalimentation. The patient ultimately required pancreatico- inclu d e blu nting changes in p u lse, systolic blood pressure,
duodenectomy for correction of the defect. 1, common bile duct; 2, cystic duct and p acked red cell volu m e d u ring early d u m ping and pre-
stump; 3, subhepatic collection; 4, pancreatic duct. venting d ecreases in seru m glu cose concentration d u ring
late d um ping.
most frequent in the presence of scarring or inflam m ation Cancer in the Gastric Remnant
that cau ses second ary shortening of the d u od enal bu lb
(62). The inju ry occu rs d u ring d issection betw een the d u o- A grow ing nu m ber of rep orts su ggest that gastric cancer is
d enu m and p ancreas p rior to d u od enal transection. Most m ore likely to d evelop in ind ivid u als w ho have u nd ergone
injuries can be recognized by the su d d en appearance of bile p reviou s p artial gastrectom y. The clearest risk factor for the
in the op erative field . Postoperatively, the injury cau ses col- d evelop m ent of gastric cancer after gastrectom y is the tim e
lection of bile and p ancreatic secretions in the su bhep atic interval follow ing su rgery. A d ecreased risk of gastric can-
space (Fig. 33.7). If d isconnection of the am p ulla is recog- cer has been observed d u ring the first 15 years after gas-
nized intraop eratively, the d u od enal stum p m ay be m obi- trectom y. Cancer red u ction is likely d u e to the rem oval of
lized fu rther and brought over the am pu lla. The am p u lla or at-risk mu cosa from the d istal stom ach. In contrast,
the ind ivid u al bile and p ancreatic d u cts m ay then be reim - p atients from 15 to 20 years after gastric resection for ulcer
planted . A Rou x-en-Y lim b of jeju nu m m ay also be created d isease have a relative risk for gastric cancer that is three to
for this p u rp ose. When d iscovered postoperatively, inflam - five tim es that of the age-m atched and sex-m atched general
matory changes m ake d uctal reim plantation im p ractical p op u lation (64,65).
and p ancreaticod u od enectom y becom es necessary. The molecular mechanisms that underlie development of
neoplasia in the remnant stomach are unknown. Decreased
Dumping luminal pH, permitting bacterial overgrowth with increased
production of N-nitroso carcinogens, and reflux of bile acids
The term dumping d efines a p ostop erative synd rom e w ith into the stomach have been postulated to promote cancer
both GI and vasom otor com ponents. The cau se of d u m p - d evelopment. The effects of each are unproven. Vagotomy
ing relates to the unregu lated entry of ingested food into d oes not appear to promote cancer development. A Swedish
the p roxim al sm all bow el after vagotom y and either resec- population-based study of 7,198 vagotomized patients fol-
tion or d ivision of the pyloric sphincter (Table 33.7). Early lowed for 9 to 18 years did not reveal increased risk (66).
d u m p ing sym p tom s occur w ithin 1 hou r of a m eal and Prognosis is usually guarded because many gastric remnant
inclu d e nau sea, epigastric d iscom fort, and palp itations. cancers are diagnosed at an ad vanced stage (67,68). Reported
Severely sym p tom atic p atients m ay also have d izziness or 5-year survival ranges from 7% to 33%.
syncop e. Late d u m ping sym ptom s follow a m eal by 1 to
3 hou rs and m ay inclu d e reactive hypoglycem ia.
Althou gh 5% to 10% of patients experience m ild d u m p -
■ GASTRIC CANCER
ing sym p tom s in the early p ostoperative period , m inor In the United States, gastric cancer rem ains am ong the
d ietary alterations and the passage of tim e bring im p rove- top ten cau ses of cancer-related d eaths for both m en and
w om en. Althou gh the incid ence of gastric cancer has hep atic m etastasis. The techniqu e is less sp ecific w ith
d eclined in the United States, approxim ately 22,000 new regard to invasion of ad jacent organs and in assessing for
cases of gastric cancer w ere reported in 2000 (69). p resence of lym p hatic m etastases.
End oscop ic u ltrasou nd is u sefu l to characterize su bep -
ithelial lesions that may be confused w ith gastric cancer.
■ Pathogenesis Ultrasou nd -d irected biopsy of subm ucosal tum ors is possi-
Gastric cancer risk is increased in stom achs that contain ble. End oscop ic u ltrasou nd can assess the d ep th of gastric
polyp s. Risk is related to polyp histology, size, and nu m ber. w all p enetration by gastric cancer and d em onstrates good
H yp erplastic gastric polyps are consid ered to have no neo- correlation w ith intraop erative assessm ent and histologic
plastic p otential. In contrast, ad enomatou s polyps have a find ings. Perigastric lym p h nod es involved w ith tum or are
d efinite risk for d evelopm ent of m alignancy (70). The risk reliably id entified and m ay be biop sied w ith u ltrasou nd
is greatest for polyps 2 cm in d iam eter. Multiple ad eno- gu id ance. Becau se end oscop ic u ltrasou nd has a lim ited
matou s p olyp s fu rther increase the risk of cancer. Althou gh d ep th of tissu e p enetration, hep atic m etastases are not
nitrites in the d iet have been d em onstrated to have a role in d etectable; this lim itation hind ers com p lete p reop erative
gastric carcinogenesis in anim als, specific hum an d ietary staging of gastric cancer p atients.
constituents that prom ote tu m or form ation have not been
id entified . Surgical Therapy
Long-term infestation w ith the organism H. pylori Surgical resection is the only cu rative treatm ent for gastric
app ears to p red isp ose to subsequ ent d evelopm ent of gas- cancer, bu t in the United States ad vanced d isease at the
tric carcinom a. H. pylori is u nequivocally associated w ith tim e of d iagnosis prevents curative resection for m ost
the d evelop ment of chronic gastritis, and regions of the p atients. The su rgical objectives in gastric cancer are to
w orld w ith high rates of gastric ad enocarcinom a also have attem p t cu re in p atients w ith localized tu m or and to pro-
a high p revalence of H. pylori infection. Child hood acqu isi- vid e palliation that is both effective and safe for patients
tion of H. pylori infection ap p ears to be linked to the su bse- w ith ad vanced m alignancy. Op erative treatm ent of gastric
qu ent d evelopm ent of prem alignant lesions and invasive ad enocarcinom a has focu sed on the d etection of m etastatic
cancer. In the United States, seropositivity for H. pylori d isease, the lim its of gastric resection for p otentially cur-
increases the risk for cancer d evelopm ent ap proxim ately able lesions, the extent of p erigastric lym p had enectom y,
threefold , and in Japanese Am erican m ales in H aw aii, the role of sp lenectom y, and the m anagem ent of d irectly
H. pylori-p ositive su bjects d em onstrate a sixfold increase in involved ad jacent organs.
incid ence (71,72). H. pylori infection is associated w ith
d evelop m ent of ad enocarcinom a of both m ajor histologic Laparoscopy
typ es and w ith tu m ors arising in the bod y or antru m of the The ability of cross-sectional im aging to d etect m etastatic
stom ach. H. pylori infection is not a significant risk factor d isease is less sensitive w hen tu m or involves the su rface
for cancers of the gastroesop hageal ju nction; these tu m ors of the liver, th e om en tu m , and th e p eritoneal su rfaces.
are frequ ently associated w ith m u cosal abnorm alities of These are com m on sites for gastric cancer m etastasis that
Barrett esop hagu s. H ow ever, infection w ith H. pylori alone are am enable to lap aroscop ic exam ination. Diagnostic
cannot exp lain the d evelopm ent of gastric cancer. In N orth lap aroscop y can be com bin ed w ith lap aroscop ic u ltra-
Am erica, ap p roxim ately 50% of ad u lts old er than 50 are sou nd . Preop erative end oscop ic u ltrasou nd and lap aro-
serop ositive for H. pylori, yet only a sm all fraction d evelop scop ic u ltrasou nd are com p lim entary techniqu es. When
gastric cancer. combined, a 100% sensitivity in d etecting inoperable tumors
has been rep orted (73).
Detection of incu rable lesions is im p ortant becau se the
■ Diagnosis m ean life exp ectancy of affected p atients is 3 to 9 m onths.
The m ost com m on sym p toms of gastric cancer are not sp e- Most p atients w ith m etastasis can be treated w ithout the
cific and inclu d e p ain, anorexia, and w eight loss. These need for p alliative su rgical resection. In one recent stud y,
sym p tom s resem ble those of a nu m ber of nonneop lastic no p atients d eem ed incu rable by lap aroscop y requ ired
gastrod u od enal d iseases, especially benign peptic u lcer. su bsequ ent op eration (74).
Fiberoptic end oscop y is the d efinitive d iagnostic m ethod
w hen gastric cancer is susp ected , and only gastric biop sy Resection
can d efinitively d ifferentiate benign from m alignant gastric Over the p ast d ecad e the su rgical treatm ent of gastric can-
ulcers. Accu racy of d iagnosis can exceed 95% if m u ltip le cer has d iverged , w ith m inim ally invasive ap p roaches for
biopsy sp ecim ens are obtained . early cancers and increasingly rad ical op erations for
Cross-sectional im aging, m ost com m only CT, has been ad vanced tu m ors. The greatest exp erience w ith early gas-
used to assess extragastric spread . When perform ed w ith tric cancer has been rep orted by Jap anese su rgeons. The
ingestion of oral contrast, CT reliably d em onstrates infiltra- Jap anese Gastric Cancer Association d efines early gastric
tion of the gastric w all by tum or, gastric u lceration, and cancer as a tu m or in w hich invasion is restricted to the
m u cosa or su bm u cosa regard less of the p resence or w ith d ecreased su rvival (86). Patients w ith histologically
absence of lym p h nod e m etastasis (75). For tu m ors con- p ositive m argins of resection are at highest risk to d evelop
fined to the m u cosa, lym p hatic m etastasis is p resent in 1% recu rrent d isease, w ith p ositive m argins strongly corre-
to 3% of cases; w ith su bm u cosal involvem ent the rate of lated w ith d evelop m ent of anastom otic recu rrence. Retro-
nod al p ositivity increases to betw een 14% and 20% sp ective stu d ies su ggest that a 6-cm d istance from the
(76,77). tu m or m ass to the p oint of resection is associated w ith the
End oscop ic m u cosal resection has been rep orted for low est rate of anastom otic recu rrence. Larger m argins
w ell-d ifferen tiated m u cosal tu m ors of 3 cm w ithou t have not im p roved su rvival.
u lceration. Most series have been restricted to w ell- Ad vancements in operative technique and in p ostoper-
d ifferentiated ad enocarcinom as or ad enom as of less than ative p hysiologic su p p ort have im p roved resu lts of m ajor
30 m m size, end oscop ic u ltrasou n d find in gs consistent gastric resection d u ring the p ast three d ecad es. Increas-
w ith an intram u cosal lesion, and absence of u lceration ingly rad ical gastric operations can be perform ed w ith
(78). Throm bocytop enia, the need for anticoagu lation, and accep table m orbid ity and low m ortality. The risk of p ostop-
significant com orbid ities have been contraind ications. The erative m ortality is very clearly related to age, w ith several
end oscop ic techniqu e is enhanced by the su bm u cosal rep orts ind icating a tw ofold to fivefold increase in m ortal-
injection of viscou s com p ou n d s su ch as hyalu ronic acid , ity for p atients old er than 70 (87). Althou gh m ortality risk
glycerol, hyd roxyp rop yl m ethylcellu lose, or fibrinogen is not significantly d ifferent for subtotal gastrectom y and
to elevate the m u cosa. Electrosu rgical knives of variou s total gastrectom y in p atients you nger than 70, for old er
configu rations have been d evelop ed to enable en bloc p atients, total gastrectom y d ou bles mortality. Mortality
resection. rates for total gastrectom y now range from 2% to 7%
Becau se local recu rrence is m ore com m on w ith p iece- (88,89).
m eal resection, rem oval of the tu m or as a single sp ecim en Becau se gastric cancer m etastasizes so frequ ently to
is cru cial. Proced u re tim es are longer and com p lications lym p h nod es, rad ical extirp ation of p erigastric lym p h
su ch as p erforation are m ore com m on if the lesion is nod es has been ad vocated as a therap eu tic m aneu ver (90).
located in the u p p er third of the stom ach, is larger than The therap eu tic benefit of extend ed lym p had enectom y in
20 m m , or exhibits u lceration (79). Bleed ing d u ring resec- the treatm ent of gastric ad enocarcinom a w as d erived ini-
tion is com m on, bu t alm ost alw ays easily controlled end o- tially from retrosp ective exp eriences and rem ains contro-
scop ically. Proton p u m p inhibitor ad m inistration increases versial. The first favorable exp erience w as rep orted by the
safety (80). Exp erience is im p ortant. Proced u re tim es Jap anese Research Society for Gastric Cancer (91,92). In the
im p rove after end oscop ists have p erform ed 30 interven- original Jap anese system , resections w ere characterized as
tions (79). follow s:
In a series of 445 patients, 5% experienced postop era-
R1—resection of stom ach, om entu m , and perigastric lym ph
tive bleed ing or p erforation (81). In 17%, histologic exam i-
nod es;
nation revealed subm ucosal invasion necessitating further
R2—resection of stom ach, om entu m , and en bloc removal
operative treatm ent. Ad d itional analysis, w hich su ggests
of the su p erior leaf of the transverse m esocolon, the p an-
und erd iagnosis of tum or invasion in 45% and m issed lym -
creatic capsule, and lymph nod es along the branches of
phatic m etastasis in 9%, urges continu ed stu d y before
the celiac artery and in the infrad u od enal and suprad u o-
accep tance of this techniqu e (82).
d enal areas;
Lap aroscop ic gastrectom y has also been rep orted for
R3—resection of the above stru ctu res, p lu s lym ph nod es
treatm ent of gastric m alignancy, w ith p u rp orted ad van-
along the aorta and esop hagu s, along w ith the spleen,
tages of red u ced p ain, shorter hosp italization, and
the tail of the p ancreas, and skeletonization of vessels in
im p roved qu ality of life (83). Long-term cancer control
the portahep atis.
rates for lap aroscop ic gastrectom y have not yet been
rep orted by controlled clinical trial. In one series of The cu rrent Jap anese classification system is based on
43 cases of lap aroscop ic gastrectom y, a relatively high anatom ical location of lym p h nod es. Up p er abd om inal
incid ence of p ositive su rgical m argins, local recu rrence, nod es are grou p ed into fou r levels (N 1–N 4) relative to the
and gastric rem nant cancer w ere rep orted (84). In con- location of the p rim ary tu m or. The extent of lym phad enec-
trast, lap aroscop ic gastrectom y for treatm ent of GI stro- tom y corresp ond s to the level of nod al d issection, w ith
m al tu m ors achieved ad equ ate oncologic control in 98% higher levels of d issection involving nod es at greater
of p atients (85). rem ove from the prim ary tu m or.
The extent of gastric resection is d eterm ined by the Only retrosp ective stu d ies of extend ed p erigastric lym -
need to obtain a resection m argin free of m icroscop ic d is- p had enectom y have been rep orted from Jap an. Stage for
ease. Gastric cancer frequ ently d em onstrates intram u ral stage, initial rep orts su ggested an im p rovem ent of 10% for
sp read d u e to the extensive intram u ral cap illary and lym - p atients treated w ith R2 or R3 op erations (91–94). The ben-
p hatic netw ork w ithin the stom ach. Microscop ic involve- efits of extend ed lym p had enectom y have not been con-
m ent of the resection m argin by tu m or cells is associated firm ed in observational stu d ies from centers ou tsid e Japan.
Rand om ized trials have also failed to d em onstrate a sur- m orbid ity (105). Sp lenectom y is not ind icated u nless the
vival ad vantage for extend ed lym p had enectom y w hen tu m or d irectly invad es the sp leen or involves sp lenic hilar
entire p atient p op u lations w ere analyzed (95–99). lym ph nod es.
An effect of extend ed lym p h ad en ectom y that m ay Resection of the tail of the pancreas d oes not im prove
m itigate su rvival ad vantage is the “u p staging” of tu m ors. su rvival. In a large British trial, both m orbid ity and m ortal-
As ad d itional lym p h nod es are rem oved , ad d itional ity w ere d ou bled w hen d istal pancreatectom y w as part of
microm etastatic d isease is d iscovered . Patients are conse- the op eration (98). Similar resu lts have been reported in
qu ently placed in higher stage categories w ith m ore accu- sm aller observational series. Pancreatectom y is ind icated
rate, althou gh w orse, p rognosis (100). Patients w ho d o not only if there is d irect invasion of the d istal p ancreas by the
und ergo extend ed lym p had enectom y have m icrom etas- p rim ary tu m or. Resection of ad jacent organs, m ost com -
tases, w hich are u nd etected and , becau se of progressive m only the d istal p ancreas or transverse colon, m ay be
tu m or grow th and recurrence, w ill d ecrease the survivor- requ ired for local control if d irect invasion is p resent. In
ship of the staging grou p to w hich they are assigned . these p atients, op erative m orbid ity is increased and long-
The safety of extend ed lym p had enectom y is controver- term su rvival ap p roxim ates 25% (106).
sial. Rep orts from a national Japanese registry ind icate a Total gastrectom y is p erform ed alm ost exclu sively in
contem porary m ortality of 1% (101). Sim ilarly, low m or- the context of gastric cancer. This p roced u re is ind icated
tality risks have been rep orted from m u lti-institu tional tri- for gastric tu m ors at the esop hagogastric ju nction, in the
als in Italy and Germ any (100,102). In contrast, rep orts p roxim al stom ach, and along the p roxim al lesser cu rva-
from the United States, Britain, and the N etherland s have tu re. For p atients w ith carcinom a of the gastric card ia,
ind icated increased short-term m orbid ity and in-hosp ital esop hagectom y has no su rvival ad vantage w hen ad d ed to
mortality (96–100). total gastrectom y if tu m or resection can be achieved (107).
H istologically p ositive lym p h nod es m ay be p resent in Moreover, ad d ition of esop hagectom y is associated w ith
the splenic hilu m and along the splenic artery, and sp lenec- significantly higher m orbid ity.
tom y has been rou tinely practiced in som e centers, esp e- The most important complication of total gastrectomy is
cially in Jap an. Sp lenectom y has not been d em onstrated to anastomotic leak at the esop hagojeju nal anastomosis (Fig.
im prove su rvival for sim ilarly staged patients (103,104). 33.8). In tw o rand omized trials, anastomotic failure w as
Sp lenectom y has a clearly ad verse effect on p ostop erative observed in 7% and 11% of patients w ho und erw ent total
morbid ity and m ortality. Septic com plications d ue to p an- gastrectomy (108,109). Anastomotic leak may be herald ed
creatic fistu la and abscess form ation are the m ajor causes of by unexp lained tachycard ia w ithout fever or leukocytosis.
FIGURE 33.8. Creation of a sta-

pled esophagojejunostomy. A: The
proximal jejunum is divided creat-
ing a Roux limb. An opening is made
in the transverse mesocolon to the Middle colic
left of the middle colic vessels. The
vessels
distal end of the transected jejunum
is passed retrocolically to the area Opening in
of the distal esophagus. mesocolon
HRF '04
Ligament of Treitz
A
Anti-
mesenteric
border
'04
HR F
B C
Transverse
mesocolon
defect
50 cm from
esophagojejunal
anastomosis
E '04
D HR F
FIGURE 33.8. (Continued ) B: The jejunal limb is approximated to the esophagus without angulation or tension. The stapled jejunal
closure is excised to allow introduction of an EEA-type stapling device. C: An EEA stapling device is introduced into the opened end of the
Roux-en-Ylimb and positioned along the antimesenteric border of the jejunum. The anvil is reattached. The anvil is inserted into the distal
esophagus, and a previously placed purse string suture is tied. When the EEA device is fired, an end-to-side esophagojejunal anastomo-
sis is created. D: After withdrawal of the EEA stapler, the open end of the jejunal limb is closed with an application of a TA stapler. With the
surgeon’s guidance, a nasogastric tube is placed across the anastomosis. Anastomotic integrity is insured by observing for bubbles in a
saline-filled operative field as the anesthesiologist insufflates air through the nasogastric tube. The jejunum is occluded to permit anasto-
motic distention. E: Intestinal continuity is restored through an end-to-side enteroenterostomy 50 cm distal to the esophagojejunal anas-
tomosis. The mesenteric defect in the transverse mesocolon is approximated to the jejunal limb with interrupted sutures.
A B
FIGURE 33.9. (A) Water-soluble contrast study demonstrating a contained leak at an esophagojejunal anastomosis (arrow).
(B) Anastomosis after healing of leak.
Water-soluble contrast rad iography should be used to con- card iom yopathy, d yslipid emia, pulmonary insufficiency,
firm leakage (110) (Fig. 33.9). Intralum inal suction d ecom- sleep apnea, and several types of cancer (Table 33.8). Socioe-
pression and perianastomotic d rainage m ay be u sed to conomic impairment and psychosocial d isord ers are also
create a controlled fistula w ith expectant fistula closure. increased in morbidly obese individuals. Morbid obesity has
Severe su rrou nd ing inflam m ation usually prohibits d irect an increased risk of premature mortality.
operative repair. Anastomotic d ehiscence contributes sub- Weight loss reduces the risks of obesity-related comor-
stantially to the reported operative mortality of total gas- bidities. For obese patients, w eight reduction by as little as 5%
trectomy (108,109). to 10% of initial weight produces measurable improvements
The performance of total gastrectomy creates a substan- in glucose intolerance, hypertension, and lipid abnormalities.
tial postoperative nutritional challenge. Reconstruction w ith Behavioral interventions and d ietary m od ification are
a variety of small intestinal pouch configurations has been som etim es effective in m od erate obesity. These m easures
reported in observational series (111,112). No controlled data
currently exist to prefer pouch reconstruction to simple Table 3 3 .8 O besit y-r ela t ed h ea lt h seq u ela e
Roux-en-Y esophagojejunostomy.
Hypertension
■ MORBID OBESITY Accelerated atherosclerosis

Hypertrophic cardiomyopathy
Obesity is ep id em ic in the United States. An estim ated 20%
Dyslipidemia
of Am ericans are obese, a proportion that has risen annu -
ally for each of the p ast 10 years. Obesity is a m ajor p u blic Diabetes mellitus
health p roblem in Canad a, Western Europe, and N ew Alveolar hypoventilation
Zealand , and m any nonw estern countries are also rep ort- Sleep apnea
ing an increasing prevalence of obesity.
Hepatic steatosis
Degrees of obesity are qu antified on the basis of bod y
m ass ind ex (BMI), expressed as w eight in kilogram s p er Deep vein thrombosis
(height in m eters)2. An optim al BMI of 20 to 25 kg/ m 2 has Venous stasis ulcers
been d eterm ined actu arially w ith an initial sam p le size of Pulmonary embolism
approxim ately 20,000 ind ivid uals and life table analysis of
Gastroesophageal reflux
4.2 m illion ind ivid u als follow ed for 17 years (113). A BMI
40 kg/ m 2 d efines m orbid obesity. A BMI of 35 kg/ m 2 m ay Hernias
be accep ted as m orbid obesity in the presence of obesity- Degenerative joint disease
related com p lications su ch as d iabetes m ellitu s. Ap p roxi- Female urinary incontinence
m ately 4 m illion Am ericans have a BMI betw een 35 and
Female hirsutism
40 kg/ m 2; another 1.5 m illion have a BMI of 40 kg/ m 2.
Severe obesity is classified as “morbid ” because of the Amenorrhea
strong association w ith secondary obesity-related diseases. Intertriginous dermatitis
Morbid obesity is associated with increased risk of hyperten- Carcinoma of uterus, breast, prostate, and colon
sion, noninsulin-dependent diabetes mellitus, hypertrophic
are ineffective in m orbid obesity, w ith recid ivism rates of 2 years (116). This effect w as p ersisten t. At an 8-year
95% w ithin 1 year. To d ate no p harm acologic agents have follow -u p , the incid ence of d iabetes w as five tim es low er
been d eveloped that are both effective and safe for the in the su rgical grou p relative to u noperated controls.
treatm ent of obesity. In 1991, a N ational Institutes of H ealth Relative to nonobese su bjects, systolic and d iastolic
Consensu s Develop m ent Panel recom m end ed op erative blood p ressu re are increased in obesity. Left ventricu lar
intervention for m orbid ly obese ind ivid uals (BMI of 40 m ass and w all thickness are increased ; ejection fraction
kg/ m 2) on the basis that w eight red u ction by nonsu rgical and d iastolic fu nction are d ecreased in obese su bjects. One
techniqu es w as seld om achieved . The panel also recom - year after su rgery, each of these p aram eters is im proved .
m end ed consid eration of su rgery for less severely obese The greater the w eight loss, the greater the red uction in left
ind ivid u als (BMI of 35 to 40 kg/ m 2) w ith com orbid cond i- ventricular m ass and the greater the im provement in d ias-
tions such as d iabetes m ellitu s or sleep apnea. tolic fu nction.
Postop erative su ccess requ ires carefu l patient selection. Pulm onary fu nction is im proved w ith surgical w eight
In ad d ition to the presence of severe obesity as d efined red u ction. The p ercentage of p atients rep orting p hysical
above, the p atient m ust p rovid e evid ence of failu re to lose inactivity is d ecreased by tw o-third s. Sleep ap nea, present
w eight u nd er m ed ical su p ervision and the m otivation and in 23% of su rgically treated p atients p reop eratively, w as
em otional reserve necessary to und ergo the su rgical proce- observed in 8% after 2 years (117). N o change in frequency
d u re and su bsequ ent lifestyle changes. Com orbid cond i- of sleep ap nea w as observed in the control grou p .
tions shou ld be sought and treated . Psychiatric evaluation Questionnaire d ata suggest that w eight red u ction has
is often u sefu l. beneficial econom ic consequ ences. Workd ays lost to illness
Contem p orary bariatric p roced u res all involve a d egree or d isability are red u ced in years 2 to 5 follow ing su rgery.
of gastric restriction (Fig. 33.10). Roux-en-Y gastric byp ass, Qu ality of life instru m ents record im p rovem ent in p sy-
the m ost com mon proced ure in N orth Am erica, involves chosocial scales. The greater the w eight loss, the greater the
creating a small pou ch of the proxim al stom ach, d rained im provem ent.
via a segm ent of the proxim al jeju nu m . In this p roced u re,
the d istal stom ach and d uod enum are bypassed . Gastric Intraoperative Management
restriction is augm ented by m alabsorption in the biliopan- Sp ecially d esigned op erating tables are requ ired for
creatic d iversion proced u re. The latter proced u re has been bariatric su rgery. Stand ard op erating room tables have a
fu rther m od ified w ith d u od enal sw itch. m axim u m w eight lim it of 200 kg, w hile those d eveloped
The small volume of the gastric reservoir limits oral sp ecifically for bariatric p roced u res are cap able of hold ing
intake, and the major factor causing w eight loss after 450 kg. Becau se m ost bariatric p roced u res requ ire tilting of
bariatric proced ures is red uced caloric ingestion. In gastric the table, efforts m u st be m ad e to assu re that the p atient
bypass, the small outlet from the gastric pouch may also d oes not slip on its su rface. A so-called bean bag, a soft p ad
retard gastric emptying. In each of the illustrated proce- filled w ith thou sand s of sm all p lastic p ellets, is useful for
dures, the dumping synd rome m ay occur, inhibiting inges- this p u rp ose. The bean bag is m old ed to the p atient’s bod y
tion of calorie-dense food s. Biliopancreatic d iversion is and , w ith ap p lication of su ction, firm ly conform s to the
designed to ind uce malabsorption to further augment the p atient’s contou rs.
effects of gastric restriction. Bile and pancreatic secretions d o Pressu re sores and neu ral inju ries are m ore com m on
not mix w ith food until the terminal ileum , limiting the time in obese su rgical p atients, esp ecially d iabetics and the
and mucosal surface area for digestion and absorption. su p er obese. Inju ries to the u lnar nerve and the lateral
A broad exp erience has accu m ulated w ith the su rgical fem oral cu tan eou s nerve are m ost com m on. In m ost
treatment of m orbid obesity. Three rand om ized stu d ies instances, inju ry caused by m alp ositioning or stretch is neu-
and nu m erou s nonrand om ized stud ies have been p u b- rapraxic and reversible. Pad d ed p rotection of p ressu re
lished since 1986 that exam ine the efficacy of gastric areas is cru cial.
byp ass. The rep orts prior to 2000 relate to proced u res p er- Intraop erative blood pressu re m easurem ents w ill be
form ed via lap arotom y. At 24 m onths after operation, a falsely increased if an inap p rop riately sm all blood p res-
m ean of 60% of excess w eight is lost. For m ost p atients, su re cu ff is u sed . The cu ff blad d er shou ld id eally encircle
w eight loss is m axim al betw een 1 and 2 years p ostop era- the entire arm , bu t it m u st be at least of 75% of arm circu m -
tively, w ith a m ean 13-pou nd regain betw een 2 and 5 years ference. Accu rate noninvasive blood p ressu re m easure-
and stability thereafter (114). A recent rep ort of biliop ancre- m ents m ay be obtained from the ankle or w rist. Invasive
atic d iversion d em onstrated average excess w eight loss of arterial m onitoring shou ld be u sed in the su p er obese.
75% (115). Follow -u p ranged from 1 to 21 years. Pneu moperitoneum u sed d uring laparoscopy may
Surgically ind u ced w eight loss is effective in red u cing ad versely affect systemic circu lation in obese patients, and
card iovascu lar risk. At 2 years, su rgically treated p atients use of the Trend elenbu rg position may exacerbate circula-
d em onstrated significant im p rovem ents in hyp ertension, tory changes. Elevated intra-abd ominal pressure increases
d iabetes m ellitu s, hyperinsulinem ia, hypertriglycerid em ia, systemic vascular resistance. For intra-abd ominal pressures
and levels of high-d ensity lipoprotein cholesterol. A 32- 10 mm H g, venou s return to the right heart increases d ue
fold red u ction in d iabetic risk factors w as observed at to d ecreased splanchnic blood pooling. As intra-abd ominal
Proximal gastric pouch
Bypassed stomach
50 cm
'04
F
HR
100 cm
FIGURE 33.10. A: Configuration of Roux-en-Y gastric bypass. In this

configuration the stomach is divided. The Roux limb is anastomosed
along the lesser curvature. B: Biliopancreatic diversion. This operation
consists of dividing the small bowel 250 cm proximal to the ileocecal
valve. A proximal segment of divided small intestine is anastomosed to
the distal limb 50 cm proximal to the ileocecal valve. The distal small
bowel is anastomosed to the stomach as a Roux limb. Digestion occurs in
the common limb of intestine. C: Biliopancreatic diversion modified by
'04 duodenal switch. The stomach is resected, producing early satiety but
HRF
leaving a normal pylorus. The first portion of the duodenum is divided. The
jejunum is divided 250 cm proximal to the ileocecal valve, and the distal
end at this point of division is anastomosed to the proximal segment of
duodenum. The remaining duodenum and proximal small bowel are anas-
C tomosed to the ileum 100 cm proximal to the ileocecal valve.
pressu re increases to 20 m m H g, inferior vena caval is more d ifficu lt in m orbid ly obese p atients. Tachycard ia,
com p ression d ecreases venou s retu rn and consequ ently w orsening abd om inal or back p ain, and hiccups m ay be
d im inishes card iac ou tp u t. Renal blood flow d ecreases the only signs. Concern m and ates rad iologic investigation
w hen intra-abd om inal p ressu re exceed s 20 m m H g, and w ith a w ater-solu ble contrast agent. If a leak is confirm ed
glom eru lar filtration rate d rop s. H yp ovolem ia accentu - that com m u nicates freely w ith the p eritoneal cavity, the
ates these changes at higher intra-abd om inal p ressu res. d efect shou ld be closed if feasible and the u p p er abd om en
Both obesity and pneumoperitoneum ad versely affect res- shou ld be externally d rained . A gastrostom y tu be should
piratory mechanics. be p laced in the d istal, exclu d ed stom ach. In selected cases
of leak in w hich the extravasation is contained , conserva-
Postoperative Complications tive, nonop erative m anagem ent can be su ccessfu l (123).
The largest nu m ber of rep orted exp eriences w ith bariatric Acu te gastric d istension of the byp assed d istal stom ach
surgery relate to op erations p erform ed by laparotom y. Col- m ay occu r after either op en or lap aroscop ic gastric byp ass.
lectively, these rep orts illustrate that for Rou x-en-Y gastric Acute d istention m ay be a resu lt of postoperative peritoni-
byp ass, 30-d ay m ortality ranges from 0.3% to 2% (118). tis or as a m echanical consequ ence of an obstru cted
Overall com p lication rates range from 20% to 40%. The enteroenterostom y. Continu ou s abd om inal pain, d isten-
most frequent acute postoperative com plications includ e sion, and hiccu p s are frequ ently associated signs. Plain
d eep vein throm bosis (DVT), pulm onary em bolism , anas- abd om inal x-rays or CT d em onstrate m assive gastric
tom otic leakage, and w ou nd infection. Late com p lications d ilatation, often w ith an air-flu id level. Acu te gastric d is-
inclu d e stom al stenosis, staple line d ehiscence, and m ar- tention m u st be treated em ergently becau se of the p otential
ginal u lceration. Micronutrient d eficiencies have also been for ischem ic necrosis of the stom ach. Percu taneou s or oper-
rep orted long-term . ative gastrostom y d ecom p ression is therap eu tic.
Lap aroscop ic gastric byp ass is associated w ith a p ost-
operative m ortality rate of 0% to 1.7%, similar to the rate Incisional Hernia
observed w hen the op eration is p erform ed via lap arotomy Postoperative incisional hernias are a m ajor problem in
(117). Contem p orary reports of laparoscopic Rou x-en-Y op en bariatric su rgery, occu rring in ap p roxim ately 20% of
gastric bypass d em onstrate very low m ortality rates and cases. A p rior incisional hernia d ou bles this risk. Port site
progressive d eclines in postoperative comp lications (118). incisional hernias have been rep orted in 0% to 0.5% of
Lap aroscop ic bariatric su rgery requ ires ad vanced laparo- p atients after lap aroscop ic gastric byp ass, rep resenting the
scop ic skills, and m any observers have com m ented u p on clearest ad vantage of the lap aroscop ic ap p roach (117).
an extend ed “learning cu rve” not accou nted for by cu rrent
mortality statistics. The range of p ostoperative com p lica- Cholelithiasis
tions record ed w ith op en gastric byp ass has also been Rap id w eight loss, by either d ietary m eans or follow ing
noted for proced ures perform ed laparoscopically. su rgery, is associated w ith an increased risk of cholelithia-
sis. H alf of p atients follow ing bariatric su rgery w ill
Deep Venous Thrombosis d em onstrate gall blad d er slu d ge; one-third w ill d evelop
Overall, the most common cause of death postoperatively is sym p tom atic gallstones. The u se of p rop hylactic ursod iol
pulmonary embolism. DVT occurs in approximately 2% of for 6 m onths follow ing gastric byp ass red u ced the inci-
patients treated via open operation or laparoscopically (119). d ence of sym p tom atic gallstones to 2% (124). Many su r-
Immobility, venous stasis, and the effects of pneumoperi- geons have u sed the high incid ence of p ostop erative
toneum may contribute to thrombus formation. Physical cholelithiasis to ju stify p rop hylactic cholecystectom y at the
examination is not diagnostically reliable. Doppler examina- tim e of gastric byp ass. N o controlled trial exists to su pport
tion is the preferred initial diagnostic test. Controlled trials or refu te this p ractice.
are not available establishing a standard of care for DVT pro-
phylaxis in bariatric surgery. Sequential compression stock- Stomal Complications
ings and injection of either subcutaneous heparin or The gastrojeju nal anastom osis that d rains the p roxim al
low-molecular w eight heparin are recommended. The conse- gastric p ou ch in gastric byp ass is in tentionally sm all at
quences of pulmonary embolism are more severe in bariatric 1 cm . Larger stom as d o not create enou gh restriction
patients relative to the general population. The hypoventila- of food p assage an d are not associated w ith ad equ ate
tion syndrome and cor pulmonale are increased in obese w eigh t loss. As a con sequ en ce, stom al sten osis is rela-
patients. Both d iminish functional cardiac reserve. tively com m on , occu rrin g in 12% of cases (125). Affected
p atients d evelop early satiety, recu rrent vom iting, and
Anastomotic Dehiscence u p p er abd om in al p ain . Thiam ine d eficiency has been
Anastom otic d ehiscence or su ture line leak has been linked to p ersistent vom iting, w ith d istu rbances in vision
reported in 1.2% of patients und ergoing open gastric bypass and gait (126,127). Stom al stenosis m ay also cau se sym p -
(120). This complication occurs in 3% to 6% of cases per- tom s of gastroesop hageal reflu x.
formed laparoscopically but d iminishes w ith surgeon expe- Upper end oscopy is the preferred means of investiga-
rience (121,122). The d iagnosis of postoperative p eritonitis tion; contrast rad iographs are not demonstrative of the
degree of stenosis. Most patients w ith gastrojejunal stenosis 14. Branicki FJ, Boey J, Fok PJ, et al. Bleed ing d u od enal u lcer⎯a p rosp ec-
tive evalu ation of risk factors for rebleed ing and d eath. Ann Surg
after gastric bypass will respond to endoscopic dilatation. 1990;211:411–418.
Stom al u lceration m ay also cau se stom al stenosis. The 15. Mueller X, Rothenbu ehler J, Am ery A, et al. Factors p red isp osing to
rate of gastrojeju nal stom al u lcer approxim ates 10%. The fu rther hem orrhage and m ortality after p ep tic u lcer bleed ing. J Am
Coll Surg 1994;179:457–461.
etiology of stom al u lceration is often m ultifactorial, inclu d - 16. Branicki FJ, Colem an SY, Folk PJ, et al. Bleed ing p ep tic u lcer: a
ing acid secretion by parietal cells in the p roxim al pou ch, p rospective evalu ation of risk factors for rebleed ing and m ortality.
ischem ia of the jeju nal lim b, and N SAID u se. Failure to heal World J Surg 1990;14:262–270.
17. Larson G, Schm id t T, Gott J, et al. Up p er gastrointestinal bleed ing:
w ith p roton p u m p inhibitors and elim ination of N SAIDs p red ictors of ou tcom e. Surgery 1986;100:765–772.
su ggests jeju nal ischem ia; m u cosal biop sies are confirm a- 18. Im hof M, Schrod ers C, Ohm ann C, et al. Im p act of early op eration on
tory. Prolonged u lceration cau ses m echanical obstru ction the m ortality from bleed ing peptic ulcer⎯ten years’ exp erience. Dig
Surg 1998;15:308–314.
becau se of chronic cicatrization. 19. Feld m an RA, Eccersley AJ, H ard ie JM. Ep id em iology of Helicobacter
Stap le line d isru p tion is a com p lication of gastric pylori: acqu isition, transm ission, p op u lation p revalence and d isease-
bypass techniqu es in w hich the stom ach is not d ivid ed . to-infection ratio. Br Med Bull 1998;54:39–53.
20. Vaira D, Menegatti M, Miglioli M. What is the role of Helicobacter
This com p lication is su ggested by recu rrent w eight gain pylori in com plicated p eptic ulcer d isease? Gastroenterology 1997;113:
after w eight loss stabilization. Correction requires reop era- S78–S84.
tion to restap le and d ivid e the stom ach. Stap le line d isru p - 21. Boey J, Choi SKY, Alagaratnam TT, et al. Risk stratification for p erfo-
rated d u od enal u lcers: a prospective valid ation of p red ictive factors.
tion occu rs in 1% of patients. Ann Surg 1987;205:22–28.
N u trient d eficiencies are anticip ated after Roux-en-Y 22. Sanabria AE, Morales CH , Villegas MI. Lap aroscop ic rep air of p erfo-
gastric bypass becau se the d istal stom ach and d uod enum rated p eptic ulcer d isease. Cochrane Database Syst Rev 2005;(4):
CD004778.
are byp assed . Defective absorption of vitam in B12, folate, 23. El-Om ar EM, Penm an ID, Ard ill JE, et al. Helicobacter pylori infection
iron, and calciu m are su fficiently com m on to w arrant rou - and abnorm alities of acid secretion in patients w ith d uod enal u lcer
tine postop erative su pplem entation. Biliopancreatic d iver- d isease. Gastroenterology 1995;109:681–691.
24. Aalykke C, Lau ritsen JM, H allas J, et al. Helicobacter pylori and risk of
sion w orsens m icronu trient d eficiencies becau se of the u lcer bleed ing am ong u sers of nonsteroid al anti-inflam m atory d ru gs:
more severe anatomic rearrangement. Steatorrhea is univer- a case-control stud y. Gastroenterology 1999;116:1305–1309.
sal and high d ose calcium supplementation and monthly 25. H ay JA, Lyu bashevsky E, Elashoff J, et al. Up p er gastrointestinal hem -
orrhage clinical gu id eline⎯d eterm ining the op tim al hosp ital length
intram u scu lar vitam in D are required to prevent m etabolic of stay. Am J Med 1996;100:313–322.
bone d isease. Protein m alnutrition is the m ost severe com - 26. Jiranek GC, Kozarek RA. A cost-effective ap p roach to the p atient w ith
plication of biliop ancreatic d iversion. p ep tic u lcer bleed ing. Surg Clin North Am 1996;76:83–103.
27. Collins R, Langm an M. Treatm ent w ith histam ine H 2 antagonists in
acu te up p er gastrointestinal hem orrhage: im plications of rand om ized
trials. N Engl J Med 1985;313:660–666.
■ REFERENCES 28. Khu roo MS, Yattoo GN , Javid G, et al. A com p arison of om ep razole
an d p lacebo for bleed in g p ep tic u lcer. N Engl J Med 1997;336:
1. Am erican Cancer Society. Cancer facts and figu res. Available at: 1054–1058.
w w w.cancer.org. 29. Peterson WL, Cook DJ. Antisecretory therap y for bleed ing p ep tic
2. Terry MB, Gaud et MM, Gam m on MD. The ep id em iology of gastric u lcer. JAMA 1998;280:877–878.
cancer. Semin Radiat Oncol 2002;12:111–127. 30. Lau JYW, Su ng JJY, Lee KKC, et al. Effect of intravenou s om ep razole
3. Martin RC II, Jaqu es DP, Brennan MF, et al. Extend ed local resection on recu rrent bleed ing after end oscop ic treatm ent of bleed ing p ep tic
for ad vanced gastric cancer: increased survival versus increased m or- u lcers. N Engl J Med 2000;343:310–316.
bid ity. Ann Surg 2002;236:159–165. 31. Coop er GS, Ch ak A, Way LE, et al. Early end oscop y in u p p er
4. Schw arz RE, Zagala-N evarez K. Gastrectom y circu m stances that gastrointestin al hem orrhage: association s w ith recu rren t bleed in g,
influence early postop erative ou tcom e. Hepatogastroenterology 2002;49: su rgery, and length of hosp ital stay. Gastrointest Endosc 1999;49:
1742–1746. 145–152.
5. Wainess RM, Dim ick JB, Up chu rch GR, et al. Ep id em iology of surgi- 32. Laine L, Cohen H , Brod head J, et al. Prosp ective evalu ation of im m e-
cally treated gastric cancer in the United States, 1988–2000. J Gastroin- d iate versu s d elayed refeed ing and p rognostic valu e of end oscop y in
test Surg 2003;7:879–883. p atients w ith u pp er gastrointestinal hem orrhage. Gastroenterology
6. St Peter SD, H olcom b GW III, Calkins CM, et al. Op en versu s lap aro- 1992;102:314–316.
scop ic pylorom yotom y for p yloric stenosis: a p rosp ective, rand om - 33. Lin H J, Wang K, Perng CL, et al. N atu ral history of bleed ing p ep tic
ized trial. Ann Surg 2006;244:363–370. u lcers w ith a tightly ad herent clot: a p rosp ective observation.
7. Yagm u rlu A, Barn h art DC, Vern on A, et al. Com p arison of th e in ci- Gastrointest Endosc 1996;43:470–473.
d ence of com p lications in op en and lap aroscop ic p ylorom yotom y: 34. Cook DJ, Guyatt GH , Salena BJ, et al. End oscop ic therap y for acu te
a con cu rren t sin gle in stitu tion series. J Pediatr Surg 2004;39: nonvariceal u p p er gastrointestinal hem orrhage: a m eta-analysis.
292–296. Gastroenterology 1992;102:139–148.
8. Alain JL, Grousseau D, Terrier G. Extram u cosal p ylorom yotom y by 35. Ku bba AK, Palm er KR. Role of end oscop ic injection therap y in the
lap aroscop y. Surg Endosc 1991;5:174–175. treatm ent of bleed ing p eptic u lcer. Br J Surg 1996;83:461–468.
9. H all N J, Van Der Zee J, Tan H L, et al. Meta-analysis of lap aroscopic 36. Lau JY, Su ng JJ, Lam Y, et al. End oscop ic retreatm ent com p ared w ith
versu s open p ylorom yotom y. Ann Surg 2004;240:774–778. su rgery in p atients w ith recu rrent bleed ing after initial end oscop ic
10. H aricharan RN , Ap raham ian CJ, Celik A, et al. Lap aroscop ic control of bleed ing ulcers. N Engl J Med 1999;340:751–756.
p ylorom yotom y: effect of resid ent training on com p lications. J Pediatr 37. H su P, Lai K, Lin X, et al. When to d ischarge p atients w ith bleed ing
Surg 2008;43:97–101. pep tic u lcers: a p rospective stu d y of resid u al risk of rebleed ing.
11. Laine L, Peterson WL. Bleed ing p ep tic u lcer. N Engl J Med 1994;331: Gastrointest Endosc 1996;44:382–387.
717–727. 38. Bru llet E, Cam p o R, Calvet X, et al. Factors related to the failu re of
12. Silverstein FE, Gilbert DA, Ted esco FJ, et al. The national ASGE sur- end oscop ic injection therapy for bleed ing gastric u lcer. Gut 1996;39:
vey on u pper gastrointestinal bleed ing. Gastrointest Endosc 1981;27: 155–158.
73–79. 39. Poxon VA, Keighley MRB, Dykes PW, et al. Com p arison of m inim al
13. Gilbert DA. Epid em iology of u p p er gastrointestinal bleed ing. Gas- and conventional su rgery in patients w ith bleed ing peptic ulcer: a
trointest Endosc 1990;36(Su p p l 5):8–13. m ulticentre trial. Br J Surg 1991;78:1344–1345.
40. Millat B, H ay JM, Valleu r P, et al. Em ergen cy su rgical treatm ent 67. H olstein C. Long-term p rognosis after p artial gastrectom y for gastro-
for bleed ing d u od en al u lcer: oversew in g p lu s vagotom y versu s d u od enal u lcer. World J Surg 2000;24:307–314.
gastric resection, a controlled rand om ized trial. World J Surg 1993;17: 68. Safatle-Riberio AV, Riberio U, Reynold s JC. Gastric stu m p cancer:
568–574. w hat is the risk? Dig Dis 1998;16:159–168.
41. Mulholland MW, Debas H T. Chronic d u od enal and gastric u lcer. Surg 69. Boring CC, Squires TS, Tong T. Cancer Statistics 1993. CA Cancer J Clin
Clin North Am 1987;67:489–507. 1993;43:19.
42. Johnston D, Blackett RL. Recu rrent p ep tic u lcers. World J Surg 1987;11: 70. H arju E. Gastric polyp osis and m alignancy. Br J Surg 1986;73:532–533.
274–282. 71. Parsonnet J, Fried m an GD, Vand ersteen DP, et al. Helicobacter pylori
43. Millat B, Fingerhu t A, Borie F. Su rgical treatm ent of com p licated d u o- infection and the risk of gastric carcinom a. N Engl J Med 1991;325:
d enal ulcers: controlled trials. World J Surg 2000;24:299–306. 1127–1131.
44. Graham DY, White RH , Moreland LW, et al. Du od enal and gastric 72. N om u ra A, Stem m erm ann GN , Chyou P-H , et al. Helicobacter pylori
ulcer prevention w ith m isop rostol in arthritis p atients taking infection and gastric carcinom a am ong Japanese Am ericans in
N SAIDs. Ann Intern Med 1993;119:257–262. H aw aii. N Engl J Med 1991;325:1132–1136.
45. Silverstein FE, Graham DY, Senior JR, et al. Misop rostol red uces seri- 73. Mortensen MB, Scheel-H incke JD, Mad sen MR, et al. Com bined
ous gastrointestinal com p lications in p atients w ith rheu m atoid arthri- end oscopy ultrasonography and lap aroscopic u ltrasonography in the
tis receiving nonsteroid al anti-inflam m atory d rugs: a rand om ized , pretherap eutic assessm ent of resectability in p atients w ith u p p er gas-
d ouble-blind , placebo-controlled trial. Ann Intern Med 1995;123: trointestinal m alignancies. Scand J Gastroenteral 1996;31:1115–1119.
241–249. 74. Bu rke EC, Karp eh MS Jr, Conlou KC. Lap aroscop y in the m anage-
46. Rokkas T, Karam eris A, Mavrogeorgis A, et al. Erad ication of m ent of gastric ad enocarcinom a. Ann Surg 1997;225:262–267.
Helicobacter pylori red uces the possibility of rebleed ing in p eptic ulcer 75. Ad achi Y, Shiraishi N , Kitano S. Mod ern treatm ent of early gastric
d isease. Gastrointest Endosc 1995;41:1–4. cancer: review of the Jap anese exp erience. Dig Surg 2002;19:333–339.
47. Jasp ersen D, Koerner T, Schorr W, et al. Helicobacter pylori erad ication 76. N akam u ra K, Morisaki T, Su gitani A, et al. An early gastric carcinom a
red uces the rate of rebleed ing in u lcer hem orrhage. Gastrointest Endosc treatm ent strategy based on analysis of lym p h nod e m etastasis.
1995;41:5–7. Cancer 1999;85:1500–1505.
48. Santand er C, Gravalos RG, Ced enilla AG, et al. Maintenance treat- 77. Ku nisaki C, Shim ad a H , Takahaski M, et al. Prognostic factors in early
m ent vs Helicobacter pylori erad ication in preventing re-bleed ing of gastric cancer. Hepatogastroenterology 2001;48:294–298.
the peptic u lcer d isease: a clinical trial and follow u p for tw o years. 78. Lee S-H , Park J-H , Park DH , et al. Clinical efficacy of EMR w ith su b-
Gastroenterology 1995;108:A208. m u cosal injection of a fibrinogen m ixture: a prospective rand om ized
49. Maier M, Sohilling D, Dorlars D, et al. Erad ication of H elicobacter trial. Gastointest Endosc 2006;64:691–696.
pylori or H 2 blocker m aintenance therap y after p ep tic u lcer bleed ing: 79. Im agaw a A, Okad a H , Kaw ahara Y, et al. End oscop ic su bm u cosal d is-
a p rosp ective rand om ized trial. Gastroenterology 1995;108:A156. section for early gastric cancer: resu lts and d egrees of technical d iffi-
50. Crofts TJ, Park KGM, Steele RJC, et al. A rand om ized trial of nonop ercu lty as w ell as su ccess. Endoscopy 2006;38:987–990.
ative treatm ent for p erforated p ep tic u lcer. N Engl J Med 1989;320:970. 80. Watanabe Y, Kato N, Maehata t, et al. Safer end oscopic gastric m ucosal
51. Boey J, Wong J, Ong GB. A p rosp ective stu d y of op erative risk factors resection: p rosp ective proton p um p inhibitor ad m inistration. J Gas-
in perforated d u od enal u lcers. Ann Surg 1982;195:265. troent Hepatol 2006;21:1675–1680.
52. Ku jath P, Schw and ner O, Bru ch H -P. Morbid ity and m ortality of per- 81. Ono H , Kond o H , Gotod a T, et al. End oscop ic m u cosal resection of
forated pep tic gastrod u od enal u lcer follow ing em ergency surgery. treatm ent of early gastric cancer. Gut 2001;48:225–229.
Langenbecks Arch Surg 2002;387:298–302. 82. Korenaga D, Orita H , Mackaw a S, et al. Pathological ap p earance of
53. Lau WY, Leung KL, Kw ong KH , et al. A rand om ized stu d y com paring the stom ach after end oscopic m u cosal resection for early gastric can-
laparoscopic versus open repair of perforated peptic u lcer using cer. Br J Surg 1997;84:1563–1566.
su ture or su tu reless techniqu e. Ann Surg 1996;224:131. 83. Cu schieri A. Laparoscop ic gastric resection. Surg Clin North Am 2000;
54. Lau WY, Leung KL, Zhu XL, et al. Lap aroscop ic rep air of p erforated 80(4):1269–1284.
p ep tic u lcer. Br J Surg 1995;82:814. 84. N okaki I, Ku bo Y, Kurita A, et al. Long-term ou tcom e after lap aro-
55. Lu nevicius R, Morkeviciu s M. System atic review com p aring laparoscopic w ed ge resection for early gastric cancer. Surg Endosc 2008;22:
scopic and op en rep air for p erforated p ep tic u lcer. Br J Surg 2005;92: 2665–2669.
1195–1207. 85. Sexton JA, Pierce RA, H alp in VJ, et al. Lap aroscop ic gastric resection
56. Boey J, Lee NW, Koo J, et al. Im m ed iate d efinitive su rgery for p erfo- for gastrointestinal strom al tu m ors. Surg Endosc 2008;22:2583–2587.
rated d uod enal u lcers: a p rosp ective controlled trial. Ann Surg 1982; 86. Wanebo H J, Kenned y BJ, Chm iel J, et al. Cancer of the stom ach: a
196:338. patient care stu d y by the Am erican College of Su rgeons. Ann Surg
57. Ren P, H u ang J, Shin J, et al. Jeju nojeju nogastric intu ssu scep tion: a 1993;218:583–592.
rare intu ssu scep tion in an ad u lt p atient after gastric su rgery. Gastroin- 87. Kranenbarg EK, van d e Veld e CJH . Gastric cancer in the eld erly. Eur J
test Endosc 2002;56(2):296–298. Surg Oncol 1998;24:384–390.
58. Eckhau ser FE, Conrad M, Knol J, et al. Safety and long-term d u rabil- 88. Bittner R, Bu tters M, Ulrich M, et al. Total gastrectom y: u p d ated op er-
ity of com pletion gastrectom y in 81 p atients w ith p ostsurgical gastro- ative m ortality and long-term su rvival w ith particular reference to
p aresis synd rom e. Am Surgeon 1998;64:1–7. patients old er than 70 years of age. Ann Surg 1996;224:37–42.
59. McCallu m RW, Polp alle SC, Schirm er B. Com p letion gastrectom y for 89. Schw arz R, Karp eh MS, Brennan MF. Factors p red icting hosp italiza-
refractory gastroparesis follow ing su rgery for peptic ulcer d isease, tion after operative treatm ent for gastric carcinom a in patients old er
long-term follow -u p w ith su bjective and objective p aram eters. Dig than 70 years. J Am Coll Surg 1997;184:9–15.
Dis Sci 1991;36(11):1556–1561. 90. Shiu MH , Moore E, Sand ers M, et al. Influ ence of the extent of resec-
60. Cohen AM, Ottinger LW. Delayed gastric em p tying follow ing gastrec- tion on survival after curative treatm ent of gastric cancer: a retrospec-
tom y. Ann Surg 1976;184(6):689–696. tive m u ltivariate analysis. Arch Surg 1987;122:1347–1351.
61. Zarzour JG, Christein JD, Drelichm an ER, et al. Percu taneou s tran- 91. Maru yam a K, Okabayashi K, Kinoshita T. Progress in gastric cancer in
shepatic d u od enal d iversion for the m anagem ent of d u od enal fistu - Japan and its lim it of rad icality. World J Surg 1987;11:418–425.
las. J Gastrointest Surg 2008;12:1103–1109. 92. N ogu ch i Y, Im ad a T, Matsu m oto A, et al. Rad ical su rgery for gas-
62. Rod key GV. Safe m anagem ent of the im p ossible d u od enu m , risk tric can cer: a review of th e Jap an ese exp erien ce. Cancer 1989;64:
avoid ance in su rgery of p ep tic u lcer. Arch Surg 1988;123:558–562. 2053–2062.
63. Eld h J, Kew enter J, Kock N G, et al. Long-term resu lts of su rgical 93. Ad achi Y, Kam aku ra T, Mori M, et al. Role of lym p h nod e d issection
treatm ent for d u m p ing after p artial gastrectom y. Br J Surg 1974;61: and sp lenectom y in node-positive gastric carcinom a. Surgery 1994;116:
90–93. 837–841.
64. H ansson L. Risk of stom ach cancer in p atients w ith p ep tic ulcer d is- 94. Baba H , Maehara Y, Takeu chi H , et al. Effect of lym p h nod e d issection
ease. World J Surg 2000;24:315–320. on the prognosis in patients w ith nod e-negative early gastric cancer.
65. Tersm ette AC, Giard iello FM, Tytgat GN J, et al. Carcinogenesis after Surgery 1994;117:165–169.
rem ote p ep tic u lcer su rgery: the long-term p rognosis of p artial gas- 95. Maeta M, Yam ashiro H , Saito S, et al. A p rosp ective p lot stu d y of
trectom y. Gastroenterology 1991;101:148–153. extend ed (D3) and su p erextend ed p ara-aortic lym p had enectom y
66. Lu nd egård h G, Ekbom A, McLau ghlin JK, et al. Gastric cancer risk (D4) in patients w ith T3 or T4 gastric cancer m anaged by total gastrec-
after vagotom y. Gut 1994;35:946. tom y. Surgery 1999;125:325–331.
96. Robertson CS, Chung SCS, Wood s SDS, et al. A p rosp ective rand om - 112. Espat N J, Karp eh M. Reconstru ction follow ing total gastrectom y: a
ized trial com p aring R1 su btotal gastrectom y w ith R3 total gastrec- review and su m m ary of the rand om ized p rosp ective clinical trials.
tom y for antral cancer. Ann Surg 1994;220:176–182. Surg Oncol 1999;7:65–69.
97. Bonekam p JJ, H erm ans J, van d e Veld e CJH . Extend ed lym ph-nod e 113. Deitel M. Surgery for m orbid obesity: a review. Eur J Gastroenterol
d issection for gastric cancer. N Engl J Med 1999;340:908–914. Hepatol 1999;11(2):57–61.
98. Cushieri A, Fayers P, Field ing J, et al. Postop erative m orbid ity and 114. Pories WJ, Sw anson MS, MacDonald KG, et al. Who w ou ld have
m ortality after D1 and D2 resections for gastric cancer. Lancet 1996; thou ght it? An op eration p roves to be the m ost effective therap y for
347:995–999. ad u lt-onset d iabetes m ellitu s. Ann Surg 1995;222:339–352.
99. Siew ert JR, Bottcher K, Stein H J, et al. Relevant p rognostic factors in 115. Scopinaro N , Ad am i GF, Marinari GM, et al. Biliop ancreatic d iversion.
gastric cancer: ten-year resu lts of the Germ an gastric cancer stu d y. World J Surg 1998;22:936–946.
Ann Surg 1998;228:449–461. 116. Sjöström L. Surgical intervention as a strategy for treatm ent of obesity.
100. Kod era Y, Yam am ura Y, Shim izu Y, et al. The nu m ber of m etastatic Endocrinology 2000;13(2):213–320.
lym ph nod es: a p rom ising prognostic d eterm inant for gastric carci- 117. Schau er PR, Ikram u d d in S. Lap aroscop ic su rgery for m orbid obesity.
nom a in the latest ed ition of the TN M classification. J Am Coll Surg Obes Surg 2001;81(5):1145–1179.
1998;187:579–603. 118. Maher JW, H aw ver LM, Pucci A, et al. Fou r hu nd red fifty consecu tive
101. Lee JS, Douglass H O. D2 d issection for gastric cancer. Surg Oncol laparoscopic Roux-en-y gastric bypasses w ith no m ortality and
1997;6(4):215–225. d eclining leak rates and lengths of stay in a bariatric training p ro-
102. Pacelli F, Doglietto GB, Bellantone R, et al. Extensive versu s lim ited gram . J Am Coll Surg 2008;206:940–944.
lym ph nod e d issection for gastric cancer: a com p arative stu d y of 320 119. Byrne TK. Com plications of su rgery for obesity. Obes Surg 2001;81(5):
p atients. Br J Surg 1993;80:1153–1156. 1181–1193.
103. Stip a S, DiGiorgio A, Ferri M, et al. Resu lts of cu rative gastrectom y for 120. Su rgerm an H J. Gastric su rgery for m orbid obesity. In: Zinner MJ, ed .
carcinom a. J Am Coll Surg 1994;179:567–572. Maingot abdominal operations, 10th ed . Stam ford CT: Ap p leton &
104. Otsuji E, Yam agu chi T, Saw ai K, et al. End resu lts of sim u ltaneou s Lange; 1997.
sp lenectom y in p atients u nd ergoing total gastrectom y for gastric can- 121. Wittgrove AC, Clark GW. Lap aroscop ic gastric byp ass, Rou x-en-Y-500
cer. Surgery 1996;120:40–44. patients: techniqu e and resu lts w ith 3–6 m onth follow u p . Obes Surg
105. Weitz J, Jaques DP, Brennan M, et al. Association of sp lenectom y w ith 2000;10:233–239.
p ostoperative com plications in p atients w ith p roxim al gastric and 122. Lee S, Carm od y B, Wolfe L, et al. Effect of location and sp eed of d iag-
gastroesophageal junction cancer. Ann Surg Oncol 2004;11:682–689. nosis on anastom otic leak ou tcom e in 3828 gastric byp ass cases. J Gas-
106. Shchep otin IB, Chorny VA, N au ta RJ, et al. Extend ed su rgical resec- trointest Surg 2007;11:708–713.
tion in T4 gastric cancer. Am J Surg 1998;175:123–126. 123. Csend es A, Bu rd iles P, Bu rgos AM, et al. Conservative m anagem ent of
107. Stein H J, Feith M, Siew ert JR. Cancer of the esop hagogastric junction. anastom otic leaks after 557 op en gastric byp asses. Obes Surg 2005;15:
Surg Oncol 2000;9:35–41. 1252–1256.
108. Bonenkam p JJ, Songu n I, H erm ans J, et al. Rand om ized com p arison of 124. Sugerman HJ, Brewer WH, Shiffman ML, et al. A multicenter, placebo-
m orbid ity after D1 and D2 d issection for gastric cancer in 996 Dutch controlled, randomized, double-blinded, prospective trial of prophy-
p atients. Lancet 1995;345:745–748. lactic ursodiol for the prevention of gallstone formation follow ing
109. Rod er JD, Böttchen K, Siew ert JR, et al. Prognostic factors in gastric gastric-bypass induced rapid w eight loss. Am J Surg 1995;169:91–97.
carcinom a: resu lts of the Germ an gastric carcinom a stu d y 1992. Cancer 125. Sanayal AJ, Su germ an H J, Kellu m JM, et al. Stom al com p lications of
1993;72:2089–2097. gastric bypass: incid ence and ou tcom e of therap y. Am J Gastroenterol
110. Hogan BA, Winter D, Broe D, et al. Prospective trial com paring contrast 1992;87:1165–1169.
swallow, computed tomography and end oscopy t id entify anastomotic 126. Kram er LD, Locke GE. Wernicke’s encep halop athy: com p lication of
leak follow ing oesophageal surgery. Surg Endosc 2008;22:767–771. gastric p lication. J Clin Gastroenterol 1987;9:549–552.
111. N akane Y, Okum ura S, Akehira K, et al. Jeju nal p ou ch reconstru ction 127. Mason ME, Jalagani H , Vinik AI, Metabolic com p lications of bariatric
after total gastrectom y for cancer: a rand om ized controlled trial. Ann su rgery: d iagnosis and m anagem ent issu es. Gastroenterol Clin N Am
Surg 1995;222(1):27–35. 2005;34:25–33.
CHAPTER
34
Complications of Hepatic Surgery

Theodore H. Welling and J ames A. Knol
Over the p ast 30 years, ad vances in preoperative evalu a- Selection of p atients for hep atic resection requ ires
tion, anesthetic m anagem ent, su rgical techniqu e, and p ost- appropriate rad iologic workup or staging to eliminate
op erative care have allow ed for exp and ing ind ications for patients for whom cure or significant palliation is not possi-
perform ance of m ajor and m inor liver resections for a vari- ble. Multiphase (arterial, portal venous, and hepatic venous)
ety of su rgical d iseases affecting the liver (Table 34.1). Su r- com p u ted tom ograp hy (CT), or m agnetic resonance im ag-
gical therapy m ay be an ad junct or the prim ary therap y, ing (MRI), is requ isite in d eterm ining the extent of tu m or in
d ep end ing on the d isease. The m ortality associated w ith the liver, relationship s to the vascu latu re of the liver, and
hep atic su rgery or resection has d eclined from abou t 30% w hether a resection to rem ove the tu m or w ill sp are ad e-
in p ast years to less than 1% to 4% at high volu m e institu - qu ate parenchym a (resid u al liver rem nant) to allow p ost-
tions, d ep end ing on the com plexity of the proced u re and op erative su rvival. This typ e of im aging also allow s for
concom itant liver d isease (1). H ow ever, know led ge regard - op tim al d etection of d isease and assistance in the d ifferen-
ing the p otential comp lications is im p ortant, becau se tial d iagnosis of liver m asses. In general, if a liver tu m or
hep atic su rgery and resection continu e to be associated ap p ears resectable, biop sy shou ld be avoid ed , u nless the
w ith abou t a 40% m orbid ity rate (2). H epatic su rgical com - biop sy w ill change the d ecision abou t w hether to operate.
plications encom pass a w id e spectrum (Table 34.2). Com - Biop sy risks d issem ination of tu m or w ithin the need le tract
plications sp ecific to the liver relate to the liver ’s high or to the p eritoneal su rfaces.
blood flow, glu cose hom eostasis and protein anabolism , The p atient’s overall health and the extent of com orbid
synthesis of clotting factors, clearance and d eactivation of d isease are significant factors p red icting overall com p lica-
toxins, synthesis and d rainage of bile, and role in p rotec- tions follow ing hep atic su rgery. In a recent large series the
tion from infectiou s agents entering the portal circulation rate of p u lm onary com p lications w as 21% and the rate of
through the gastrointestinal (GI) tract. card iovascu lar com p lications w as 10% (1). Morbid ity and
m ortality for right hep atic lobectom y have been show n to
correlate strongly w ith p reop erative APACH E II scores (3),
■ PATIENT SELECTION
as has the Am erican Society of Anesthesiologists (ASA)
Know led ge of hep atic su rgical com p lications d em and s Classification score (4), emp hasizing the need for app ropri-
that there be ap p rop riate p reop erative evalu ation to bal- ate op tim ization of p atient health and selection.
ance the risks of these com p lications and m ortality against The liver ’s health is the final m ajor d eterm inant in
p otential benefits. In Western cou ntries m ost liver resec- selection of p atients for liver su rgery. Cirrhosis increases
tions are p erform ed for m etastatic colorectal cancer, w ith the m ortality associated w ith any op eration and anesthe-
abou t 20% p erform ed for p rim ary hep atobiliary cancer sia, and an op eration that d ecreases the am ou nt of resid ual
and 10% for benign d isease (1). The ind ications for op era- fu nctioning liver fu rther increases that risk (5). The p res-
tions for these variou s d iseases w ill not be covered here, ence of cirrhosis can raise the m ortality rate follow ing
bu t they d o p lay a role in a d iscu ssion of su rgical com p li- hep atic resection to as high as 4.7%, w hereas the m ortality
cations. If su rgical therapy d oes not appear ju stified , other rate follow ing hep atic lobectom y in the absence of liver d is-
therap ies su ch as ablative strategies, chem oem bolization, ease is 2.6% or less (6). Signs of severe cirrhosis inclu d e
rad iation, or chem otherapy m ay offer significant therap eu - jau nd ice, ascites, and m alnu trition, w ith laboratory corre-
tic ad vantage or the p ossibility of d ow nstaging d isease lates including bilirubin above 2 mg/ dL, serum albumin less
such that a safer operation is possible. The ind ications for than 3 g/ d L, and a platelet count less than 100,000 per L.
op eration m u st be ap p rop riate to ju stify any op eration CT or MRI m ay show a relatively sm all liver w ith notching
w ith associated com p lications and p ossible m ortality. of the su rface and , often, relative atrop hy of the right lobe
and hyp ertrop hy of the left lateral segment and caud ate
Theodore H. Welling*, James A.** Knol: Sections of Trans- lobe. A p relim inary d iscrim inator is the Child – Pugh score;
p lantation* and General Su rgery**, Dep artm ent of Surgery, all p atients w ith grad e C and m ost w ith grad e B are not
University of Michigan H ealth System consid ered satisfactory cand id ates for op eration. The
415
Table 3 4 .1 Su r gica l d isea ses of t h e liver Table 3 4 .3 In t ra h ep a t ic liver volu m e ra t ios

Neoplasm—benign Hepatic adenoma
ba sed on CT sca n for n or m a l liver s
Focal nodular hyperplasia, symptomatic Segments Percent of Total Liver Volume
Hemangioma, symptomatic
Biliary cystadenoma Right liver 65 7 (49–82)
Hemangioendothelioma Left liver 33 7 (17–49)
Neoplasm—malignant Hepatocellular carcinoma Segment IV 17 4 (10–29)
Intrahepatic cholangiocarcinoma Bisegment II III 16 4 (5–27)
Hilar cholangiocarcinoma
Gallbladder cancer Segment I 2 0 (1–3)
Hepatoblastoma
Hemangioendothelioma Adapted from Abdalla EK, Denys A, Chevalier P, et al. Total and segmental liver
volume variations: implications for liver surgery. Surgery2004;135:414–420.
Direct invasion by adjacent cancers—stomach,
colon, renal, adrenal, vena caval
Metastases—colorectal and highly selected:
neuroendocrine, melanoma, gastrointestinal or d ep ressed p latelet cou nt, p red icts p ersistent hepatic
stromal tumor, endometrial, breast, stomach d ecom p ensation in over 75% of p atients p ostresection (7).
Biliary disease Intrahepatic or high extrahepatic bile duct A variety of other m ethod s have been p rop osed to p red ict
stricture w hich p atients w ith liver d isease are cand id ates for resec-
Intrahepatic bile duct stones tion and how m u ch of the d iseased liver m ay safely be
Intrahepatic bile duct cysts (Caroli disease) rem oved or ablated (8–10). Severe fibrosis, jau nd ice d u e to
Biliary fistula cau ses other than cirrhosis, steatosis greater than 30%, and
Infection Pyogenic abscess a history of chem otherap y, p articu larly hep atic artery infu -
Echinococcal abscess sion therap y, are other ind icators of a d amaged liver and
Amebic abscess increase the risk of resection or ablation (11,12).
Vascular disease Hepatic artery aneurysm or pseudoaneurysm Preservation of rem aining liver health follow ing liver
Biliary-arterial or biliary-venous fistula resection is of p aram ou nt im p ortance. Resection p lanning
Arterial-portal fistula or arterial-hepatic requ ires estim ation of the p ostresection fu nctioning liver
venous fistula rem nant. Postop erative liver d ysfu nction is significantly
increased in p atients w ith norm al liver function w hen the
liver rem nant is less than 25% of the initial liver volum e
Mod el for End -stage Liver Disease (MELD) score has been (13). In the norm al liver there is variation in the p rop ortions
show n to be m ore p red ictive of w orse outcom es, w ith of the hep atic segm ents that com p rise the u su al anatom ic
patients w ith scores of greater than or equal to 9 experienc- liver resections (Table 34.3) (14). The exp erienced liver sur-
ing as high as 29% p erioperative m ortality, d epend ing on geon can m ake som e estim ates on the basis of the im aging
extent of resection (4). The p resence of portal hypertension, stu d ies. H ow ever, volu m etric analysis shou ld be d one in
as d iagnosed by elevated hepatic vein pressu re grad ient p atients w ith a norm al liver in w hom an extend ed lobec-
tom y is p lanned or in p atients w ith d am aged livers in
w hom any resection or ablation equ ivalent or greater than
a single liver segm ent is anticip ated (15). In ad d ition, in
Table 3 4 .2 Com p lica t ion s of liver su r ger y
p atients for w hom there is a p ossibility of p reexisting liver
Liver Surgery d amage, biop sy from the area of the p otential rem nant liver
Intraoperative hemorrhage Postoperative hemorrhage shou ld be consid ered in ord er to confirm the p resence or
Intrahepatic hematoma Postoperative coagulopathy absence of liver d isease.
Liver failure Perihepatic abscess For p atients in w h om resection or ablation can not be
Biliary fistula Biliary stricture execu ted becau se of the threat of sm all fu nctioning liver
Biloma Bile peritonitis rem nant, ind u cing hyp ertrop hy in the liver that is to be
Cholangitis Hepatic abscess p reserved m ay be attem p ted . H yp ertrop h y is m ost often
Wound infection Pneumonia
ind u ced by p ercu taneou s p ortal vein em bolization to the
Hemobilia Hepatic necrosis
liver that is to be resected , w ith op eration follow ing at 4
Hepatic artery thrombosis Portal vein thrombosis/insufficiency
Intraoperative air embolus Hepatic vein thrombosis/insufficiency to 6 w eeks follow ing em bolization (16,17). Patients in
Ascites Peritonitis w h om p reop erative p ortal vein em bolization shou ld be
Gastrointestinal bleeding Pleural effusion consid ered are listed in Table 34.4. H igh d ose focal liver
irrad iation also ind u ces hyp ertrop hy in the u nirrad iated
Special to Ablation Procedures
Myoglobinuria Thermal injury to surrounding liver. Op erative p ortal vein ligation w ill also cau se
structures hyp ertrop h y in th e op p osite liver lobe bu t w ith m ore
complications relative to percutaneous embolization. Finally,
Chapter 34 • Complications of Hepatic Surgery 417
Table 3 4 .4 In d ica t ion s for p r eop era t ive p or t a l bleed ing control. Rem oval of d evitalized liver tissu e and
vein em boliza t ion p rovision of ad equ ate d rainage for bile d u ct d isru ption are
the other m ajor im p eratives in the m anagem ent of trau -
Patients with underlying normal liver m atic liver inju ries.
Future liver remnant volume less than 30% Op eration for bleed ing after a p ercu taneou s biop sy
Major hepatectomy associated with gastrointestinal procedure shou ld be ind ivid u alized , based on the ind ications for the
Resection of bilobar tumors, including a major hepatectomy biop sy. Bleed ing from liver tissu e at the site of need le entry
Patients with diseased liver can alm ost alw ays be stop p ed w ith p ressu re, com bined
Cirrhosis w ith fu lgu ration, or w ith horizontal m attress sutu re of the
Severe fibrosis need le entrance site at the liver cap su le. If the bleed ing is
Jaundice com ing from a hem angiom a at the liver ’s su rface, w here
Steatosis greater than 30% the need le p u nctu red the tu m or, bleed ing m ay be stopped
Chemotherapy
w ith p ressu re or w ith a gently p laced horizontal m attress
From Clavien PA, Emond J, Vauthey JN, et al. Protection of the liver during hepatic su tu re arou nd the need le entrance site, bu t it m ay occasion-
surgery. J Gastrointest Surg 2004;8:313–327. ally requ ire resection of the tu m or by enu cleation. Bleed ing
from other tu m ors can u su ally be stop p ed w ith p ressu re,
cau tery (at high settings), argon p lasm a coagulation, or
planned two-stage hepatectomy for tumor has been reported su tu re, and rarely requ ires resection. H ow ever, d ep end ing
as a m eans of resecting all tu m ors, and avoid s a sm all fu ncon the su rgeon’s exp erience, resection m ay be the preferred
tioning rem nant liver (18). rou te. In som e cases arterial bleed ing from w ithin the liver
m ay not read ily stop w ith p ressu re and can resu lt in intra-
■ COMPLICATIONS OF HEPATIC SURGERY hep atic hem atom a. Packing, closing the abd om en, and
em ergent angiography w ith em bolization are the preferred
The com p lications of hep atic su rgery can be variou sly cate- step s in su ch a case.
gorized . For the su rgeon they are m ost u sefu lly d ivid ed Frequ ently, a tu m or that ru p tu res into the peritoneal
into intraop erative and postoperative com plications. cavity or prod u ces intracapsular hem atom a w ill stop
bleed ing sp ontaneou sly, and op eration can be d one on an
u rgent rather than em ergent basis. A history of p rolonged
■ Intraoperative complications oral contracep tive u se in a w om an is a strong p red ictor of
Intraop erative com p lications can be lethal d u ring hep atic hep atic ad enom a, w hereas a history of hep atitis B or C or
surgery or in the early, interm ed iate, or late postop erative cirrhosis ind icates that hepatocellular cancer is likely to be
period s. Decisions m ad e before and d u ring the op eration the cau se of bleed ing. Abnorm al laboratory stu d ies, inclu d -
and the cond u ct of the operation are significant factors in ing hep atitis serologies, liver fu nction stu d ies, and alpha-
the incid ence and severity of intraop erative and p ostop era- fetop rotein su ggest cirrhosis and hep atocellu lar cancer. If
tive com p lications. The m ajor com plications occurring d u r- the situ ation allow s, liver im aging shou ld be d one to d elin-
ing op eration are bleed ing, vascu lar inju ry, air em bolu s, eate the tu m or cau sing the bleed ing. CT or MRI shou ld be
and biliary inju ry. d one w ith contrast, inclu d ing arterial p hase im aging.
Tu m ors that ru p tu re are u su ally hyp ervascu lar and are best
Preexisting Bleeding d emonstrated by arterial phase imaging. N oncontrast scans
Preexisting bleeding associated w ith hepatic surgery is gen- and contrast scans in the p ortal venou s p hase are likely to
erally from blunt or penetrating injury or from rupture of a be confu sing if there is intrahep atic or su bcap su lar hemor-
tumor. Rupture of a benign tumor resulting in bleeding is rhage, w ith d ifficu lty d istingu ishing betw een tum or and
almost exclusively due to hepatic adenoma, with only intrahep atic hem atom a. Becau se the tu m or ’s pathology is
extremely rare case reports of rupture of hepatic heman- not likely to be fu lly certain at op eration, the operative
giomas, spontaneously or associated with blunt trauma, or ap p roach shou ld be that for a m alignant tu m or, w ith p ref-
from focal nodular hyperplasia. Rupture of malignant tumor erence to form al resection as opposed to enu cleation.
with bleeding is almost always due to hepatocellular carci-
noma. Bleeding from liver metastases is vanishingly rare. Intraoperative Bleeding
The p rincip les and m ethod s for d ealing w ith hep atic Intraop erative bleed ing w ith liver op erations, as w ith all
bleed ing from traum a are not this chap ter ’s top ic. The op erations, shou ld be kep t to a m inim u m , and a nu m ber
app roach is based on classification of the inju ry and is of m easu res can be em p loyed to facilitate m inim izing
aim ed at control of bleed ing. Initial m aneu vers are fou r: (a) blood loss. The extent of blood transfu sion has been corre-
packing of the liver w ith p ressu re, (b) achieving card iovas- lated w ith p ostop erative m orbid ity and m ortality in liver
cu lar resu scitation w ith fluid and blood prod u cts, (c) m ain- su rgery (19). Increasing level of blood transfu sion has
taining bod y tem p erature, and (d ) norm alizing coagu lation also been inversely correlated w ith tu m or-free su rvival
as m u ch as p ossible. Control of bleed ing p roceed s from less after liver resection for m alignancy (19–21), w ith a recent
to m ore invasive, perform ing the m inim u m to achieve stu d y on hep atocellu lar carcinom a p atients d em onstrating
Table 3 4 .5 Sou r ces of ext ra h ep a t ic blood loss The clam p s are rem oved sequ entially as the op ening is
closed w ith su tu re.
Liver capsule transgression
Diaphragm injury Portal Hypertension
Hepatic vein injury Som e liver operations m ust be perform ed in the presence
of p ortal hyp ertension. The critical areas to be ad d ressed to
Vena caval injury
m inim ize blood loss are the abd om inal w all, intra-abd om i-
Phrenic vein injury nal ad hesions of the om entu m , the liver hilu m , the gastro-
Variceal injury hep atic ligam ent, and the retrop eritoneu m inferior to the
Right adrenal vein injury liver hilu m . Ad hesions of om entu m to the abd om inal w all
and to the area of the liver hilu m are com m on rou tes of por-
Right adrenal gland injury
tosystem ic d ecom pression and are likely to contain large,
Portal vein injury relatively d elicate vessels w ith blood at pressu re above the
Hepatic artery injury norm al sp lanchnic venou s p ressu re. These ad hesions
shou ld be taken d ow n carefu lly. Large variceal vessels are
often p resent in the gastrohep atic ligam ent, w hich shou ld
increased intraoperative blood loss as an ind epend ent risk also be taken d ow n betw een clam p s or heat coagulation
factor for tum or recu rrence and d isease specific su rvival sealing, rem em bering to evalu ate for the p resence of a
(22). Blood loss that occu rs before transecting the liver can rep laced left hep atic artery crossing the ligam ent. Large
be insid iou sly large—som etim es the m ajor sou rce of blood collaterals m ay be fou nd in the retrop eritoneu m ad jacent or
loss for the op eration. Some of this blood loss is u nd er the anterior to the infrahep atic vena cava, w ith the feed ing ves-
surgeon’s control, bu t som e perihepatic blood loss can be sels occasionally com ing from the liver hilu m . Particularly
d u e to d isease factors. w hen portal hypertension is associated w ith p ortal vein
throm bosis, there w ill be large fragile collateral vessels in
Technical Factors the hep atod u od enal ligament. Attachm ents betw een the
Technical factors leading to perihepatic blood loss in liver d iap hragm and the liver are m u ch less likely to have collat-
surgery are listed in Table 34.5. Experience, know led ge of the erals as a m anifestation of p ortosystem ic shu nting.
anatomy, and a commitment to limited blood loss are impor-
tant to minimize loss from these sources. Achieving as m uch Reoperative Surgery
exposure or visualization as possible, w ith an appropriately Reop erative liver su rgery is u su ally associated w ith
large incision, appropriate retraction, and visualization if increased p erihep atic blood loss becau se of the d en sity of
done laparoscopically, is also important for minimizing liver ad h esions to the d iap hragm , retrop eriton eu m , an d
blood loss in this stage of the liver op eration. Exp osu re righ t ad renal glan d . There is d ifficu lty staying ou t of the
m ay be particularly difficult in the deep-chested patient, in liver and ou t of th e d iap hragm an d ad renal gland w h en
patients w hose liver lies superior to the costal margin, in attem p ting to d issect those stru ctu res from each other.
patients w ith large tumors, and in patients with large livers. Ju d iciou s u se of the cau tery and good exp osu re can m in-
The u su al sou rces of m assive intraop erative bleed ing im ize blood loss. Sp ecial care shou ld be exercised w hen
an d , occasionally, p ostop erative bleed ing are the hep atic ap p roaching the liver hilu m and the regions of the vena
veins and the vena cava. Inju ries occu r at m argins of the cava and the term ini of the hep atic veins.
liver at the m obilization stage or at the m argins of or
w ithin the liver d u rin g tran section of th e liver. Bleed ing Hepatic Bleeding
from these vessels d u rin g th e m obilization stage is Transection of liver tissu e can be associated w ith significant
alm ost alw ays techn ical and avoid able, excep t in th e blood loss. Mortality from intraop erative bleed ing contin-
reop erative setting, w here there m ay be d ense scarring u es to be rep orted , bu t rarely, althou gh blood loss w ith
ad jacent to the m ajor vessels, m aking the d issection and m ajor resections often requ ires one to three transfu sions
control extrem ely d ifficu lt. Althou gh these veins are rela- either intraop eratively or p ostop eratively. In recent series
tively tou gh, avoid ance of excessive traction or torsion on transfu sion ou tliers continue to be ten u nits of blood loss or
the venou s stru ctu res is necessary to avoid tearing. Su tu re m ore (5,19).
ligatu re, su tu re closu re, or vascu lar stap le closu re of Control of minor bleeding points on the raw liver surface
m ed iu m and large tribu taries of the cava are m ore secu re is best addressed with pressure or cautery during liver tran-
than clip s and stand ard ligatu res, w hich have a tend ency section. Major bleed ing points are best controlled w ith suture
to bru sh or roll off d u ring m anip u lations of the liver and technique. Where there is a side opening in a vessel, such as
w ith traction on the vena cava. If a tear d evelop s in the w here a branch has been avulsed, it is preferable to directly
vena cava, or a clam p slip s off a large tribu tary after its close the opening in the vessel with fine suture rather than to
d ivision, finger occlu sion and then serial p lacem ent of include the entire vessel in a mass suture ligature. An end-
Babcock or Alice clam p s on the vessel across the op ening bleeding vessel that has retracted into the liver parenchyma
can u su ally bring a large op ening u nd er qu ick control. can be controlled w ith a figure-8 or horizontal mattress
Table 3 4 .6 Fa ct or s in blood loss d u r in g inflow m u st be recognized , p articu larly in a replaced or

liver t r a n sect ion accessory left hep atic artery crossing the gastrohep atic liga-
m ent. Becau se blood loss from the hep atic veins and their
Unsatisfactory exposure tribu taries w ill still occu r w ith inflow occlu sion, m aintain-
High central venous pressure ing a relatively low central venou s pressure w ill help in
lim iting blood loss d u ring transection (24,25).
Large tumor
Partial vascu lar exclu sion can be perform ed on a part of
Large liver the liver and can very effectively lim it blood loss, as long as
Close proximity of tumor to large intrahepatic vessels d issection rem ains w ithin the exclu d ed p ortion. This
Coagulopathy m ethod is p articu larly ap p licable in the liver w ith cirrhosis
or in other cond itions in w hich the fu nctioning resid u al
Inexperienced surgeon
liver is sm all or com prom ised and w hen the ad d ed insult
Inexperienced surgical assistants of w arm ischem ia cou ld be hazard ou s. For selective inflow
Improper equipment occlu sion, facility w ith intraop erative u ltrasound is essen-
Inappropriate operative approach tial for id entifying the ap p rop riate p ed icle to be occlu d ed
and the p osition of that p ed icle.
Blood loss d u ring liver transection can be nearly com -
p letely elim inated by total vascu lar exclu sion, com prising
suture into the surrounding parenchyma, tied only tight com plete inflow and outflow vascu lar occlu sion of the
enough to occlude the vessel. Control of the cut liver ed ge liver. The blood that is lost is only that w ithin vessels in the
with large mattress sutures is also a helpful w ay to control liver. Total vascu lar exclu sion is accom p lished by (a) estab-
bleeding in situations w here those sutures will not occlude lishing inflow occlu sion, rem em bering that accessory
important blood inflow, bile d rainage, or hepatic venous hep atic arteries m ay be p resent, (b) occlu d ing the infrahep-
drainage of the liver remnant and where the sutures are atic vena cava, and (c) occlu d ing the su p rahepatic vena
placed relatively close to the liver edge. A similar effect can be cava. A m ethod that exclu d es the right ad renal vein and
achieved using a stapler to divide the liver parenchyma lum bar veins requires m obilizing the right lobe of the liver,
where the liver thickness will accommodate its use (3 cm in establishing a w ind ow posterior to the su prahepatic vena
normal liver). Because liver bleeding is frequently from low - cava, d ivid ing p eritoneal attachm ents betw een the cau d ate
pressure vessels, control of bleed ing w ith packing is com- lobe and the left aspect of the vena cava to m obilize the
monly used for brief periods during an operation, but cau d ate lobe anteriorly, and then p lacing an infrahepatic
packing can be prolonged for up to 72 hours and can be very clam p w ith its tip in the w ind ow behind the suprahep atic
useful in the case of an unstable patient or a patient with vena cava. A m ajor consid eration w ith total hep atic vas-
coagulopathy. Hemostatic agents, such as crystallized colla- cu lar exclu sion is that card iac venou s retu rn m ay be com -
gen or coagulating liquids or sprays, cautery at high settings, p rom ised , resu lting in hyp otension w hen total vascular
and the argon plasma coagulator are all useful method s for exclu sion is im p lem ented . H yp otension can usually be
dealing with diffuse bleeding from the raw liver surface. avoid ed if the cen tral venou s p ressu re is raised to abou t
Sewing omentum or peritoneum over the raw surface has not 12 mm H g prior to placing the vena cava clamps. An ad van-
proven effective in stopping bleed ing (23). tage of this method is that resection or d issection in the liver
Factors that are associated w ith large op erative blood arou nd the junction of the major hepatic veins can be more
loss are listed in Table 34.6. As m any of these factors as p os- safely performed ; injuries to those veins can be repaired in a
sible shou ld be controlled to m inim ize bleed ing. Control of relatively blood less field . Disad vantages inclu d e the need
blood loss w hile transecting the liver can u su ally be to push up the central venous pressure, the more extensive
achieved to a rem arkable extent. This control involves both d issection that must be d one to place the clamps, and the
liver blood flow control and the u se of transection m ethod s possibility that a greater w arm ischemic inju ry m ay occu r to
that im p rove exp osu re of vessels. the resid u al liver segm ent than w ou ld occu r w ith inflow
occlu sion alone (26).
Liver Blood Flow Control to Minimize Blood Loss
Inflow occlu sion is the p rim ary m ethod by w hich blood Liver Transection Methods to Minimize Blood Loss
flow control is achieved . There are a variety of m ethod s of Early liver su rgery m ad e u se of the finger-fractu re tech-
perform ing inflow occlu sion. General inflow occlu sion is n iqu e, in w h ich the liver p arenchym a w as cru shed
exem p lified by the Pringle m aneuver, w hich clam p s the betw een th e fingers, leaving behin d the m ore fibrou s ves-
hep atod u od enal ligam ent at the foram en of Winslow. More sels and bile d u cts for control by ligatu re, clip s, stap les,
selective m eans inclu d e occlu sion of p ortal flow to a p artic- or h eat coagu lation -sealin g. Fin ger-fractu re, alth ou gh
ular p ortal segm ent u sing u ltrasound -guid ed placem ent of still occasionally u sefu l, and the m ost rap id w ay of tran-
a balloon catheter or d issecting and occlu d ing by ligatu re secting liver short of sharp transection, tend s to tear the
or stap ling the p ortal triad to only the particu lar p ortion of h ep atic ven ou s stru ctu res becau se th ey con tain less con-
the liver to be resected . The potential for accessory arterial n ective tissu e in th e w all. The techn iqu e m ay tear the
sm aller vascu lar and biliary stru ctu res before they can be agents are p reventative measu res. Treatment for the bleed -
controlled and is less effective in livers that have d evel- ing includ es packing, correction of coagulop athy, procoagu-
op ed fibrosis. lation agents, and ju d iciou s su ture p lacem ent.
Several method s are commonly in use to transect liver in The other source of intraoperative bleed ing after cryoab-
a w ay that p ermits encou ntered nonparenchymal stru ctures lation is through the cryoprobe tract after the probe is with-
to be controlled . The clamp-crush technique uses an instru- d raw n. Two measures prevent bleed ing through this tract.
ment, usually w ith multiple small teeth—such as a vascular The first, and most important, is to avoid placing the initial
clamp—to cru sh the parenchyma in small bites. The need le and guid ew ire for the d ilator and sheath through, or
crushed parenchyma is subsequently aspirated aw ay, and in close proximity to, large vessels. The second is to slid e the
the exposed vascular and biliary structures are ligated . The sheath back into the tract over the probe before w ithd raw ing
Cavitron ultrasonic aspirator (CUSA) technique uses high- the probe, then to w ithd raw the probe, and then to pack the
energy ultrasound transm itted to a su ction tip throu gh a tract w ith small particles of Gelfoam w hile grad ually w ith-
special hand piece. H yd rod issection uses a fine high-pres- d raw ing the sheath. However, rad iofrequency ablation
sure w ater jet to d isrupt the parenchyma. With the CUSA (RFA) is currently the more accepted ablative strategy for
and hyd rod issection, the d isru pted parenchyma is immed i- appropriately selected tumors and avoid s the occasional
ately aspirated throu gh the hand piece, exposing the more bleeding associated with the cryotherapy ablative technique.
fibrous vessels and bile d ucts. These latter tw o techniqu es
are less efficient in fibrotic and cirrhotic livers. Recently, Vascular Injuries
w ith the d evelopment of techniques for laparoscopic liver A normal liver can su rvive permanent interru ption of arte-
resection, high frequency sonic scalpel, bipolar technology, rial inflow if there is normal flow through the portal vein
and linear cu tting staplers have show n applicability in and there is no ad d itional hepatocellu lar inju ry d ue to asso-
selected circumstances (27). In ad d ition, precoagulation ciated prolonged w arm ischemia or d ecreased splanchnic
d evices have proven to be effective by application to the line blood flow secondary to hypotension or due to the use of
of liver d ivision before formal hepatic transection (28,29). vasopressors. If the attachments of the liver to the diaphragm
These mod ern techniques are much more effective in m ain- and the retroperitoneu m remain intact, collateral arterial
taining a blood less field d uring liver transection compared flow has been d emonstrated w ithin 24 hours of ligation of
to finger-fracture w ith no apparent increase in biliary com- the m ain arterial inflow. In over 85% of instances, either the
plications. With a blood less field and exposu re of stru ctures, right or the left hepatic artery can be ligated and there w ill
these method s permit recognition of the internal liver be establishm ent of intrahep atic arterial collaterals to the
anatomy d uring transection, lead ing to less chance of mis- d earterialized sid e im m ed iately or w ithin d ays (30).
d irection d uring liver transection. A norm al liver can also u su ally w ithstand p ortal vein
Map p ing of the p osition of the m ajor vessels w ithin the interru p tion if arterial flow rem ains intact and there is no
liver by intraoperative ultrasound can significantly affect hypotension, d ecreased splanchnic arterial blood flow, or
blood loss associated w ith liver transection. Major resec- hepatocellu lar injury from w arm ischemia. H ow ever, occlu-
tions ap p roach the central or right hepatic veins, w hich, sion of both arterial and venou s blood su p p lies lead s to
becau se they are not generally occlud ed d u ring liver tran- rap id hep atic necrosis and acu te liver failu re. A d iseased
section, can be a m ajor sou rce of blood loss if injured . Main- liver m ay not tolerate d ecreased blood flow from interru p -
taining a centim eter or tw o d istance from these vessels, tion of either portal or hep atic arterial sou rces.
w hen p ossible, avoid s avu lsion of sm all and m ed iu m -sized Intraoperative com plete liver d evascu larization is a
tribu taries, w hich tend s to occu r w hen the d issection is car- technical issu e. Care in d issection in the subhepatic area,
ried im m ed iately ad jacent to these large veins. continual evaluation of orientation w hen d issecting in the
area of the liver hilu m, and id entification of the principal
Cryoablation arteries by palpation for pu lses in the hep atod u od enal liga-
Tw o sources of intraoperative bleed ing that are not comment w ill help prevent hilar vascular injuries. The princi-
mon to other liver operations occur w ith cryoablation. The p les of d issecting the arteries from “large and know n to the
major source of blood loss as a complication of liver cryoab- sm aller and nonpalpable” and from anterior inferior left to
lation is cracking of the liver p arenchym a at the m argins of sup erior and right w ill also help to p revent inju ry to arterial
the ice-ball as it thaw s. Intraparenchymal bleed ing ad jacent stru ctures. Use of intraop erative ultrasound in the hilu m
to the thaw ed ice-ball is not a common problem. If the ice- can help d efine the location of the portal vein in the d ifficult
ball is at the surface of the liver, d u ring the freezing phase, hilum. The portal vein, in ad d ition, has a very consistent
because w ater exp and s as it freezes, the cap su le or su rface p osterior position in the hepatod uod enal ligament, unlike
w ill often fracture. When the ice-ball thaw s, there is a risk of the arteries, w hich are variable in position and cou rse.
bleed ing at these fractu res. The liver can also be avulsed If d ivision of the portal vein or arterial supp ly, or both, in
from the ice-ball if care is not taken, resulting in vessel tears. the hepatoduodenal ligament is discovered intraoperatively,
Care in hand ling the frozen and postfrozen portion of the salvage requ ires im m ed iate revascu larization. For the sur-
liver, observation u ntil the surface has thaw ed before clos- geon inexperienced in vascular reconstruction, assistance of
ing the abd om en, and the u se of su rface- coating hem ostatic a liver transplant su rgeon or vascu lar su rgeon should be
im m ed iately enlisted . The portal vein shou ld be repaired are usually more difficult to dissect individ ually at that level.
first, because the portal vein is the greater source of blood There is some variation in the branching pattern, such that in
flow to the hep atocytes (60% to 70%) than the artery. End - a small percentage of cases there is a tributary from the right
to-end repair can often be d one, particularly if the d uod e- liver draining into the left main duct. Less frequently there
nu m is kocherized , but vein graft may be required . Internal may be a tributary from the left liver d raining into the right
jugular vein, external iliac vein, left renal vein, saphenous d uct (32). Ligation or injury to the remaining bile ducts after
vein, or pericard ial patch can be used as either cond uit or a major resection may not always be apparent, so that great
patch material d ep end ing on the situation. Externally su p- care should be exercised in id entifying and d issecting the
ported polytetrafluoroethylene (PTFE) graft has been u sed bile ducts at the hilum. With lobectomy or trisegmentectomy,
bu t is not the first choice. Repair or anastomosis is u su ally if there is distance betw een tumor and the hilum it is safer to
performed w ith a ru nning fine polypropylene monofila- dissect the bile ducts in a Glissonian fashion—that is, to dis-
ment suture. Arterial repair should be performed w ith a sect into the liver substance slightly aw ay from the liver
spatulated repair using fine polypropylene suture. hilu m ou tsid e the Glisson cap su le an d to d ivid e the p ar-
Reversed saphenous vein can be used for graft if necessary. ticu lar d u ct som ew hat aw ay from the actu al m ain bile
Ad d itional m obility of the proxim al artery can be obtained d u ct bifu rcation (33). Even if the vessels are d ivid ed at
in som e cases by d ivid ing the gastrod u od enal artery. Id e- the hilu m , d ivision of the bile d u ct can be d elayed u ntil
ally, the patient should be heparinized for the repair and the liver p arenchym a is d ivid ed at the hilu m , w hen the
started on aspirin postoperatively. branching pattern can be d emonstrated as the parenchyma
Inju ry of the Glisson sheath-encased p ortal trinity is dissected aw ay. This approach is also useful in dissection
w ithin the liver can occu r. Inju ry at this level is d ifficu lt to for hilar cholangiocarcinoma, w here later d ivision of the bile
treat becau se there is often com bined inju ry to the p ortal d uct may allow for more margin on the tumor.
vein, the accomp anying artery, and the accom panying bile Operative injury to intrahepatic bile d ucts occurs almost
d u ct. The best cou rse is u su ally to su ture repair or ligate the exclu sively w hen operation is carried out w ith d isregard for
injured vessels and observe briefly to d eterm ine how m uch the liver ’s internal anatomy. H ow ever, resections involving
liver is affected , leaving the bile d uct initially u nrep aired . If the hilus (central liver resections and caud ate resections) are
a large am ou nt of liver appears d evascu larized , fu rther noted to be at higher risk of biliary com plications such as
attem p ts shou ld be m ad e to rep air the vessels, esp ecially leaks, raising the incid ence from less than 4% to as high as
the p ortal vein. Resection m ay be ad visable based on su b- 10% to 15% (34). The biliary d rainage to a segment or seg-
sequ ent resid u al functioning liver volum e. Once a d ecision ments of liver may be occlud ed or d ivid ed w ithin the liver.
has been m ad e w ith regard to salvage versu s resection, bile With incision into or through the liver, intrahepatic biliary
d u ct p rim ary repair, biliary enteric anastom osis, or liver inju ry w ill occur if a line of d ivision of the liver crosses the
resection shou ld be p erform ed . plane of biliary d rainage w ithout removing the portion of
When there is irretrievable liver d evascu larization, the liver that is served by that biliary d rainage. Intrahepatic bil-
only op tion may be emergency liver transplant. Bleed ing iary inju ry can also occur w ith placem ent of probes for
shou ld be controlled as m uch as possible, and contact w ith cryoablation or rad iofrequency ablation, w ith placement of
a transp lant center and w ith a liver transplant su rgeon at catheters into the liver for biliary d rainage or abscess
that center shou ld be carried out im m ed iately. Su rvival for d rainage, or w ith need le liver biopsy.
anhep atic p atients is u su ally less than 72 hours. If the bile d ucts in the isolated segm ent are com pletely
Maintenance of venou s d rainage from the resid u al liver occlu d ed , and p rovid ed that the bile w ithin the isolated
rem nant also d em and s p lanning and continu ed intraop era- segm ent rem ains sterile, the resu lt is that the isolated seg-
tive attention. Liver tissu e w ithou t venou s d rainage w ill m ent of liver w ill atrop hy. H ow ever, if the segm ent of liver
not rem ain viable. Protection of venous d rainage inclu d es associated w ith an obstru cted bile d u ct is an im portant
evalu ation for the course of the m ajor hepatic veins, cross- com p onent of the fu nctioning liver rem nant, the patient
ing them w ith resection only in a planned fashion, and m ay exp erience p ostop erative liver failu re. If the bile
evalu ation for accessory hepatic veins, w hich m ay allow w ithin an isolated bile d u ct is not sterile, a liver abscess is
partial lobe resections and / or d ivid ing a m ajor hep atic likely to resu lt. If a bile d u ct in an isolated segm ent is not
vein. In extrem e cases vein grafts can be u sed to rep lace ad equ ately occlu d ed , m ore so w ith incision through the
resected segm ents of m ajor veins (31). Care for venou s liver than w ith need le or p robe bile d u ct inju ry, a persistent
d rainage m ust avoid occlu d ing resid u al hepatic veins w ith bile leak from the su rface of the liver is likely.
ill-placed sutu res into the hepatic parenchym a in an Avoid ance of bile d u ct inju ry is the best p ractice and is
attem p t to control bleed ing. based on know led ge of liver internal anatom y, d emon-
strated by intraop erative u ltrasou nd . Su ccessful p rim ary
Bile Duct Injuries rep air of intrahep atic or extrahep atic bile d u cts m ay be
Injury to the extrahepatic bile d ucts associated w ith liver p ossible w hen th e d u cts are of relatively large caliber
surgery can be irreparable and the etiology of mortality d ue ( 3 m m d iam eter) and the inju ry d oes not involve greater
to acute hepatic failure. The bile d ucts, particularly at the than 50% of the circumference of the bile d uct. In larger
hilar plate, are more easily d isrupted than the vessels and hepatic d ucts w ith 50% circumference injury, bile d rainage
shou ld be established into a Rou x-en-Y lim b of intestine. d iaphragmatic repair rarely requires prosthetic placement.
Stenting of inju red intrahep atic bile d u cts m ay be u sed to The opening should be repaired using permanent suture
achieve tem p orary bu t not p erm anent d rainage. usually w ith a running technique. Clot and fluid shou ld be
evacuated from the pleu ral space before and d uring the
Air Embolism repair. Usu ally a chest tu be is not requ ired , if resid u al air is
Air embolism is a risk during procedures involving division aspirated from the chest cavity w ith a catheter throu gh the
of the hepatic parenchyma. Because of relatively low pres- d efect w hile the anesthetist supplies forced inspiration. The
sure in the hepatic veins there is the risk of air being d raw n catheter is w ithd raw n on suction as the last suture is tied .
into the vein and blood flow carrying that air through the
right heart and into the pulmonary arteries. The air, if volu- ■ Postoperative complications
minous enough, can cause blockage of pulm onary artery
blood flow. More feared is air that crosses an atrial septal Fulminant Hepatic Failure
defect and passes into the arterial circulation to the coronary Fulminant hepatic failure is defined as the development of
arteries or the cerebral circulation, with potentially devastat- hepatic encephalopathy w ithin 8 weeks of the patient being
ing effects. In practice, the risk of air embolism is not very healthy. The most common cause of fulminant hepatic failure
great d uring open operations on the liver because patients follow ing liver resection is a small functioning liver remnant.
are maintained on positive pressure ventilation during gen- Other etiologies include liver devascularization, interruption
eral anesthesia. The central venous pressure is therefore of venous d rainage from the liver, excessive liver warm
alw ays greater than zero, and blood exits the openings in the ischemia, major bile duct obstruction, halogenated anesthetic
veins rather than air being drawn in. The veins are very thin- agents, viral infections with hepatitis B, and reactions to cer-
w alled and collapse to a great d egree w hen central venous tain drugs. The hallmark of postoperative liver failure is a
pressure drops. Operating in the reverse-Trendelenburg persistently rising bilirubin, coagulopathy, and encephalopa-
position does d ecrease central venous pressure, but usually thy. This can be accom p anied by acid osis, renal failu re,
not so far as to result in air embolism. If there is significant and hyp oglycem ia. It is im p ortant d u ring this situ ation to
blood loss and decreasing central venous pressure, consid er- evaluate for u nrecognized vascu lar injuries that cou ld be
ing moving into a flat position is prud ent. contribu ting to the liver failu re w ith the u se of d u p lex
The risk of CO 2 em bolu s is m u ch m ore significant w ith u ltrasou nd , CT angiograp hy, or MRI. Acu te high grad e
laparoscopic liver surgery because the pressure of the CO 2 obstru ction of the biliary tree shou ld also be investigated
w ithin the p eritoneal cavity is u su ally higher than the cen- by use of magnetic resonance cholangiopancreatography
tral venou s p ressu re. Although reports of air em bolu s (MRCP), end oscop ic retrograd e cholangiop ancreatogra-
occu rring w ith lap aroscop ic p roced u res on other organs p hy (ERCP), or percu taneou s transhepatic cholangiograp hy
exist, none exist for lap aroscopic liver resection. A single (PTC) d epend ing on anatomical factors and overall index of
stu d y ad d ressing this issu e d id not cau se any significant or suspicion. Currently there is no treatment for postoperative
planned op enings into a m ajor hepatic vein or the su p ra- fulminant liver failure other than supportive care allowing
hep atic vena cava; so w hile the com plication is p ossible, its for hopeful return of liver function and recovery. Otherwise
incid ence is u nknow n (35). transplantation needs to be considered d epend ing on ongo-
Treatment for air embolus intraoperatively includes ing oncologic or infectious issues. In these circumstances,
placement of the patient in Trendelenburg position, aspira- bioartificial liver methods have been used in trials as bridges
tion of air through a central line, use of 100% inspired oxy- to transplant; however, their efficacy is still unclear (36).
gen, restoration of central venous pressure, and closure or
occlusion of the opening through which the air entered the Hepatic Insufficiency
circulation. Although recommended with air embolus, turn- Liver regeneration can rep lace the rem oved liver to a vary-
ing the patient on the left side is less feasible intraoperatively. ing extent, d ep end ing on the liver ’s health, bu t it d oes not
d o so instantaneou sly. In a norm al liver fu ll regenerative
Diaphragmatic Injury rep lacem ent after a m ajor liver resection occu rs in abou t
Occasionally a portion of the d iaphragm must be resected 6 m onths w ith over 80% of this occu rring over a 6 to 8 w eek
w hile removing a hepatic tumor. With care, injury to the p eriod . A d am aged liver regenerates less rap id ly and less
lung can be avoided , although infrequently the lung is fu lly. A gu id eline has been that in the norm al liver, a liver
adherent to the process at the d iaphragm. If no injury to the remnant of 25% to 30% of the initial liver volu me is com -
lung occurs, there usually is no compromise in respiratory p atible w ith su rvival; w ith Child A cirrhosis a liver rem -
function d uring the operation. Lung volume can be compro- nant of 40% to 50% of the initial liver volu m e is com patible
mised if large amounts of fluid fill the pleural space, leaving w ith su rvival; and w ith interm ed iate levels of liver injury,
decreased chest volume for lung expansion, or if the opening su ch as w ith fatty liver, a liver rem nant of 40% of the initial
in the diaphragm is so small that air entering the pleural liver volu m e is com p atible w ith su rvival (16,37). The
space is entrapped , causing a tension pneumothorax. am ou nt of resid u al fu nctioning liver volu m e is also influ-
There is usually no problem w ith leaving the d iaphragm enced by technical factors resu lting from the op eration:
op en u ntil after the liver resection is com p leted . The inju ry to the liver by w arm ischem ia, ad equ acy of vascular
sup p ly to the rem aining liver volum e, venou s d rainage inflow occlusion to decrease blood loss during resection, and
from the rem aining liver volu m e, and biliary d rainage. they often use it w hen d oing intraoperative liver ablations.
These factors can all influ ence the d egree of hep atic insu ffi- Lim iting th e d u ration of each in d ivid u al event of liver
ciency p ostresection. Ad d itionally, a recent stu d y has su g- inflow occlu sion seem s to d ecrease the p ostop erative
gested that laparoscopic liver resection m ay resu lt in a transaminase rise, but this practice d emand s multiple peri-
d ecreased incid ence of hepatic d ecom p ensation in cirrhotic od s of reperfusion and prolongs the time of transection, and
patients w ith sim ilar oncologic ou tcom es (38). it sometimes increases blood loss. Recently there has been a
Su bacu te hep atic failu re is d efined as the onset of trend tow ard “ischemic precond itioning,” using an initial
hep atic com a at greater than 8 w eeks from a healthy state. 10-minute period of w arm ischemia follow ed by a 10-minute
Etiologies associated w ith liver operations inclu d e sm all period of reperfusion, after w hich a continuous longer
fu nctioning liver rem nant, hep atitis B from transfu sion or stretch of w arm ischemia seems to cause less liver cell injury
reactivation associated w ith the operation (39), and p artial than the same d uration of w arm ischemia w ithout the
bile d u ct obstruction, cau sed by unrelieved choled o- “ischemic precond itioning” (43). The benefits are greatest in
cholithiasis, hep atolithiasis, or progressive strictu re d u e to younger patients, for longer d uration hepatic inflow occlu-
ischem ia or therm al inju ry. Chronic liver failure can con- sions, for resections in w hich over 50% of the liver is
tinu e to p rogress, usually in cases involving those w ith resected , and w hen there is liver steatosis. It has also been
chronic liver d isease or cirrhosis. reported that w arm ischemia is better tolerated w ith only
Shou ld hep atic insu fficiency d evelop, m easu res m u st inflow occlusion as compared to total hepatic vascular exclu-
be u nd ertaken to lim it the consequ ences of this state, su ch sion. It is postulated that there is som e liver cell perfusion
as m anagem ent of ascites w ith the use of sod iu m restric- retrograde via the hepatic veins w hen there is inflow occlu-
tion and d iu retics and m anagem ent of encep halop athy by sion w ithout outflow occlusion (26).
the u se of agents to m inim ize intestinal flora. Factors in the The tolerated length of w arm ischem ia is related to the
form ation of ascites includ e a d ecrease in seru m colloid resid u al fu nctioning liver volu m e, bu t few d ata d irectly
osm otic p ressu re and an increase in p ortal venou s p res- correlate those tw o p aram eters. For a right hepatic lobec-
sure. Seru m albu m in, the m ajor d eterm inant of seru m col- tomy in a norm al liver (averaging abou t 65% resection),
loid osm otic p ressure, is u su ally severely d epressed after w arm ischem ia is tolerated for 60 m inu tes w ithou t inter-
major liver resection—to as low as 1.6 g/ d L, w ith recovery m ittent rep erfu sion (44). With cirrhosis, w arm ischem ia can
over several w eeks to m onths. With liver resection of be tolerated u p to 30 m inu tes. H ow ever, m ost liver sur-
greater than 30%, there is an increase in portal venou s p res- geons w ho operate frequ ently on cirrhotic livers m aintain
sure (40,41). Com plications of ascites includ e ascitic leak inflow occlu sion for only 15 to 20 m inu tes, interspersed
from incisions. Pressure p henomena m ay occur, inclu d ing w ith p eriod s of 5 to 10 m inu tes of rep erfu sion.
abd om inal p ain d u e to the d istention, early satiety and
vom iting d u e to com p ression of the stom ach and intes- Liver Devascularization
tines, and abd ominal com partm ent synd rom e. Infected
ascites, second ary to contam ination throu gh d rain tracts, Fulminant hepatic failure w ill occur rapid ly with total
incisions, or from p aracenteses, m ay also occu r. d evascularization of a normal liver and occurs w ith less than
In patients w ith cirrhosis and in those w ith m ajor liver total d evascularization of a cirrhotic or otherw ise damaged
resection, immed iate postoperative treatment w ith spirono- liver. Intraoperatively recognized d evascularization is d is-
lactone and avoid ance of high postoperative central venou s cussed above. Unrecognized devascularization can occur
pressu re (w hich is a p artial d eterminant of portal venous intraoperatively, and postoperative portal venous or hepatic
pressu re) may help to d ecrease the rate of formation of artery thrombosis can occur d ue to operative injury or d ue to
ascites. Paracentesis may be requ ired in cases of su sp ected a hypercoagulable state. Avoid ance of d evascularization
infected ascites (d iagnostic) or in cases of com p ressive postoperatively includ es respectful hand ling of the hilar
symptoms (therapeutic) and should be performed und er blood vessels d uring operation and investigation of any sus-
ultrasound guid ance. Drains in p atients w ith ascites shou ld pected hypercoagulable states preoperatively so that appro-
be avoid ed and , if p laced , shou ld be removed early and the priate postoperative prophylaxis may be implemented .
tract closed to prevent ascitic leak. Ind eed , a rand omized Thrombosis of major hepatic arteries or the portal vein post-
prospective trial show ed that u se of d rains in cirrhotic operatively may be detected by power Doppler ultrasound,
patients w ith ascites resu lted in higher infectious comp lica- arterial and portal venous phase CT, or MRI. With early
tion rates (42). d etection of hepatic artery or portal vein thrombosis and evi-
d ence of compromised liver function, treatment w ith
Warm Ischemia catheter-directed thrombolysis, operative thrombectomy,
Warm ischemia is associated w ith injury to liver cells. Warm and / or vascular repair may be lifesaving (45).
ischemia causes a postoperative rise in transaminases,
w hich usually peak at about 24 to 48 hours; this increase is Biloma
proportional to the length of the warm ischemia and the An intra-abd om inal collection of bile, or bilom a, occu rs in
overall health of the liver remnant. Most liver surgeons use abou t 3% of p atients after m ajor liver resection, and to a
lesser extent after m inor liver resection or w ith d rainage of asp iration of bile. Appropriate placement of closed suction
liver abscess (1). Partial excision or enu cleation of a biliary drains follow ing liver operations can usually prevent bile
cystad enom a also has a m od erate risk of bilom a. Bilom a peritonitis. The d rains should be left in place for 3 to 4 days to
can be lessened by m eticu lou s d etection and closu re of all allow any bile leakage to become manifest. Drain fluid
sites of bile d rainage on the raw surface of the liver. Placing should be checked for bile before removing the drain.
d rains at the tim e of operation d oes not lessen bile leak- Treatm ent of bile p eritonitis requ ires d rainage of the
associated comp lications, bu t d rainage w ith a closed sys- leaking bile. Treatm ent often also requ ires d ecom pression
tem is m ore likely to convert a bilom a to a biliary fistu la as of the biliary tree by end obiliary stent or p ercu taneou s
w ell as to avoid an infected bilom a or bile p eritonitis. transhep atic biliary d rain. In cases w here the leaking bil-
Sym p tom s and signs of u ninfected bilom a m ay be m in- iary system is not in continuity w ith the m ain biliary tree,
im al. There m ay be right u pper quad rant or epigastric d is- d raining the m ain bile d u cts w ill not be effective in d ecreas-
com fort and tend erness, rarely a palpable m ass, and often a ing the bile leak (see the follow ing section, “Biliary Fis-
minor rise in seru m bilirubin. Diagnosis is by u ltrasonogra- tu la”). Althou gh d rainage of biliary ascites m ay be possible
phy or CT, com bined w ith d iagnostic aspiration of biliou s p ercu taneou sly, effective d rainage m ay requ ire laparo-
fluid . Treatm ent is tu be d rainage, w hich is usually possible tomy, evacu ation of bile, irrigation of the abd om en, and
percutaneou sly. Persistent bile d rainage ind icates a biliary d irected p lacem ent of d rains.
fistu la. Fever, tachycard ia, and abd om inal pain m ay
d evelop in cases of an infected bilom a. The treatm ent is Biliary Fistula
antibiotics and p ercu taneous tube d rainage. Postoperative biliary fistula is most frequently a biliary-cuta-
neous fistula, as represented by bile drainage through an
Bile Peritonitis operatively placed d rain. A biliary-cutaneous fistula can also
Bile peritonitis results from bile accessing the general peri- occur through a drain site after removal of the d rain or
toneal cavity rather than being w alled off into a discrete col- through the operative w ound or laparoscopic port sites.
lection. Bile peritonitis is usually associated w ith insidious Occasionally, undrained bile, usually infected, w ill erode
onset of symptoms, including ileus, malaise, abdominal dis- through the diaphragm into a bronchus or into a gastroin-
tention, and, eventually, peritoneal signs. The initial peritoni- testinal viscus. Persistent biliary fistula is almost always asso-
tis is chemical, but often bacteria are present and infectious ciated w ith a bile duct that has no free-flowing drainage to
peritonitis su bsequ ently d evelops. Making the d iagnosis of the intestine. Such situations includ e bile drainage from an
bile p eritonitis requ ires an aw areness of the subtlety of ini- excluded biliary system (Fig. 34.1) or from a source proximal
tial sym p tom s and signs and an abd om inal u ltrasou nd or to an obstructed bile d uct. Etiologies of bile duct obstruction
CT d em onstrating intra-abd om inal fluid , confirm ed by include iatrogenic occlusion (clip, ligature, thermal injury),
A B
FIGURE 34.1. Isolated bile duct after nonanatomic liver resection. A: anteroposterior view; B: lateral view.
bile d u ct stone, bile d u ct hem atom a, tum or involving the

bile d u ct or com pressing the bile d u ct, bile d u ct p arasite,
inflam m atory-associated stenosis, or ischem ic or rad iation-
associated strictu re.
Postop erative bile fistu la, if confined to a d rain, shou ld
not be treated by early d rain w ithd raw al (46). The d rain
shou ld be left in place long enou gh to allow form ation of a
fibrou s tract arou nd the d rain—4 to 6 w eeks, or longer if
the p atient is m alnourished or on steroid s. In the m ajority
of cases the fistu la w ill heal by 4 w eeks w ithout any ad d i-
tional interventions. If bile leakage continu es, the etiology
of the d rainage is one of the cond itions listed above, or the
d rain m ay be lying im m ed iately on the leak point, p revent-
ing healing. The safest cou rse w ith p ersistent bile d rainage
is to p erform a rad iocontrast d rain injection stu d y, w ith
gravity or very gently injected instillation of contrast to
d eterm ine: (a) if the d rain is im m ed iately against the open-
ing in the biliary tree, (b) if there is an isolated biliary seg-
ment, and (c) if there is d istal obstruction of the visu alized FIGURE 34.2. Ischemic bile duct injury after ligation of hepatic arterial
blood supply. The arrows outline the area of ischemic stricture.
biliary tree. With the first circum stance, w ithd raw al of the
d rain beyond the point of contact w ith the biliary tree w ill
perm it scar to close the opening in the biliary tree, and u su -
ally the bile leak w ill resolve, after w hich the d rain can be Biliary Stricture or Obstruction
grad u ally w ithd raw n. Alternatively, ERCP w ith stent and Biliary stricture follow ing operation or surgical intervention
sp hincterotom y m ay be p erform ed to allow the bile to p ref- may result from mechanical injury by a scalpel, biopsy nee-
erentially flow into the d u od enum rather than into the d le, ablation probe, or d rainage catheter; from thermal injury
d rain allow ing su bsequent d rain rem oval and healing of w ith cautery, laser, radiofrequency ablation, cryoablation, or
the biliary leak. laser probe ablation; from ischemia due to devascularization
When an isolated segm ent of bile d u ct is fou nd , the of the bile duct (Fig. 34.2); or from chemical injury with
problem is m ore d ifficu lt. By this p oint the bile m ay have hypertonic saline or formalin or other chemical scolicidal
becom e contaminated w ith bacteria. Although w ithd raw al solution in the treatment of echinococcal cyst. Avoidance of
of the d rain after a d rain tract has form ed m ay resu lt in clo- bile duct stricture should always be the goal, because treat-
sure of the fistu la, there is also a chance that fistu la w ill ment may be very complicated and the potential complica-
recu r or that cholangitis or liver abscess, or both, w ill tions associated w ith bile duct stricture can be devastating.
resu lt. Measu res that have been su ccessful for treatm ent of The first and major step in avoid ance of bile d uct strictures is
the isolated biliary segm ent inclu d e injection w ith tetracy- recognition of the variety of mechanisms that can cause these
cline or w ith fibrin glu e. In cases in w hich treatm ent by problems and care in the use of such modalities.
these measu res fails, reoperation w ith resection of the iso- The resu lts of bile d u ct strictu re are varied and d ep end
lated biliary segm ent m ay be requ ired . If the bile d u ct on w hether there is comp lete or p artial obstru ction and on
d raining the isolated segm ent is large and a 1-cm or larger the p rop ortion of liver that is involved . H igh-grad e stric-
mu cosa-to-m u cosa anastomosis can be created , Rou x-en-Y tu re obstructing bile egress from the entire liver is associ-
biliary-enteric reconstru ction is an op tion. ated w ith jau nd ice and , if u nalleviated , liver failure. In
When d istal obstru ction of the biliary tree is resp onsible situations in w hich the bile is sterile and the liver
for p ersistent biliary fistu la, the focu s of treatm ent shou ld p arenchym a is relatively norm al, high-grad e strictu re of
be d irected to the d istal strictu re (d iscussed below ), the bile d u cts proxim al to the main bile d u ct m ay prove
su ccessfu l treatm ent of w hich u su ally allow s resolu tion of innocu ou s. The liver su bserved by the obstru cted bile d u ct
the fistu la (47). w ill atrop hy, and the liver w ith norm al bile d u ct d rainage
If the bile d rainage is not throu gh a d rain, investiga- w ill hyp ertrop hy. If the p ortion of liver su bserved by the
tion shou ld begin w ith CT, looking for p arahep atic flu id obstru cted bile d u ct is sm all, the d am age in the sterile situ-
collection, intrahep atic flu id collection, and biliary tract ation is likely to be insignificant. Even w ith up to 50% of
d ilation d enoting biliary obstru ction. Extrahep atic flu id the liver su bstance obstru cted , in the absence of infection,
shou ld be sam p led by im age-gu id ed need le asp iration early sym p tom s or signs are u nlikely. Intrahepatic stone
and d rained if p u ru lent or biliou s. The treatm ent of the form ation is u nlikely, becau se at a p ressu re of 40 m m H g,
d rain is then as ou tlined above. If there is evid ence of d is- bile form ation in the associated hepatocytes stops and the
tal biliary obstru ction, fu rther evalu ation w ith MRCP, com p onents necessary to form stones are absent. Although
PTC, or ERCP is ind icated . Percu taneou s or end obiliary serum alkaline phosphatase w ill be elevated in su ch a situ-
stent p lacem ent m ight be ind icated for tem p orary relief of ation, the biliru bin w ill often rise only m ild ly. The tw o
the obstru ction to p rom ote resolu tion of the fistu la. p otential com plications are (a) infection of the bile in the
obstru cted biliary tree, w ith resu lting cholangitis, liver hem obilia, the feed ing vessel is m ore often an artery than a
abscess, or both, and (b) increased risk of cholangiocarci- portal vein branch or a hepatic vein branch. Arterial p res-
noma associated w ith chronically obstru cted bile d ucts. sure is more likely to cause continued bleed ing d espite
Obstru ctions that are not high-grad e are m ore likely to increased biliary p ressures associated w ith the form ation of
be associated w ith intrahepatic d uct stone form ation. clot in the bile d ucts.
Whether there is an increased risk of cholangitis w ith intra- Diagnosis is m ad e by a com bination of stu d ies in corre-
hep atic d u ct stone form ation is unknow n. Intrahepatic bile lation w ith sym ptom s: find ing blood in the stool or
d u ct stone form ation is likely to w orsen the effects of a low - hematem esis, w ithou t a lesion to exp lain the bleed ing in
grad e strictu re, p otentially converting it to the equ ivalent the gastrointestinal tract on end oscop y; by observing blood
of a high-grad e strictu re. com ing from the papilla of Vater on upp er end oscop y; by
Low -grad e strictu re of the m ain bile d u ct or of the biliary d ilation on u ltrasou nd or CT w ith high-d ensity
d rainage to m any portions of the liver is likely to resu lt in m aterial w ithin the bile d u cts; by d em onstration of irregu -
second ary biliary cirrhosis. The progress to second ary bil- lar filling d efects in the bile d ucts on cholangiography;
iary cirrhosis m ay be occu lt, the risk of the occurrence w ith d em onstration of entry of contrast into a vessel on
d enoted only by an elevated alkaline phosphatase. Liver cholangiography; and by d em onstration of hepatic artery
biopsy m ay be the only m ethod to d eterm ine w hether cir- p seu d o-aneu rysm or contrast entering the biliary tree on
rhosis has d evelop ed . Becau se the occu rrence of second ary visceral angiograp hy. Resolu tion can be sp ontaneous; how -
biliary cirrhosis is variable, persistently elevated alkaline ever, treatm ent of p ersistent or m assive hem obilia by
phosp hatase shou ld p rom pt investigation by im aging hep atic artery em bolization is u su ally effective. Qu ite infre-
stu d ies looking for intrahep atic bile d u ct d ilation. qu ently, hep atic artery ligation or hep atic resection of the
Early treatm ent of bile d u ct strictu re is im p ortant before affected area of liver is requ ired .
atrop hy or second ary biliary cirrhosis occu rs and consists
of reestablishm ent of free, low -pressu re d rainage from the Cholangitis
affected bile d u cts. Treatm ents for strictu re includ e balloon If there is n o free bile d rain age p ostop eratively after liver
cholangiop lasty via ERCP or PTC com bined w ith p lastic su rgery and if the biliary tree has been seed ed w ith
external, internal, or internal/ external d rains/ stents, or organ ism s, ch olan gitis can occu r. Most critical in treating
biliary-enteric anastom osis. Stents have a lim ited lifetim e and avoid ing cholangitis is the intraop erative establish-
(u su ally less than 16 w eeks) because of bu ild u p of bile salts m ent and postoperative maintenance of ad equate biliary
and proteinaceou s m aterial on the plastic, w ith occlu sion d rainage. At op eration, that goal includ es assessm ent of bil-
and reobstru ction and / or cholangitis. Internal expand able iary d rainage, removal of obstru cting d ebris su ch as stones,
metal stents have a longer lifetim e, but have a m axim al and constru cting a generou s anastomosis w henever p ossi-
useful effectiveness w ith benign strictures of abou t 5 years ble. Treatm ent of early p ostop erative cholangitis is w ith
(48) and cannot be changed . For strictu res that cannot be antibiotics and institu tion of free biliary d rainage.
ad equ ately treated w ith balloon cholangioplasty, biliary- Cholangitis m ay occur at months to years after liver sur-
enteric anastom osis should be perform ed , if possible. For gery, usually resulting from restricted d rainage of contami-
strictu res that cannot be ad equ ately treated w ith serial d ila- nated bile w ith the most common etiologies being listed in
tions or biliary-enteric anastom osis, consid eration shou ld Table 34.7. Investigation should inclu d e d etermination of
be given to resection of the affected portion of the liver, if seru m alkaline phosphatase levels and biliru bin. Evalu ation
an ad equ ate liver rem nant can be left. Su ch a resection
avoid s the risk of recurrent cholangitis and liver abscess
and the m ore d istant risk of cholangiocarcinom a. Table 3 4 .7 Et iologies of ch ola n git is a ft er
liver su r ger y
Hemobilia
H em obilia, bleed ing into the bile d u cts, can occu r after liver Common bile duct stones
resection from d irect trauma, such as w ith core need le Benign biliary stricture
biopsy d uring a p roced u re on the liver, abscess erod ing into Malignant biliary stricture
both bile d u ct and ad jacent vessel, communication of bile
Biliary-enteric anastomotic stricture
d uct and vessel w ithin a postoperative hem atoma, arterial
pseud oaneu rysm rup tu ring into a bile d uct, or inju ry to Biliary-enteric stent
both bile d u ct and a vessel d u e to rad iofrequency ablation, Percutaneous transhepatic biliary drain
cryoablation, or laser ablation of a liver lesion. Etiologies Percutaneous transhepatic cholangiography
also includ e bleed ing from tu mor w ithin bile d ucts, su ch as
Endoscopic retrograde cholangiography
hepatocellular carcinom a or bile d uct m alignancies.
Manifestations are most commonly right upper quad - Biliary-enteric fistula
rant pain, jaund ice, and hem atemesis, but also inclu d e Common bile duct parasites
occult unexplained blood loss, melena or hematochezia, Recurrent pyogenic cholangitis
hyperbiliru binem ia, and acu te p ancreatitis. With significant
also requ ires imaging—first, of the biliary tree to assess for high u rine-to-p lasm a ratios of creatinine. The d iagnosis
site(s) of stricture and for the presence of biliary stones; sec- and treatm ent of the com m on cau ses of renal failu re are
ond , of the surround ing structures to d etect extrinsic tissue those em p loyed in the p ostop erative setting and are not
causing biliary obstruction, such as intrahepatic or extra- u niqu e to liver su rgery. H ep atorenal synd rom e has no
hepatic tumor, lymphad enopathy, pseud ocyst, or abscess; w ell-established m echanism , althou gh elevation of vari-
and , third , of the liver to su rvey for hep atic abscess and for ou s cytokines, inclu d ing end othelin-1, and d ecreases in
partial liver atrophy. Ultrasonography should serve as an certain p rostagland ins have been im p licated . H ep atorenal
initial screen. If cholangitis is su spected , CT or MRI/ MRCP synd rom e is invariably lethal after liver su rgery u nless
should be performed . treated by liver transp lantation.
The long-term solu tion to cholangitis is to obtain ad e-
qu ate and p erm anent biliary d rainage. Becau se of the vari- Gastrointestinal Bleeding
ety of etiologies, there is no single solu tion. Occasionally, GI bleeding after liver surgery in the noncirrhotic patient
sym p tom s and signs of cholangitis w ill occu r in som e ind i- occurs in less than 1% of patients (1) and is predominantly
vid u als w ithou t evid ence of inad equate biliary d rainage. In d ue to gastric erosions or ulceration associated w ith postop-
these ind ivid u als su p p ortive treatm ent is all that can be erative sepsis. Stress ulceration can largely be avoid ed w ith
offered , bu t reevaluation should be carried out at intervals agents that maintain the postoperative gastric pH greater
if sym ptom s and signs continue. than 5, such as H 2-blockers or proton pum p inhibitors. Other
etiologies include postoperative coagulopathy and hemo-
Intrahepatic Abscess bilia. In patients w ith cirrhosis w ith portal hypertension,
Intrahep atic abscess m ay resu lt as a com p lication of liver bleed ing may also occur from esophagogastric varices or
surgery w hen there is cholangitis, w hen there is focal bile from portal gastropathy.
d u ct obstru ction w ith the obstru cted bile d u ct becom ing
second arily infected , or w hen an intrahepatic hem atom a
becom es second arily infected . If lim ited in num ber and less
■ SUMMARY
than 2 to 3 cm in size, hepatic abscesses m ay be d rained Liver su rgery and p roced u res can be d one safely at institu -
percu taneou sly and treated w ith antibiotics. Sm aller tions w here high volu m es of su ch surgery are perform ed .
abscesses w ill often resolve w ith antibiotic treatm ent alone. Safety involves experience w ith the p atient evaluation,
Investigation for obstru cted bile d u cts shou ld be u nd er- selection for p roced u res, p erform ance of the operations,
taken w henever hepatic abscess occu rs, but treatm ent and p ostop erative care. Safety also involves recognition of
shou ld not aw ait this evalu ation. When there is no resolu - p ossible com p lications associated w ith p roced u res, avoid -
tion of the abscess or there is occu rrence of ad d itional ance w henever p ossible, and exp ed itiou s treatm ent of com -
abscesses, reevaluation shou ld be consid ered . Occasion- p lications w hen they occu r.
ally, op erative d rainage is requ ired for m u ltiple abscesses
or failu re of p ercu taneou s therap y.
■ REFERENCES
Parahepatic Abscess 1. Jarnagin WR, Gonen M, Fong Y, et al. Im p rovem ent in p eriop erative
Parahep atic abscess occurs rarely and is u su ally associated ou tcom e after hepatic resection: analysis of 1,803 consecu tive cases
over the p ast d ecad e. Ann Surg 2002;236:397–406; d iscu ssion 406–397.
w ith factors su ch as an infected bilom a or infected 2. McKay A, You I, Bigam D, et al. Im pact of su rgeon training on outcom es
hem atom a. Meticulous hemostasis, closure of any sites of after resective hep atic surgery. Ann Surg Oncol 2008;15:1348–1355.
bile leakage, and avoid ance of postoperative coagu lop athy 3. Gagner M, Franco D, Vons C, et al. Analysis of m orbid ity and m ortality
rates in right hep atectom y w ith the preoperative APACH E II score.
are the p rim ary m eans of preventing parahepatic abscess. Surgery 1991;110:487–492.
Placem ent of closed suction d rains, m aintained for only a 4. Teh SH , Christein J, Donohu e J, et al. H ep atic resection of hep atocellu -
lim ited tim e p ostoperatively, m ay d ecrease the incid ence of lar carcinom a in patients w ith cirrhosis: Mod el of End -Stage Liver Dis-
ease (MELD) score p red icts p eriop erative m ortality. J Gastrointest Surg
infected bilom a as the source of parahepatic abscess. Treat- 2005;9:1207–1215; d iscu ssion 1215.
ment of parahepatic abscess is percutaneou s d rainage and 5. Belghiti J, H iram atsu K, Benoist S, et al. Seven hu nd red forty-seven
antibiotics, similar to the treatm ent of other postop erative hep atectom ies in the 1990s: an u p d ate to evalu ate the actu al risk of
liver resection. J Am Coll Surg 2000;191(1):38–46.
intra-abd om inal abscesses. 6. Asiyanbola B, Chang D, Gleisner AL, et al. Op erative m ortality after
hepatic resection: are literatu re-based rates broad ly applicable? J Gas-
Renal Failure trointest Surg 2008;12:842–851.
7. Bru ix J, Castells A, Bosch J, et al. Su rgical resection of hep atocellu lar
Renal failu re as a com p lication of liver su rgery m ay have carcinom a in cirrhotic patients: prognostic value of preoperative portal
a nu m ber of etiologies, inclu d ing hyp otension d u e to pressu re. Gastroenterology 1996;111:1018–1022.
blood loss or sep sis, toxic inju ry from nep hrotoxic d ru gs, 8. H ashim oto M, Watanabe G. H ep atic p arenchym al cell volu m e and the
ind ocyanine green tolerance test. J Surg Res 2000;92:222–227.
inad equ ate flu id ad m inistration or excessive flu id loss 9. Wakabayashi H , Ishim ura K, Izu ishi K, et al. Evalu ation of liver fu nc-
w ith d iu retic u se, or, u ncom m only, hep atorenal synd rom e tion for hep atic resection for hepatocellu lar carcinom a in the liver w ith
in p atients w ith cirrhosis or liver failu re. Characteristic of d am aged p arenchym a. J Surg Res 2004;116:248–252.
10. H em m ing AW, Gallinger S, Greig PD, et al. The hip p u rate ratio as an
the hep atorenal synd rom e are a u rine sod iu m concentra- ind icator of functional hepatic reserve for resection of hep atocellu lar
tion of less than 10 m Eq/ L, high u rine osm olality, and carcinom a in cirrhotic p atients. J Gastrointest Surg 2001;5:316–321.
11. Selzner M, Clavien PA. Fatty liver in liver transp lantation and su rgery. 30. Cohen AM, H iggins J, Waltm an AC, et al. Effect of ligation of variant
Semin Liver Dis 2001;21:105–113. hepatic arterial stru ctu res on the com pleteness of regional chem other-
12. Clavien PA, Em ond J, Vau they JN , et al. Protection of the liver d u ring ap y infu sion. Am J Surg 1987;153:378–380.
hep atic surgery. J Gastrointest Surg 2004;8:313–327. 31. Sano K, Maku u chi M, Miki K, et al. Evalu ation of hep atic venou s con-
13. Shou p M, Gonen M, D’Angelica M, et al. Volu m etric analysis pred icts gestion: p rop osed ind ication criteria for hep atic vein reconstru ction.
hep atic d ysfu nction in p atients u nd ergoing m ajor liver resection. J Gas- Ann Surg 2002;236:241–247.
trointest Surg 2003;7:325–330. 32. H ealey JE Jr, Schroy PC. Anatom y of the biliary d u cts w ithin the
14. Abd alla EK, Denys A, Chevalier P, et al. Total and segm ental liver vol- hum an liver; analysis of the prevailing pattern of branchings and the
u m e variations: im p lications for liver surgery. Surgery 2004;135:404–410. m ajor variations of the biliary d u cts. AMA Arch Surg 1953;66:599–616.
15. Vau they JN , Chaou i A, Do KA, et al. Stand ard ized m easu rem ent of the 33. Figu eras J, Lopez-Ben S, Llad o L, et al. H ilar d issection versu s the “glis-
future liver rem nant prior to extend ed liver resection: m ethod ology sonean” ap p roach and stap ling of the p ed icle for m ajor hep atectom ies:
and clinical associations. Surgery 2000;127:512–519. a p rospective, rand om ized trial. Ann Surg 2003;238:111–119.
16. Azoulay D, Castaing D, Krissat J, et al. Percutaneous portal vein 34. Yam ashita Y, H am atsu T, Rikim aru T, et al. Bile leakage after hep atic
embolization increases the feasibility and safety of major liver resection resection. Ann Surg 2001;233:45–50.
for hepatocellular carcinoma in injured liver. Ann Surg 2000;232:665–672. 35. Ricciard i R, Anw aru d d in S, Schaffer BK, et al. Elevated intrahep atic
17. Wakabayashi H , Ishim u ra K, Okano K, et al. Ap p lication of p reopera- p ressu res and d ecreased hep atic tissue blood flow prevent gas em bolu s
tive p ortal vein em bolization before m ajor hep atic resection in p atients d uring lim ited lap aroscop ic liver resections. Surg Endosc 2001;15:
w ith norm al or abnorm al liver p arenchym a. Surgery 2002;131:26–33. 729–733.
18. Ad am R, Laurent A, Azou lay D, et al. Tw o-stage hep atectom y: A 36. Dem etriou AA, Brow n RS Jr, Bu su ttil RW, et al. Prosp ective, rand om -
p lanned strategy to treat irresectable liver tu m ors. Ann Surg 2000;232: ized , m ulticenter, controlled trial of a bioartificial liver in treating acu te
777–785. liver failu re. Ann Surg 2004;239:660–667; d iscu ssion 667–670.
19. Kooby DA, Stockm an J, Ben-Porat L, et al. Influ ence of transfu sions on 37. Farges O, Belghiti J, Kianm anesh R, et al. Portal vein em bolization
p erioperative and long-term ou tcom e in p atients follow ing hep atic before right hep atectom y: prosp ective clinical trial. Ann Surg 2003;237:
resection for colorectal m etastases. Ann Surg 2003;237:860–869; d iscu s- 208–217.
sion 869–870. 38. Laurent A, Cherqu i D, Lesu rtel M, et al. Lap aroscop ic liver resection for
20. Step henson KR, Steinberg SM, H u ghes KS, et al. Periop erative blood su bcap su lar hep atocellu lar carcinom a com p licating chronic liver d is-
transfu sions are associated w ith d ecreased tim e to recu rrence and ease. Arch Surg 2003;138:763–769; d iscu ssion 769.
d ecreased su rvival after resection of colorectal liver m etastases. Ann 39. Ku bo S, N ishigu chi S, H am ba H , et al. Reactivation of viral rep lication
Surg 1988;208:679–687. after liver resection in p atients infected w ith hep atitis B viru s. Ann Surg
21. Yam am oto J, Kosuge T, Takayam a T, et al. Periop erative blood transfu - 2001;233:139–145.
sion p rom otes recu rrence of hep atocellu lar carcinom a after hep atec- 40. N agasu e N , Yu kaya H , Ogaw a Y, et al. Portal p ressu re follow ing p artial
tom y. Surgery 1994;115:303–309. to extensive hepatic resection in patients w ith and w ithout cirrhosis of
22. Katz SC, Shia J, Liau KH , et al. Op erative blood loss ind ep end ently p re- the liver. Ann Chir Gynaecol 1983;72:18–22.
d icts recu rrence and su rvival after resection of hep atocellu lar carci- 41. Kanem atsu T, Takenaka K, Fu ru ta T, et al. Acu te p ortal hyp ertension
nom a. Ann Surg 2009;249:617–623. associated w ith liver resection. Analysis of early p ostop erative d eath.
23. Paquet JC, Dziri C, H ay JM, et al. Prevention of d eep abd om inal com - Arch Surg 1985;120:1303–1305.
p lications w ith om entop lasty on the raw su rface after hep atic resection. 42. Liu CL, Fan ST, Lo CM, et al. Abd om inal d rainage after hep atic resec-
The French Associations for Su rgical Research. Am J Surg 2000;179: tion is contraind icated in p atients w ith chronic liver d iseases. Ann Surg
103–109. 2004;239:194–201.
24. Chen H , Merchant N B, Did olkar MS. H ep atic resection u sing interm it- 43. Clavien PA, Selzner M, Ru d iger H A, et al. A p rosp ective rand om ized
tent vascu lar inflow occlu sion and low central venou s p ressu re anes- stud y in 100 consecutive p atients u nd ergoing m ajor liver resection
thesia im proves m orbid ity and m ortality. J Gastrointest Surg 2000;4: w ith versu s w ithout ischem ic p recond itioning. Ann Surg 2003;238:
162–167. 843–850; d iscu ssion 851–842.
25. Sm yrniotis V, Kostopanagiotou G, Theod oraki K, et al. The role of cen- 44. Elias D, Lasser P, Debaene B, et al. Interm ittent vascu lar exclu sion of
tral venou s p ressu re and typ e of vascu lar control in blood loss d u ring the liver (w ithou t vena cava clam p ing) d u ring m ajor hep atectom y. Br J
m ajor liver resections. Am J Surg 2004;187:398–402. Surg 1995;82:1535–1539.
26. Sato T, Kurokaw a T, Ku sano T, et al. Up take of ind ocyanine green by 45. Stange BJ, Glanem ann M, N u essler N C, et al. H ep atic artery throm bo-
hep atocytes und er inflow occlu sion of the liver. J Surg Res 2002;105: sis after ad ult liver transp lantation. Liver Transpl 2003;9:612–620.
81–85. 46. Reed DN Jr, Vitale GC, Wrightson WR, et al. Decreasing m ortality of
27. Kaneko H , Otsuka Y, Takagi S, et al. H ep atic resection u sing stapling bile leaks after elective hep atic su rgery. Am J Surg 2003;185:316–318.
d evices. Am J Surg 2004;187:280–284. 47. Bhattacharjya S, Pu leston J, David son BR, et al. Ou tcom e of early end o-
28. Jiao LR, Ayav A, N avarra G, et al. Lap aroscop ic liver resection assisted scop ic biliary d rainage in the m anagem ent of bile leaks after hep atic
by the lap aroscopic H abib Sealer. Surgery 2008;144:770–774. resection. Gastrointest Endosc 2003;57:526–530.
29. Cu rro G, H abib N , Jiao L, et al. Rad iofrequ ency-assisted liver resection 48. Du m onceau JM, Deviere J, Delhaye M, et al. Plastic and m etal stents for
in patients w ith hep atocellu lar carcinom a and cirrhosis: prelim inary p ostoperative benign bile d u ct strictu res: the best and the w orst. Gas-
resu lts. Transplant Proc 2008;40:3523–3525. trointest Endosc 1998;47:8–17.
CHAPTER
35
Complications of Biliary Surgery

Christopher J . Sonnenday
■ INTRODUCTION ative pain, shorter hospital stay, earlier return to w ork, and
better cosmetic outcome (3). Safety and efficacy have been
Biliary tract d isease rep resents one of the m ost com m only d emonstrated in high-risk patients, such as the elderly, cir-
encou ntered clinical problems for the general su rgeon, and rhotics, and pregnant w omen (4–8). These valid ated ad van-
collectively biliary p roced u res are am ong the m ost p reva- tages, and importantly patient and surgeon preference, have
lent op erations. From the stand point of postoperative com - established laparoscopic cholecystectomy as the stand ard
plications, biliary p roced ures can be categorized as either proced ure for nearly all ind ications for gallblad d er excision
excisional (e.g., cholecystectom y) or reconstructive (e.g., w ith the notable exception of gallbladder carcinoma.
biliary–enteric anastom osis). Com plications inclu d e bile Despite the well-established role of laparoscopic chole-
leak, bile d u ct obstru ction or strictu re, and infection. Prin- cystectomy, evidence persists that the risk of the most feared
cip les that ap p ly to the m anagem ent of all com p lications of complication of cholecystectomy—bile d uct injury—remains
biliary tract operations includ e control of infection and more common than the historical rate of injury sustained
preservation or m aintenance of biliary d rainage. Maintain- d uring open cholecystectomy. Roslyn et al. (9) reported the
ing attention to these p rincip les can convert p otentially results of over 42,000 open cholecystectomies performed in
life-threatening and com p lex biliary comp lications to chal- the United States in 1989; the incidence of biliary injury in this
lenging bu t m anageable clinical problem s. All the com p li- series w as 0.2%. In a similar study performed in 1980, the
cations d iscu ssed in this chap ter w ill em p hasize ad herence incidence of major bile duct injury after open cholecystec-
to these tw o general principles. tomy was 0.3% (10). Analyses of population level data sug-
gest that the rate of bile duct injury d uring laparoscopic
■ COMPLICATIONS OF CHOLECYSTECTOMY cholecystectomy is probably two-fold higher than these his-
toric rates for open cholecystectomy. Flum et al. (11) detected
More than 700,000 cholecystectomies are performed annu- a 0.5% incidence among Medicare beneficiaries in the United
ally in the United States, reflecting the significant burd en of States and brought attention to the nearly three-fold greater
gallstone-related d isease on the healthcare system (1). It is mortality risk among cholecystectomy patients w ho sustain a
estimated that at least 20 to 25 million ad ults in the United bile duct injury. Similar national data sources from Europe
States have gallstones, and more than $6.5 billion is spent on suggest an incidence of 0.4% (12,13). Interestingly, the inci-
gallstone-related problems (2). Presentations of gallstones d ence of bile duct injury has not improved substantially now
includ e biliary colic, acute cholecystitis, chronic cholecysti- that basic laparoscopic techniques are part of the practice of
tis, biliary pancreatitis, and choledocholithiasis. Other indi- most general surgeons, and all trainees of the last decad e
cations for cholecystectomy includ e acalculous cholecystitis have had significant laparoscopic exposure and training
and biliary d yskinesia. Cholecystectomy, performed w ith en benchmarks. An interesting study from Archer et al. (14) at
bloc partial hepatectomy and portal lymphad enectomy, is least partially debunks the myth of the “learning curve,” as
also performed in select cases of gallblad d er carcinoma. surgical experience and specifically the number of laparo-
Cholecystectomy may also be included as part of a number scopic cholecystectomies performed did not appear to d imin-
of hepatobiliary and pancreatic procedures performed for ish the risk of bile duct injury.
other indications. In this section of the chap ter, m ajor com plications of
The vast majority of cholecystectomies performed for cholecystectom y w ill be consid ered , inclu d ing
gallstone d isease are currently accomplished w ith mini-
mally invasive techniques. Laparoscopic cholecystectomy is ■ Bile d u ct inju ry
the most w ell-established minimally invasive general sur- ■ Retained com m on bile d u ct stones
gery operation, w ith demonstrated benefits of less postoper- ■ Unrecognized gallblad d er cancer
Minor complications of cholecystectomy are worth con-
Christopher J. Sonnenday: The University of Michigan, sideration and can lead patients to seek care in the postopera-
Ann Arbor, MI 48109. tive period. Few of these complications are of any permanent
429
consequence, but all concerning symptoms following chole- the triangle of Calot; and inju ry to an aberrant or low -
cystectomy should be thoroughly investigated to determine inserting right hepatic d uct (17,20). All these injuries seem to
that the patient does not have a biliary injury. Taking the result from a similar anatomic misperception, specifically
approach that any postcholecystectomy problem could rep- the error of unknow ingly d issecting too closely to either the
resent, a biliary injury will serve surgeons well, as these com- common hepatic or right hepatic d uct w hen the surgeon
plications are much easier to manage the more efficiently believes he or she has ample room for dissection (17).
they are diagnosed sparing the patient the risk of sepsis and Clearly, the most effective means of ad d ressing bile d uct
liver dysfunction . injury is prevention, particularly now that the mechanism of
injury has been well described . To that end, it is worth con-
sid ering the method s commonly d escribed for accurate cys-
■ BILE DUCT INJURYFROM CHOLECYSTECTOMY
tic d uct id entification. The first, or “infund ibular,” method
■ Mechanism and prevention of bile duct injury involves dissection of the cystic duct along its anterior and
posterior aspects in the triangle of Calot. Confirmation of the
Thanks to the research of exp ert su rgeons su ch as Way, anatomy is noted by seeing a “flair” as the cystic duct
Strasberg, and others, the m echanism responsible for bile w id ens to become the infund ibulum of the gallblad d er neck.
d u ct injury d u ring lap aroscopic cholecystectom y has been This technique is w id ely used and is end orsed by many
w ell stu d ied and d escribed (10,15–17). Bile d uct inju ry is major surgical texts (21,22). It is favored , particularly by sur-
created by a m isid entification of the anatom y, often facili- geons w ith limited laparoscopic experience, as it often
tated by a “p ercep tu al illu sion” that lead s to erroneou s requires minimal d issection and mobilization of the gall-
assu m p tions abou t the anatom y of the stru ctu res contained bladder prior to controlling the cystic duct. Unfortunately, in
w ithin the triangle of Calot (17). The com m on featu re of the stud y that d escribed the “hid d en cystic d uct synd rome,”
this error in p ercep tion is m isid entification of the com m on 17 of 21 common bile duct injuries w ere sustained when
bile d u ct as the cystic d uct, a mistake also d escribed as the using the infund ibular technique (18). In acute cholecystitis,
“hid d en cystic d u ct” synd rom e that appears to be facili- the cystic d uct is often hid d en behind an inflamed gallblad -
tated by u se of the infu nd ibu lar techniqu e of lap aroscop ic d er neck. Other factors that may contribute to a hidd en cys-
cholecystectom y (18). This error in correctly id entifying the tic d uct includ e large impacted stones, a short or absent
anatom y of the triangle of Calot can lead to w hat is referred cystic d uct, and ad hesions betw een the gallblad d er neck and
to as the “classic” bile d u ct injury (19) clipping and d ivision the comm on d uct, such that the cystic d uct is obscured .
of the com m on bile d u ct, follow ed by fu rther traction on Given these limitations to the infund ibular technique,
the gallblad d er, w hich lead s to a second , higher inju ry w ith many surgeons believe that the “critical view ” technique is
d ivision of the com m on hepatic d u ct, often near the bifu r- the preferred method of laparoscopic cholecystectom y
cation. This second d ivision of the d uct, if noticed by the (10,18,23,24). In this method , the triangle of Calot is com-
operating su rgeon, is often d escribed in the operative note pletely cleared of fibrous and fatty tissues so that only the
as a second cystic d u ct or an accessory d u ct. In som e cases, cystic d uct and artery are visible, as d isplayed in Figure 35.1.
the right hep atic artery is also inju red d u ring this p rocess.
Other d escribed m echanism s of inju ry are listed in
Table 35.1 and include “tenting,” in w hich the common bile
duct is pulled laterally while the cystic d uct is being clipped
and is inad vertently caught in the clip, narrow ing the com-
mon bile d uct; thermal injuries d ue to inappropriate use of
cautery; excessive application of clips to control bleed ing in Gallbladder
Table 3 5 .1 M ech a n ism s of bilia r y in ju r y d u r in g

Cystic artery
la p a roscop ic ch olecyst ect om y
Cystic duct
Misidentification of anatomic structures
• Failure to achieve the critical view of safety
• Common bile duct misidentified as the cystic duct
• Aberrant right hepatic duct mistaken for the cystic duct
• Ligation of right hepatic artery intending to ligate cystic artery
Technical mechanisms
• Inadequately occluded cystic duct FIGURE 35.1. The critical view of safety, created by full dissection of the
structures in the triangle of Calot and mobilization of the infundibulum completely
• Use of cautery too close to portal structures off the cystic plate. Note there are only two structures clearly entering the gall-
• Tenting of cystic duct during dissection and/or application of clips bladder, the cystic duct, and the cystic artery, and the liver is seen clearly
• Overuse of clips to control bleeding through the triangle of Calot. (Reproduced with permission from Greenfield LJ,
• Improper portal dissection Mulholland MW. Greenfield’s surgery: scientific principles and practice, 5th ed.
Philadelphia, PA: Lippincott Williams & Wilkins; 2006: Chapter 60.)
Chapter 35 • Complications of Biliary Surgery 431
To facilitate this dissection and enhance visualization, the Unfortu nately, IOC m ay be p erformed even in cases w here
peritoneum between the liver and the infundibulum is a bile d u ct inju ry is su stained , and the cholangiogram
opened completely. This separates the gallblad d er com- interp reted incorrectly, w hich emp hasizes that its u se is not
pletely from the cystic plate – the adventitial tissue that is equivalent w ith absolute prevention of bile d uct inju ry
opposed to the nonperitonealized portion of the gallblad d er. (17). One stu d y even su ggested that IOC m ay be associated
This allow s the infundibulum to be moved anteriorly and w ith creation of a bile d u ct inju ry in rare cases, occu rring at
posteriorly easily and broadens Calot’s triangle. After this abou t the sam e frequ ency as bile d u ct inju ry in large series
dissection, the cystic plate and surrounding liver should be (0.4%) (34). A p rosp ective trial of rou tine IOC d em on-
visible easily through Calot’s triangle. With this view strated no im p act of the test on the rate of m ajor bile d u ct
achieved, the tw o structures inserting on the gallbladder can inju ry, bu t clearly show ed the increased cost and operative
only be the cystic d uct and cystic artery. If this view is not tim e associated w ith IOC (35–38). A recent analysis of
achieved, the dissection is stopped and a cholangiogram is national patterns of the use of IOC su ggests that it is not
obtained to d efine the anatomy or the proced ure is con- u tilized at all in som e hosp itals p erform ing cholecystec-
verted to open. Reasons that the critical view may not be tom y and is associated w ith m ore than $700 in ad d itional
achieved include aberrant biliary anatomy, such as an absent charges p er case, m aking it not cost-effective to prevent bile
or extremely short cystic d uct, or inflamm ation that obliter- d u ct inju ry (39). More recent stu d ies have questioned the
ates the space between the cystic duct and hepatic duct. Both role of rou tine IOC w hen the critical view techniqu e is
these factors are associated w ith an increased risk of bile em ployed and have argued for the u se of selective IOC in
duct injury and should cause the surgeon to pause and cases w hen the critical view cannot be achieved (23,40,41).
reconsid er the surgical approach. Selective u se of IOC is argu ably the p referred ap p lication
While no d ata from rand om ized clinical trials are avail- of this techniqu e for exp erienced su rgeons, thou gh a com -
able to su p p ort the su p eriority of the critical view tech- p elling argu m ent can be m ad e for su rgeons to rou tinely
niqu e for p revention of bile d uct inju ry, large series d o p erform IOC w hile early in their learning cu rve w ith
sup p ort its safety and efficacy. In a stud y of m ore than 3,000 laparoscopic cholecystectom y and for IOC to be routinely
patients from the N etherland s w ho und erw ent lap aro- tau ght to su rgical trainees. Clearly, it is a technique that all
scop ic cholecystectom y u sing the critical view techniqu e, a su rgeons p erform ing biliary tract p roced u res shou ld be
single bile d u ct inju ry w as noted (for an inju ry rate of able to com p lete efficiently and interp ret accu rately. Ironi-
0.003%) (25). Single-institu tion stud ies w here d ocu m enta- cally, evid ence su ggests that inexp erienced su rgeons and
tion of the techniqu e w as even m ore stringent have con- those in acad em ic p ositions teaching resid ents are exactly
firm ed sim ilar low rates of bile d u ct injury (26,27). The those su rgeons least likely to u se IOC (42).
im portance and sim p licity of the critical view once While the role of IOC in prevention of bile duct injury is
achieved have been increasingly recognized in the su rgical debatable, selective IOC has more clear indications in the
literatu re, and p hoto or vid eo d ocum entation of the critical detection and management of choledocholithiasis. Accepted
view as an essential p ortion of the op erative record has indications for IOC include abnormal liver profile at the time
been ad vocated (24,28,29). of cholecystectomy [elevated aspartate aminotransferase
(AST), alanine aminotransferase (ALT), alkaline phosphatase,
and/ or bilirubin], unsuccessful preoperative endoscopic ret-
■ Use of intraoperative cholangiography rograde cholangiopancreatography (ERCP) for choledo-
The role for intraoperative cholangiography (IOC), and its cholithiasis, and the intraoperative recognition of aberrant
ability to p revent bile d uct injury, has been d ebated since anatomy or suspected injury, as discussed earlier. Other indi-
the introd u ction of the techniqu e. Flum et al. (30) d em on- cations where selective IOC should be strongly considered
strated that not u sing IOC w as associated w ith a higher include a history of biliary pancreatitis without previous
rate of bile d u ct inju ry. After ad ju sting for p atient and su r- ERCP, dilated common bile duct on preoperative imaging
geon covariates, Med icare beneficiaries ap peared 71% that has not been evaluated via ERCP, and a previous history
more likely to sustain a bile d uct injury d u ring cholecystec- of jaundice without ERCP. Some surgeons have advocated for
tom y if IOC w as not perform ed . Based on these com p elling the use of preoperative magnetic resonance cholangiopancre-
d ata and other single-institution series, IOC has been p ro- atography (MRCP), with IOC reserved for patients with
posed as a m ethod to avoid bile d u ct inju ry. Others have abnormal or equivocal MRCP (41,43). MRCP appears to have
su ggested that IOC allow s for the earlier recognition of bile a high correlation with the findings upon performance of IOC
d u ct inju ry w ith lim itation of associated m orbid ity and may prevent the added cost, operative time, and low risk
(14,31,32). In ad d ition, u se of IOC as a m ethod to p revent of biliary injury associated with IOC (44).
bile d u ct inju ry has been su ggested to be cost-effective, as A p otential alternative to IOC is intraoperative u ltra-
prevention of even a single bile d uct injury saves extensive sonography (IOUS). This technique offers the ad vantages of
personal and financial costs for the ind ivid u al patient (33). cholangiography but is noninvasive, repeatable, fast, and
In contrast, other d ata su ggest that IOC m ay not p re- inexpensive. Its limitations are that it is clearly d epend ent
vent bile d u ct inju ry and is not a su bstitu te for carefu l su r- on an experienced u ser, high-resolution equ ipm ent, and a
gical techniqu e, su ch as obtaining the critical view of safety. stand ard and rep rod u cible techniqu e. Su rgical trainees are
not rou tinely tau ght IOUS, and m any of their sup eriors
may not have incorp orated it in their p ractice, therefore
lim iting the p rop agation of the techniqu e. N evertheless,
com parative series suggest that in experienced hand s,
IOUS offers equ ivalent or su p erior sensitivity and sp eci-
ficity in the d etection of com m on bile d uct stones to IOC,
w ith no increased risk of bile d u ct inju ry (45–49). IOUS
may eventually replace the use of IOC for m any ind ications
(50), akin to the transition that has occu rred aw ay from A B
ERCP tow ard initial end oscopic ultrasou nd (EUS) for eval-
uation for d istal biliary obstru ction.
■ Diagnosis of bile duct injury following

cholecystectomy
Intraoperative Diagnosis of Bile Duct Injury
C D
Recognition of a biliary inju ry d u ring cholecystectom y can
be a d istressing scenario for any su rgeon. As d escribed ear-
lier, m ost biliary inju ries are the resu lt of a m isp ercep tion of
anatom y that p ersists until the inju ry is recognized , so su r-
geons w ho find them selves in this situation are often sur-
prised , as w ell as fearfu l of the m orbid ity that their p atients E1 E2
may su ffer. Even exp erienced surgeons should call a col- >2 cm <2 cm
leagu e into the operating room for assistance and cou nsel.
Even if a hep atobiliary surgeon is not available, a second E3
su rgeon w ith a new p ersp ective and m ore objectivity abou t
the ind ivid u al case can assist greatly in intraop erative d eci-
sion-m aking and su rgical m anagem ent. As soon as a bile
d u ct inju ry is su sp ected , an IOC should be perform ed .
Dep end ing on the p oint in the cholecystectom y w hen the
injury w as recognized , cannu lation of a d uctal stru ctu re
may be d ifficu lt and itself requires conversion to a laparo-
tom y. Inability to p erform a cholangiogram and confu sion E4 E5
abou t the anatom y shou ld alw ays prom pt conversion to a
laparotom y. In the rare case w here a bile d u ct injury is rec- FIGURE 35.2. The Bismuth–Strasberg classification of biliary injuries fol-
lowing laparoscopic cholecystectomy. (Reproduced with permission from
ognized and confirm ed by IOC w hile still lap aroscop ic and
Winslow ER, Fialkowski EA, Linehan DC, et al. “Sideways”: results of repair of
the p rim ary su rgeon is not com fortable p erform ing the biliary injuries using a policy of side-to-side hepatico-jejunostomy. Ann Surg
repair, lap aroscop ic p lacem ent of subhepatic d rains w ith 2009;249(3):426–434.)
im m ed iate transfer to a hepatobiliary surgeon and center is
app rop riate.
Once IOC confirm s a bile d u ct inju ry, attention need s to is not going to occu r at the ind ex op eration. IOUS w ith liver
be paid to the cond ition of the patient and the extent of the d u p lex exam ination can be qu ite help fu l in d ocu m enting
inju ry. Bile d u ct inju ries can occur in the setting of a lengthy hepatic arterial and portal venous inflow to both lobes of
or d ifficult d issection, so consid eration of the patient’s anes- the liver, w hich can offer d elineation of the d egree and sig-
thetic cou rse, control of bleed ing, and d egree of resu scita- nificance of any associated vascu lar inju ry.
tion shou ld be d iscu ssed . If the d ecision is m ad e to rep air The d ecision to proceed w ith repair of a biliary injury at
the inju ry at the tim e of the ind ex operation, the anesthetic the primary operation should be mad e carefully. Stud ies
and op erative staff should be alerted of the need for ad d i- have d ocum ented that one of the risk factors for p oor out-
tional op erative tim e and any ad d itional equ ip m ent that comes follow ing repair of a bile d uct injury follow ing chole-
may be need ed (retractors, biliary catheters, fine su tu res, cystectom y is rep air by the p rimary su rgeon (11,51,52),
instru m ents, etc.). Once the patient’s stability is assu red , w hich reflects not only the lack of ad vanced hepatobiliary
the su rgeon shou ld tu rn to carefu lly and m ethod ically exp erience am ong m ost su rgeons p erform ing lap aroscop ic
d efining the classification of the biliary inju ry (see Fig. 35.2) cholecystectom y bu t also the ju d gm ent and insight that
and assessing for any associated vascular injury. Ad d i- m ay be com p rom ised by the em otions of a recognized
tional d issection may be need ed to d efine the portal struc- inju ry. Su rgeon exp erience is not the only consid eration, as
tures, but this should be d one cautiously, especially if repair thou ght shou ld be given to the availability of resou rces
that may be necessary in the postoperative period to assist the liver p rofile m ay be su btle—total biliru bin m ay be nor-
in management of these complicated patients, includ ing but mal or only slightly elevated (2 to 4 m g/ d L) in the case of a
not lim ited to intensive care resou rces, ad vanced end o- com p lete biliary transaction w ith free leak. Reabsorption of
scopists, and interventional rad iology. Technical factors bile from the p eritoneu m m ay elevate the biliru bin slightly.
related to the inju ry should also be consid ered . Inju ries that Marked elevation of the AST and ALT is u su ally not p res-
involve the hepatic d uct bifu rcation or higher, inju ries w ith ent and shou ld raise concern of an associated vascular
associated vascu lar compromise, and biliary inju ries mad e inju ry w hen p resent. Biliary inju ries are typ ically not asso-
w ith thermal energy (as opposed to sharp d issection) ciated w ith significant abnorm alities of the am ylase and
should all be consid ered relative contraind ications to repair lip ase. When these valu es are elevated follow ing cholecys-
at the primary operation either d ue to their complexity tectom y, esp ecially in concert w ith an abnorm al liver pro-
(high or segmental d uctal injuries) or d ue to the possibility file, a retained com m on bile d u ct stone rather than a bile
of the injury evolving further (in the case of thermal injuries d u ct inju ry m ay be the p roblem .
and those w ith associated hep atic arterial ligation). One A heightened aw areness of bile d u ct injury shou ld be
final consid eration is that most hepatobiliary su rgeons p re- maintained in all patients w ith early problem s follow ing
fer to encounter these injuries in as und isturbed a field as cholecystectom y, w ith efforts m ad e to confirm or refu te
possible, w here they can gu id e the ad d itional d issection, that d iagnosis m ad e efficiently. Postcholecystectom y pain
and the results of repair are clearly better than w hen having that ap p ears ou t of p rop ortion to the u su al p ain follow ing a
to red o a previous repair. It is better to d ecid e early to refer lap aroscop ic p roced u re, or p resents in a d elayed fashion
the patient to a hepatobiliary surgeon than to make that after the initial p ostop erative d iscom fort has resolved ,
d ecision after having attempted a suboptimal repair. d eserves a thorou gh investigation. A carefu l interval his-
If the d ecision is m ad e not to rep air the inju ry at the p ri- tory and p hysical exam , and laboratory stu d ies as ind i-
mary op eration, d rains shou ld be placed and arrangem ents cated , are im p ortant. Mistakes m ay be m ad e w hen
mad e for im m ed iate transfer to a hepatobiliary center. In managing su ch p atients over the p hone, or through
the case of a comp lete transaction w ith ligation, it is not mid level p rovid ers, w hen a clinic visit often is all that is
necessary to “u nd o” the ligation. Rem oving su tu res and need ed to d istingu ish incisional pain or abd om inal w all
clip s can be d ifficult and associated w ith bleed ing, w hich bru ising from a m ore seriou s p roblem. Initial focu s shou ld
then requ ires ad d itional m aneuvers to control. Leaving the be on the ap p rop riate resu scitation and stabilization of the
biliary system obstructed in the short term d oes not typ i- p atient, as both cholangitis and infected extravasated bile
cally cau se im m ed iate morbid ity and m ay even facilitate can lead to p rofou nd sep sis (54,55). Broad sp ectru m antibi-
the p lacem ent of transhep atic catheters if the biliary system otics shou ld be ad m inistered efficiently if either of these
d ilates p roxim ally. If the hepatic d uct is open and d raining, d iagnoses are su sp ected or confirm ed .
a red ru bber catheter or silastic feed ing tu be m ay be p laced Initial diagnostic imaging may include ultrasound, to
into the proxim al d u ct in an effort to control the biliary out- assess for perihepatic fluid collections and biliary ductal
flow. Again, excessive m aneuvers to su tu re in a tu be, p lace d ilatation, or computed tomography (CT) in select patients.
a balloon catheter, or other involved means to control bil- If id entified , significant perihepatic collections m ay be per-
iary d rainage are w ell intend ed but m ay be associated w ith cutaneously d rained . If bilious, a biliary leak is d iagnosed
fu rther inju ry to the rem nant d u ct, w hich potentially short- and the evaluation should proceed w ith d irect cholangiogra-
ens the am ount of hepatic d uct available to the repairing phy either by ERCP or by percutaneous transhepatic cholan-
surgeon (53). Leaving large (10 French or greater) su bhep - giography (PTC). If the fluid visualized on ultrasound or CT
atic biliary d rains is often perfectly ad equ ate to control bil- is not easily drained, or if the question of a biliary injury is
iary efflu ent for the tim e of transfer until d efinitive repair still open, a hepatobiliary im ino-d iacetic acid (H IDA) scan
or d rainage can be achieved . may be performed . H IDA scans can d etect extravasation of
biliary d rainage and may also demonstrate failure of bile
Postoperative Diagnosis of Biliary Injury excreted from the liver to enter the d uodenum. Further
Bile d uct inju ries follow ing cholecystectomy can present in anatomic detail is not available from HIDA scans, but it may
an early or late m anner, and the severity of their p resenta- be sufficient to confirm a suspicion of biliary injury before
tion is often d ep end ent on the d egree of inju ry. Early sym p - proceed ing to more invasive means of cholangiography. CT
tom s that shou ld p rom p t fu rther evalu ation inclu d e fever, angiography, w ith dual arterial and portal venous phases,
nau sea, em esis, abd om inal pain, and m alaise. Biliou s can be used to d efine associated vascular injury.
d rainage from a surgical d rain or from an incision is alw ays ERCP by a skilled end oscop ist is often the best initial
abnorm al and d iagnostic of a biliary leak. Even in the case invasive stud y in a patient w ith a su spected biliary inju ry.
of inju ries associated w ith com p lete ligation of the extra- In inju ries w here the connection of the extrahep atic biliary
hep atic biliary d rainage, jaund ice m ay not occu r as abd om - tree to the d uod enum is still intact, ERCP may be d iagnostic
inal pain and other sym ptom s w ill often lead patients to and therapeutic. Endoscopic sphincterotomy and placement
seek care before their biliru bin has had tim e to rise signifi- of an end obiliary stent are often sufficient to treat biliary
cantly. Laboratory evaluation may be und erw helm ing, leaks from the cystic duct stump or small accessory d ucts.
thou gh a leu kocytosis m ay be p resent. The abnorm alities of Incom p lete transection s m ay be brid ged by end obiliary
stents, w ith the need for subsequent operative intervention incid entally, either by a m ild ly abnormal liver p rofile on
determined over time. In cases of common bile duct ligation, rou tine laboratories or w ith segm ental d u ctal d ilatation or
or in instances w here a segment of the extrahepatic d uct is atrop hy on imaging. Biliary strictu re is typ ically the etiol-
excised w ith the gallbladder leaving an open proximal and ogy of all these d elayed p resentations of occu lt bile d u ct
distal extrahepatic bile duct, ERCP may not be ad equate to inju ry d u ring cholecystectom y, thou gh rare d elayed leaks
provide anatomic detail of the proximal biliary tree, nor be w ith contained bilom as or biliary fistu las m ay occu r (54). In
able to facilitate crossing the injury. In these cases, percuta- these cases, the evalu ation of the p atient typ ically proceed s
neous transhepatic cholangiogram (PTC) w ith placem ent more m ethod ically in a su bacu te or elective fashion,
of transhep atic biliary d rains is typ ically necessary. althou gh the d evelop m ent of cholangitis may requ ire m ore
PTC in a p atient w ith a d ecom pressed biliary system is u rgent p roced u res to im p rove biliary d rainage. MRI w ith
very d ifficu lt and requ ires sop histicated interventional MRCP can be a very inform ative stu d y in these p atients, as
rad iology resou rces and expertise. It is not u ncom m on for it gives excellent segm ental biliary anatom y as w ell as the
these p roced u res to take rep eated attem p ts at access and op p ortu nity to investigate associated vascu lar inju ries.
then ad vancem ent of transhep atic catheters over a series of MRCP has the ad vantage of d elineating exclu d ed biliary
d ays. It is often necessary to place ad d itional percutaneou s segm ents that m ay not be ap p arent by ERCP or PTC.
d rains to control bile leakage and d rain infected bilomas MRCP thu s often facilitates d ecision-making abou t w hat
until the biliary d rainage is ad equ ately d iverted . These rou te is m ost ap p rop riate for d irect cholangiograp hy.
patients tru ly requ ire m u ltid isciplinary m anagem ent to
ensure that proced ures are coord inated w ith the goals of Classification of Bile Duct Injury
im proving the p atient’s cond ition, d efining the relevant Effective management of biliary injury follow ing cholecys-
anatom y, and facilitating eventual d efinitive rep air. For this tectom y relies u pon und erstand ing of the anatom ic d etails
reason, the hep atobiliary surgeon need s to be involved in of the inju red biliary tract and applying the appropriate per-
all d ecisions abou t p lacem ent of d rains and transhep atic cu taneou s, end oscopic, and su rgical interventions catered
catheters and the tim ing of these p roced ures. to the severity of inju ry. To assist w ith these d ecisions and to
As w ith any su rgical proced ure, associated injuries from p rovid e accu rate communication among p rovid ers, the Bis-
electrocautery, lysis of ad hesions, or passing of instruments muth–Strasberg classification system has been ad opted
to the bow el or solid organs should be consid ered . Wound (Fig. 35.2) (10). These injuries vary in their presentation and
com plications, though u ncom m on follow ing laparoscop ic require specific consid erations in their d iagnosis.
cholecystectom y, shou ld be m anaged ap propriately. Bleed - Type A—Type A inju ries present as a bile leak, either from
ing com plications after cholecystectom y are fortu nately the cystic d uct stu m p or from sm all accessory d ucts in
rare, bu t can be seen m ore com monly in patients on sys- the cystic p late (d u cts of Luschka). The extrahepatic bil-
tem ic anticoagu lation, patients w ith chronic liver d isease, iary system is intact and not com prom ised . These
or p atients w ith throm bocytop enia d u e to hematologic d is- inju ries typ ically p resent in the first w eek after su rgery,
ease. One clinical scenario that d oes arise occasionally is althou gh they have been reported as late as 2 to 3 w eeks
the p ostcholecystectom y p atient w ith abd om inal p ain w ho postoperatively. They are rarely d iscovered intraopera-
is found to have a collection in the form er gall blad d er tively. Patients present w ith signs and sym ptom s of a bil-
fossa. These collections d o not typ ically need sp ecific iary leak or bilom a, w ith abd om inal p ain, fever, anorexia,
intervention, thou gh m ay need fu rther evalu ation p rim a- and nausea. Jau nd ice is rare, thou gh mild hyperbiliru -
rily to d eterm ine w hether or not they contain bile and thu s binemia in the range of 2 to 3 mg/ d L may occur d u e to
rep resent the m anifestation of a biliary inju ry. If no biliary absorp tion of bile from the peritoneum. Cystic d u ct
leak is d em onstrated by H IDA and / or cholangiogram , stump leaks may occur d ue to inaccurate clip placement,
gall blad d er fossa flu id collections d o not u su ally requ ire perforation p roximal to the clip, cystic d uct necrosis, or
d rainage. H em atom as shou ld p referably not be instru - clip d islod gment d ue to increased intrad uctal pressure
m ented and w ill resolve over time. Infected fluid collec- second ary to a retained common bile d uct stone. These
tions are unusual, but can occur in the context of acute or leaks are often read ily d em onstrated by ERCP. Accessory
gangrenou s cholecystitis (56) or as a consequence of spilled d uct leaks are d istinct from the aberrant segmental d uct
stones at the time of cholecystectomy (57,58). Image-guid ed inju ries classified as Type B or C, as accessory leaks
percu taneou s d rainage is typically ad equ ate in su ch cases to im p ly that they are not the only rou te of biliary d rainage
d istinguish a subhepatic abscess from a biloma and resolve for the involved liver segment. These leaks may be of rel-
any associated septic complications. atively low volu me and sometimes hard to see on ERCP.
Late p resentations of bile d uct injury m ay be m ore su b- They may present as a biloma w ithout significant ongo-
tle. Stu d ies from large referral centers su ggest that u p to ing d em onstrated leak. Type A inju ries are the m ost com -
50% of biliary inju ries not recognized in the operating room mon bile d uct injuries follow ing cholecystectomy, w ith
w ill p resent in a d elayed fashion (i.e., 30 d ays postop era- the vast m ajority being cystic d u ct stum p leaks (10).
tively) (54,59,60). Patients m ay p resent w ith jaund ice and Type B—Type B injuries are defined as ligation and division
abd om inal p ain, or cholangitis m ay be the initial present- of an aberrant segmental hepatic d uct, typically the d uct
ing sym p tom . Som e segmental injuries m ay be d iagnosed d raining the right posterior section (segments 6 and 7) or
the segmental d uct to segment 6 alone. This injury is often Type E1: Circu m ferential inju ry to the com m on d u ct 2 cm
facilitated by the associated anomaly w here the cystic from the bifu rcation.
d uct d rains into this aberrant right posterior d uct, an Type E2: Circu m ferential inju ry to the com m on d u ct 2 cm
anatomic variant well described by Couinaud (61). The from the bifu rcation.
proximal and distal end s of the aberrant duct are clipped Type E3: Circu m ferential inju ry to the com m on d uct at the
and divided during control of the cystic duct. Type B bifu rcation.
injuries are often asymptomatic or present late with Type E4: Inju ry to the right or left hep atic d u ct.
abd ominal pain or cholangitis involving the occluded Type E5: Com bined inju ry to the com m on d u ct and an aber-
liver segment. N ormally, the liver behind a Type B injury rant right hep atic d u ct.
w ill atrophy and the remaining liver w ill hypertrophy.
The m ajority of Type E injuries w ill requ ire PTC to
Type C—Type C injuries are d efined as d ivision of an aber-
d efinitively reveal the anatom ic d etails of the injury and to
rant right posterior segmental d uct w ithout ligation.
establish stable biliary d rainage.
They arise d ue to the same anatomic variant as Type B
injuries but vary in their presentation as they cause
spillage of bile into the peritoneal cavity w ith the d evel- ■ Management of bile duct injury
opm ent of bile peritonitis or a biloma. Their initial presen-
Bile d u ct inju ries may be d iverse in their p resentation, and
tation may be very similar to Type A injuries, and it w ill
the m anagem ent should alw ays be catered to the patient’s
often appear on initial cholangiogram s that the entire bil-
clinical cond ition and the anatom ic d etails of the inju ry.
iary system is intact. Careful inspection of a good-quality
Principles that apply in all cases inclu d e control of sepsis,
ERCP w ill allow detection of the lack of filling of the pos-
d rainage of all bile collections, and establishm ent of secu re
terior segment(s). PTC may also miss this injury if either
biliary d rainage. Vigilant reassessm ent of the patient’s clin-
the left d uctal or right anterior system is entered . Persis-
ical cond ition, w ith frequ ent reim aging to d etect u nd rained
tent biliary leak in the presence of an intact cystic d uct lig-
sou rces of intraabd om inal sep sis, w ill get even the frailest
ature should prompt investigation for a Type C injury.
p atients throu gh w hat can be tenu ou s early stages of their
Injection into a subhepatic biloma d rain (d rain sinogram )
inju ry, allow ing d efinitive rep air to be p erform ed typically
may opacify the transected and leaking segmental d uct.
in an elective fashion on a healthy p atient. Tim ing of d efin-
PTC via the right posterior segment can confirm the diag-
itive rep air for those p atients w ho requ ire biliary recon-
nosis and gain control of the biliary fistula.
stru ction is an ind ivid ualized d ecision that requires carefu l
Type D—Typ e D inju ries are d efined as lateral inju ry, typ i-
su rgical ju d gm ent and p atience. While p ressu re m ay exist
cal incom p lete transaction or cau tery inju ry, to an extra-
from the p atient, the p atient’s fam ily, referring physicians,
hep atic bile d u ct. As in Typ e A injuries, all hep atic
and colleagu es to get the p atient to the op erating room
segm ents rem ain in continu ity w ith the d istal biliary
soon after inju ry, it is critically im p ortant that the patient be
tree and d u od enu m , thou gh the severity of the leak m ay
p hysiologically appropriate for w hat can be a prolonged
be significant d epend ing on the size and location of the
op eration and recovery p eriod and that the su rgeon has a
inju ry. These inju ries m ay be generated in protean w ays,
fu ll u nd erstand ing of the d egree of the p atient’s inju ry.
inclu d ing sharp lateral injury d uring d issection, therm al
Once biliary d rainage is established and infection is con-
injury to the lateral asp ect of the right or com m on
trolled , there is no need to ru sh, and these repairs can be
hep atic d u ct d uring d issection, or partial occlu sion or
qu ite straightforw ard w hen p erform ed in an elective fash-
laceration of a hepatic d u ct d uring clip placem ent. These
ion after acu te inflam mation su bsid es.
inju ries m ay present early, w ith bile leak and sep sis.
As w ith their d iagnosis and p resentation, m anagem ent
H ow ever, Typ e D inju ries d u e to therm al trau m a or clip
of bile d u ct inju ries can be d erived from their Strasberg
p lacem ent m ay present late w ith the d evelopm ent of a
classification.
biliary strictu re w ithout extravasation of bile. Given
their central natu re, Type D injuries are read ily seen on Type A—Typ e A inju ries can typ ically be ad d ressed d efini-
ERCP or PTC. tively w ith percutaneou s d rainage of bile collections and
Type E—Type E injuries are d efined by complete d isruption end oscopic therapy. End oscopic sphincterotom y w ill
of biliary–enteric continuity d ue to transection, excision, d ecompress the d istal biliary tree, allow ing d iversion of
and/ or ligation of the extrahepatic biliary tree. Injuries bile aw ay from the leaking cystic d uct stu mp or acces-
that includ e a free biliary leak w ill present early w ith bile sory hepatic d uct. Placement of an end obiliary stent is
peritonitis and sepsis. Injuries with occlusion of the prox- typically perform ed at this proced ure and w ill u su ally
imal hepatic drainage may present in a delayed fashion promp tly stop any ongoing leak. ERCP has the ad d i-
w ith jaund ice and / or cholangitis, although still typically tional ad vantage of surveying the bile d u ct for choled o-
w ithin 2 w eeks of cholecystectomy as all biliary d rainage cholithiasis, w hich may be associated w ith Type A biliary
is blocked . Typ e E inju ries are fu rther su bclassified leaks (62). Rem oval of the stent in 4 to 6 w eeks is usu ally
accord ing to the Bismuth classification, with important all that is required in this setting. As the extrahepatic bil-
implications about the complexity of establishing biliary iary d rainage w as not d irectly com prom ised , the risk of
d rainage and obtaining ultimate definitive repair. subsequent stricture or associated problem is minimal.
Type B—Typ e B inju ries m ay not require specific interven- collections is typ ically necessary to alleviate sym p tom s
tion, esp ecially w hen the inju ry is d iagnosed late in and control infection. While it m ay be p ossible to restore
patients w ithou t cholangitis. If significant atrophy of the biliary continu ity via p lacement of a p ercu taneous bil-
affected segm ent(s) has alread y occu rred , or the seg- iary catheter, the risk of strictu re across the healed inju ry
m ent(s) involved is(are) sm all in volu m e, the valu e of an is high. In the acu te setting, exp erts have recom m end ed
intervention is p robably low. In fact, instrum enting the ligation of sm all segm ental d u cts 2 m m, bu t this is an
occlu d ed segm ent(s) is(are) inevitably associated w ith op tion only in d u cts that have not been instru m ented
the introd u ction of bacteria and su bsequ ent risk of d u e to the risk of cholangitis. Therefore, ap prop riate
cholangitis. In p atients w ho are sym ptom atic, access to op tions inclu d e segm ental Rou x-en-Y hep aticojeju nos-
the affected segm ent(s) is perform ed via PTC. If the tom y, or hep atic resection. H ep atic resection m ay be
involved segmental d u ct m ay be id entified and is 2 to m ost ap p rop riate w ith a sm all involved segm ental d u ct,
3 m m , it can be reconstructed w ith a Rou x-en-Y hep ati- esp ecially w hen the stricture or injury is at or above the
cojeju nostom y. An ind w elling PTC catheter at the tim e p ortal p late or p reviou s attem p ts at rep air have failed
of su rgery can be help fu l in locating the involved d u ct (Fig. 35.3) (23).
and m ay be p laced across the anastom osis to lessen the Type D—Typ e D inju ries m ay be d iagnosed either intraop-
risk of p ostop erative leak. A follow -u p cholangiogram eratively or in the early or late postoperative period .
at 3 to 6 w eeks p ostop eratively m ay be perform ed w ith When recognized intraop eratively, the extent and m ech-
rem oval of the biliary catheter if the segm ental d rainage anism (sharp vs. therm al) m u st be consid ered in choos-
is ap p rop riate. In cases w here reconstruction of a sm all ing the ap p rop riate rep air. A tru e p artial transection
segm ental biliary d uct is not possible, hep atic resection p erformed sharp ly is likely the only reasonable ind ica-
of the involved segment(s) w ill elim inate the p roblem of tion for a prim ary repair in the setting of bile d u ct inju ry
cholangitis and segm ental biliary stasis. Outcom es from d u ring cholecystectom y. Placement of a T-tu be, either
reconstru ction of right segmental hepatic d u cts are throu gh the injury or via a separate choled ochotom y,
noted to be less d u rable than rep airs of larger d u cts, w ou ld be the classic m ethod for rep airing this typ e of
w ith m ore frequ ent need for repeat intervention (63). p artial inju ry. In the case of larger inju ries, or injuries
Type C—Typ e C inju ries m ay be m anaged exactly like Typ e su stained w ith a therm al m echanism w ith d evitalized
B inju ries, althou gh in a m ore urgent fashion d u e to the tissu e, it m ay be necessary to d ebrid e back the d uct to
associated biliary leak. Access to the involved segm ental healthy tissu e. A p rim ary end to end rep air either over
d u ct m ay be d ifficu lt and m ay requ ire atyp ical m ethod s an internal catheter p laced across the am p u lla (such as
su ch as op acifying the involved segm ental biliary rad i- an end obiliary stent, d ou ble J u reteral stent, or trim m ed
cles by injection of a bilom a d rain or a com bined silastic p ed iatric feed ing tu be) or a T-tu be m ay be p er-
ERCP–PTC “rend ezvous” p roced ure to facilitate p lace- form ed . Unfortu nately, w hat d ata exist abou t prim ary
m ent of a p ercu taneou s biliary catheter across the inju ry bile d u ct rep air su ggests a high rate of early failure and a
(64). As in Typ e A inju ries, percu taneous d rainage of bile strictu re rate of u p to 50% typ ically requ iring a fu tu re
A B C
FIGURE 35.3. Type C biliary injury. The patient, a 33-year-old woman, developed bile peritonitis following a laparoscopic cholecystec-
tomy. Percutaneous drains were placed, but the source of the leak was erroneously assumed to be cystic duct stump leak. She eventu-
ally developed abdominal pain and fever; magnetic resonance cholangiopancreatography (Panel A) revealed a disruption between her
aberrant right posterior hepatic duct (RPHD) and common bile duct (CBD). This disruption and subsequent stricture were studied further
with percutaneous transhepatic cholangiography (Panel B) and eventually dilated. However, the stricture recurred as documented by
endoscopic retrograde cholangiopancreatography (Panel C), and the patient suffered recurrent bouts of cholangitis. She was eventually
treated with a laparoscopic liver resection of segments 6 and 7 and is now clinically well.
revision (51). Thu s, in cases w here the injury ap p ears ad vised , p articu larly if there is a su bstantial biliary leak
more su bstantial, either d ue to involvem ent of m ore w ith associated p erihep atic inflam m ation and staining.
than half the d u ctal circu m ference or d u e to associated
tissu e d evitalization, or in cases w ith associated vascu - In p atients w ho p resent beyond 72 hou rs from their
lar inju ry, Roux-en-Y hepaticojejunostom y to healthy inju ry and have ongoing sepsis and / or a poorly managed
d u ctal tissu e above the injury shou ld be p erform ed . biliary leak, initial interventions shou ld be focu sed at
Type E—Managem ent of Type E injuries requires com m and d raining bile collections and establishing control of biliary
of a sp ectru m of hep atobiliary su rgical techniqu es and d rainage. This rarely if ever shou ld requ ire op erative inter-
exp ertise (11,51,52). Repairs are typically d one at or vention and can be accom plished by a combination of per-
above the level of the hepatic d u ct bifu rcation, w ith d iscu taneou s and end oscop ic m eans. Som e hepatobiliary
section into the p ortal p late necessary for exp osu re. su rgeons ad vocate an attem p t at ERCP for d elineation and
Decisions abou t the tim ing and techniqu e for the rep air control of the inju ry, before m oving to a p ercu taneous tran-
requ ires a fu ll u nd erstand ing of the anatom y involved , shep atic ap p roach (60). H ow ever, the m ajority of injuries
and thu s p roceed ing w ith im m ed iate rep air shou ld be w ill requ ire transhep atic control from above the level of the
d one cau tiou sly. In the situ ation w here an exp erienced inju ry, an ap p roach that p rom p tly controls the biliary ou t-
su rgeon is available at the tim e of inju ry or a p atient is p u t and facilitates the eventu al rep air (20,54,55). In rare
transferred im m ed iately after intraop erative recognition cases w here the extrahep atic biliary tree is p artially intact
of an inju ry, early rep air has been show n to be safe w ith or at least the p roxim al and d istal end s of the inju ry are
accep table long-term ou tcom es (54,59,60). In the case of ad jacent to each other, a com bined end oscopic and tran-
p atients transferred early after their injury, the qu estion shep atic ap p roach can be u sed to bring a biliary catheter
of w hen is too late to attem p t im m ed iate rep air is con- across the inju ry into the d u od enu m (65–68). In rare cases,
troversial. Patients m u st be physiologically w ell w ithou t p articu larly in p atients w ith com orbid d isease that d elays
evid ence of intraabd om inal sepsis and shou ld not have or p revents d efinitive rep air, this rend ezvou s approach
evid ence of significant liver inju ry, suggesting associ- m ay p rove to facilitate healing of the inju ry over the p ercu -
ated vascu lar inju ry, and the extent of the inju ry shou ld taneou s catheter (Fig. 35.4).
be u nd erstood either from IOC and d iscu ssion w ith the The preferred m ethod for repairing m ost injuries is a
p rim ary su rgeon or via p reoperative cholangiograp hy. Rou x-en-Y hep aticojeju nostom y, and the key principles
Rep air beyond 72 hours from injury is probably ill- inclu d e creation of a tension-free anastom osis to healthy
A B
FIGURE 35.4. Type E2 biliary injury managed with combined endoscopic retrograde cholangiopancreatography–percutaneous tran-
shepatic cholangiography (ERCP–PTC) “rendezvous” procedure. Panel A displays PTC images of a large volume biliary leak from an
injury within 2 cm of the hepatic duct bifurcation, with no visible filling of the distal common bile duct. ERCP was performed introducing a
wire into the subhepatic space through the transected distal common bile duct. The wire was snared via the transhepatic catheter,
allowing introduction of bilateral percutaneous biliary catheters across this complex injury, as seen in Panel B. This biliary injury was
managed with the percutaneous catheters alone; the biliary leak sealed and the tubes were left in place.
hep atic d u cts that d rain all biliary segm ents. Stew art and w ith Typ e E inju ries. Care shou ld be taken to choose a part
Way analyzed the treatm ent of 88 patients w ho su stained a of the p roximal jeju nu m that reaches easily to the right
major bile d u ct injury d u ring lap aroscopic cholecystec- u p p er qu ad rant. In p atients w ith p reviou s abd om inal su r-
tom y (51). Fou r factors w ere fou nd to play a m ajor role in gery, tim e shou ld be taken to m eticu lou sly lyse any ad he-
the su ccess or failu re of treatm ent: p erform ance of p reop er- sions that tether the sm all bow el m esentery. In cases w here
ative cholangiograp hy in ord er to d efine the site of inju ry p atients have a foreshortened m esentery, either d u e to pre-
and biliary anatom y, the choice of surgical repair, d etails of viou s su rgery, rad iation or d u e to other cond itions, a
the operative techniqu e, and the experience of the surgeon med ial visceral rotation of the right colon w ill exp ose the
perform ing the rep air. The im portance of d elineation of the root of the sm all bow el m esentery that can be m obilized u p
biliary anatom y p reoperatively is clear: 96% of proced u res to the level of the d u od enu m and neck of the p ancreas. The
that w ere p erform ed in w hich cholangiogram s w ere not sm all bow el shou ld be d ivid ed at an ap p rop riate p lace
obtained p rior to su rgery w ere not successful and 69% of w ith a stap ler, and the m esentery shou ld be d ivid ed to
the p roced u res in w hich the cholangiograp hic d ata w as allow the Rou x lim b m axim u m m obility. Division of the
incom p lete p rior to operation w ere u nsuccessfu l. In con- first vascu lar arcad e of the sm all bow el m esentery can usu-
trast, w ith p reop erative cholangiographic d ata, rep airs ally be d one safely, thou gh the end of the Rou x lim b shou ld
w ere su ccessfu l in 84% of cases (51). This stu d y and others alw ays be insp ected for su fficient p erfu sion. A retrocolic
d ocum ented the inad equacy of prim ary repair for these Rou x-en-Y hep aticojeju nostom y, brou ght to the right u pper
high Typ e E injuries; a prim ary end -to-end d u ctal rep air qu ad rant through a d efect m ad e in the m esocolon to the
w as never su ccessfu l w hen there w as a com p lete bile d u ct right of the m id d le colic vessels and above the d u od enu m ,
transection (51,52). p rovid es the m ost d irect rou te to the p orta and can avoid
The necessity of transhep atic biliary stents for rep air any u nd u e tension created by d rap ing the Rou x lim b over
of Typ e E inju ries has been d ebated am ong hep atobiliary the colon.
su rgeons (19,23,54,55,69). Clearly obtaining PTC p reop - A few im p ortant p rincip les ap p ly to the d issection of
eratively can offer anatom ic d etail that m ay be d ifficu lt to the p orta in these com p lex Typ e E inju ries. The m echanism
d eterm ine in traop eratively d u e to associated inju ry and of bile d u ct inju ry in these cases often arises from u ninten-
the challenges of IOC in high d u ctal inju ries. If PTC tional d issection of a long segm ent of the bile d u ct, w hich
access can be established , m any su rgeon s an d interven - can strip the d u ct of its blood su p p ly, w hich ru ns throu gh
tional rad iologists argu e that a stent shou ld be p laced the p erid u ctal ad ventitial tissu e. In early rep air cases, it is
an d u sed as a brid ge across the eventu al hep aticojeju nos- therefore im p ortant to id entify a p ortion of the d u ct that
tom y. Clearly, in the setting of a p atient not u nd ergoing has not been com pletely d issected and carefu lly expose or
an early d efin itive rep air, tran shep atic biliary stents are shorten the hep atic d u ct in a location that is am enable to
necessary for m ain ten an ce of biliary d rain age an d can be constru ction of the biliary anastomosis. In Typ e E1 or E2
u sed d u ring the eventu al rep air to assist in id entification inju ries, it m ay be p ossible therefore to stay below the tru e
of the d u ctal anatom y and for tem p orary stenting of the hep atic d u ct bifu rcation, bu t care shou ld be taken not to
hep aticojeju n ostom y. Large series d escribe the u se of sew to a trau m atized end of the hep atic d u ct. Op ening the
transhep atic stents for as long as 12 m onths after d efini- d u ct on its anterior su rface, w ith a d u ctotom y extend ed
tive rep air, allow in g access for cholangiograp hy and p er- tow ard the long extrahep atic p ortion of the left hep atic
cu taneou s interventions su ch as anastom otic d ilatation d u ct, can exp ose healthy tissu e, hold su tu re, and avoid fu r-
w h en n ecessary (55,70). H ow ever, recen t tren d s su ggest ther d issection behind the d u ct, w hich can fu rther com pro-
that these catheters can be rem oved early in the p ostop er- mise d u ctal blood su p p ly. In later rep air cases, avoid ing
ative p eriod if n o anastom otic com p lication s are su s- d issection behind the hep atic d u ct is really essential, as this
p ected (54,60,69). allow s p reservation of any collateralized blood su p ply that
The u tility of transhep atic stents in early rep airs is less has been created at the site of the inju ry. This p rincip le of
w ell d efined . H istorically, silastic catheters w ere placed ret- “anterior-only” d issection also avoid s creating ad d itional
rograd e over Bakes d ilators or other instru m ents p assed vascu lar inju ry, as the right hep atic artery is often d irectly
ou t of the d u ctal system and throu gh the hep atic behind the hep atic d u ct at this level and can be obscu red or
parenchym a (21,71). This techniqu e is not in the arm am en- d ifficu lt to id entify in a chronically inflam ed or scarred
tarium of m ost active hep atobiliary su rgeons, and these field .
catheters are far m ore com m only placed percutaneou sly in For Typ e E3 inju ries or high er, the hep atic d u ct bifu r-
mod ern p ractice. Given the potential d ifficulty in p lacing cation need s to be exp osed , by low ering the p ortal p late.
percutaneou s transhepatic catheters into a d ecom p ressed This involves incising into the liver p arenchym a to get
biliary system after an early recognized bile d uct inju ry above the hep atic d u ct bifu rcation, begin nin g above th e
(and therefore the potential d elays im plied ), som e su r- left hep atic d u ct in the techniqu e d escribed by H ep p and
geons w ill go to the operating room w ithou t a transhepatic Cou inau d (Fig. 35.5) (72). This can often be d one w ith a
catheter if the d ecision is m ad e to attem pt early repair. blu nt techniqu e and throu gh ju d iciou s u se of electro-
The constru ction of an effective Rou x-en-Y hep aticoje- cau tery bu t can be facilitated in d ifficu lt cases by the u se
ju nostom y is critical to the long-term resu lts of all p atients of an u ltrasonic or hyd rojet d issector. Bleed ing m ay be
FIGURE 35.5. Hepp–Couinaud

method to expose the left portal
plate and the extrahepatic portion
of the left hepatic duct.
Ligamentun teres
encou ntered d u ring this techniqu e, but can be stop p ed by nificant intrahep atic d issection. Mercad o et al. (59,76) have
packing gau ze or other hem ostatic m aterial into the hep a- d escribed a lim ited resection of liver segm ent 5 and som e-
totom y for a p eriod of tim e. Returning to this area after tim es 4B to facilitate exp osu re of the right hepatic d u ct
com p leting other tasks, su ch as creating the enteroenteros- w ithin the p arenchym a. These anastom oses m ay be facili-
tom y of the Rou x lim b, allow s perform ance of the biliary tated by the presence of bilateral transhepatic biliary stents.
anastom osis in a d ry and controlled field . In the case of inju ries m anaged in a d elayed fashion, a U
Thou gh p erhaps cou nterintu itive to su rgeons not exp e- tu be (transhepatic biliary stent entering the right d u ctal
rienced w ith these com plex repairs, creation of a long d u c- system , crossing the bifu rcation, and exiting the left d uctal
totom y that crosses the hep atic d u ct bifu rcation and system ) offers an effective and stable m ethod of extrahep-
incorporates exposure of all m ajor hepatic d ucts is essential atic d rainage (Fig. 35.7). The U tu be can then be exchanged
to a d u rable rep air. Mistakes can be m ad e in Typ e E2 or E3 for sep arate bilateral silastic catheters at the tim e of rep air,
injury repairs by exp osing only the scarred conflu ence of w ith an ind ivid u al tu be across each of the right and left
the hep atic d u ct at or below the bifurcation, reasoning that d u ctal anastom oses.
a “single-barrel” anastom osis w ould be technically sim p ler All biliary anastom oses of these com p lex inju ries
to p erform . This approach ignores the im portance of id enti- sh ou ld be performed und er loupe magnification, using fine
fying healthy d u ctal tissu e w ith preserved blood su p p ly, by monofilament absorbable suture, typically in an interrupted
d issecting carefu lly above the level of injury. Winslow et al. fashion. Placement of subhepatic drains to monitor for bil-
(60) d escribed this ap p roach nicely as the “sid ew ays” iary leak is typically performed . After completion of the bil-
techniqu e, allow ing a long “sid e-to-sid e” hep aticojeju nos- iary anastomosis, the Roux limb can be further anchored to
tom y that cou ld be ad ap ted to variations in the sectoral relieve tension by taking seromuscular bites of the jejunum
biliary d rainage (Fig. 35.6). Use of the left hep atic d u ct to and tacking it to the former gallblad d er fossa, portal plate, or
extend the length of the hep aticojeju nostom y is a key ele- umbilical fissure.
m ent, as d escribed by Cou inau d (73), H epp (74), and Voyles
and Blu m gart (75).
The m anagem ent of Type E4 and E5 inju ries can be even
■ Associated vascular injury
more challenging. Sep arate anastom oses to right and left Associated vascu lar inju ry is n ot u ncom m on in bile d u ct
d u cts are often requ ired , althou gh som etim es a central p or- inju ry an d m ay be associated w ith both acu te liver inju ry
tion of the form er hep atic d u ct bifu rcation can be u sed to and d elayed biliary strictu re d u e to ischem ia. Significant
brid ge a long “d ou ble-barreled ”-type anastom osis. Exp o- vascu lar inju ry associated w ith a m easu rable rise in liver
sure to the left hepatic d u ct is often straightforw ard , as en zym es an d system ic inflam m atory resp on se is a rela-
d escribed earlier, bu t reaching a healthy portion of the tive con traind ication to early rep air of bile d u ct inju ry, as
right hep atic d uct or its proxim al branches can requ ire sig- n ot only m ay th e p atien t not be op tim ized for w hat m ay
FIGURE 35.6. Longitudinal ductotomies performed to facili-

tate side-to-side hepaticojejunostomy for Type E1, Type E2, and
Type E3 biliary injuries. (Reproduced with permission from
Winslow ER, Fialkowski EA, Linehan DC, et al. “Sideways”:
results of repair of biliary injuries using a policy of side-to-side
hepaticojejunostomy. Ann Surg 2009;249(3):426–434) (60).
be a com p lex op eration, bu t w ill also not allow for collat- p ostop erative rad iologic stu d ies. Strictu res secon d ary to
eral blood flow to involved biliary segm ents to m atu re arterial in su fficien cy m ay d evelop over a longer p eriod of
over tim e p rior to d efinitive rep air. Fortu nately, segm en- tim e than technical failu res resu lting from a su bop tim al
tal hep atic vascu lar inju ries d o not typ ically requ ire an astom osis or other m ech anism s of in ju ry, su ch as a
reconstru ction d u e to the red u nd ant blood flow to the therm al inju ry (79).
liver (77). Excep tions to this general ru le w ou ld inclu d e
ligation or severe stenotic inju ry to the m ain p ortal vein ■ Long-term outcomes following repair
or p rop er hep atic artery. Unrecognized vascu lar inju ry,
of bile duct injury
p articu larly to th e righ t h ep atic artery, m ay be m ore com -
m on than ap p reciated an d ap p ears to be associated w ith In exp erienced hand s, rep air of bile d u ct inju ry shou ld be
a high rate of biliary strictu re follow ing rep air (78,79). associated w ith excellent short-term resu lts and restoration
Vascu lar inju ries ap p ear to be associated w ith high bile of p atients to a good qu ality of life (23,54,60,80,81).
d u ct inju ries of Typ es E3 to E5 and sh ou ld be su sp ected H ow ever, the rate of d elayed stricture formation is prob-
in cholecystectom ies w ere excessive bleed ing w as ably as high as 15% to 20% (54,81). Risk factors for d elayed
rep orted or m u ltip le ( 6) su rgical clip s are visu alized on strictu re form ation includ e associated vascu lar inju ries,
A B
C D
FIGURE 35.7. Type E3 biliary injury managed with U tube percutaneous biliary drainage and delayed Roux-en-Yhepaticojejunostomy.
Percutaneous transhepatic cholangiography on POD 5 following laparoscopic cholecystectomy reveals Type E3 injury with biliary leak
(Panel A). A wire was able to be passed from percutaneous access to the right hepatic duct, across the hepatic duct bifurcation and
retrieved from percutaneous access to the left hepatic duct, allowing placement of a U tube for external biliary drainage (Panel B). The
patient recovered over the ensuing 12 weeks, during which time the biliary leak resolved with stable U tube drainage (Panel C). At the
time of hepaticojejunostomy, the U tube was exchanged for individual bilateral biliary catheters placed across the anastomosis. The
catheters were removed 3 weeks after repair when cholangiogram revealed a well-healed patent hepaticojejunostomy (Panel D).
Type E3 to E5 injuries, and the need for revision of an initial eliminate later surgical op tions. In refractory cases of biliary
attemp t at primary repair. Strictu res ap pear to present most stricture, associated second ary biliary cirrhosis and liver
commonly in the first 2 years after d efinitive repair, bu t can d ysfunction may occur. While liver transplantation has
present in a more d elayed fashion, emphasizing the need been reported for severe and u nreconstructable bile d uct
for longitu d inal follow -up of these patients (55,82). When inju ries, this shou ld be an op tion rarely em ployed given
biliary strictu res d o occur, the vast majority can be managed mod ern surgical and interventional techniques to establish
w ithout operative intervention, relying on percutaneous ad equ ate biliary d rainage (23).
stenting and cholangioplasty (54,60). In patients refractory
to conventional balloon cholangioplasty, internal metallic
stents have been proposed as effective interventions w ith a
■ RETAINED COMMON BILE DUCT STONES
AFTER CHOLECYSTECTOMY
high rate of su ccess in strictured hepaticojejunostom ies (83).
Covered m etallic stents offer a seem ingly attractive op tion It is estim ated that 10% to 18% of p atients p resenting for
as they d o not foster ingrow th and can be removed after cholecystectom y w ith an ind ication of cholelithiasis w ill
temporary placement (84). H ow ever, these interventions have com m on bile d u ct stones (85–89). When suspected
are likely best reserved for patients that cannot und ergo p reop eratively, end oscop ic and su rgical ap proaches to
operative revision, as placement of metallic stents may m anagem ent of choled ocholithiasis are available, w ith
recent resu lts su ggesting that the strategies m ay be equ iva-

lent in efficacy and should be selected based up on local
expertise and ind ivid u al patient consid erations (90). The
use of IOC, as d iscu ssed earlier, m ay be guid ed by the su s-
picion of choled ocholithiasis at the time of cholecystec-
tom y. In 1% of p atients, choled ocholithiasis w ill p resent
follow ing cholecystectom y (56). This d elay in presentation
is d ue to a lack of app ropriate su spicion of the d iagnosis
preoperatively, d u e to failu re to d em onstrate com m on d u ct
stones at cholangiograp hy p erform ed either intraop era-
tively or end oscop ically, or d ue to stone m igration that
occu rs at the tim e of cholecystectom y.
Clinical p resentation w ith retained com m on bile d u ct
stones follow ing cholecystectom y typ ically occu rs in the
first 2 w eeks p ostop eratively. Sym p tom s m ay inclu d e
abd om inal p ain, jau nd ice, fever, nau sea, and em esis. Labo-
ratory evalu ation w ill reveal an abnorm al liver p rofile,
p articu larly w ith elevation of the total biliru bin and alka-
line p hosp hatase. Concom itant elevation of am ylase and
lip ase shou ld raise high su sp icion of this d iagnosis, su g- FIGURE 35.8. Magnetic resonance cholangiopancreatography demon-
gesting a d istal biliary or am p u llary obstru ction, as strating common bile duct stones. Arrow points to two stones in the distal com-
mon bile duct.
op p osed to m ore p roxim al biliary obstru ction follow ing
cholecystectom y that w ou ld not typ ically cau se p ancreati-
tis and shou ld raise concern abou t bile d u ct inju ry.
Becau se bile d u ct inju ry is the other m ajor d iagnosis in the ap p rop riate in clinical scenarios w here choled ocholithiasis
d ifferential of retained bile d u ct stones, the d iagnostic is suspected but not confirm ed by conventional im aging
evalu ation shou ld p roceed in a sim ilar m anner. Right stu d ies. In ad d ition, EUS may be ap p rop riate in patients
u p p er qu ad rant u ltrasou nd is a reasonable initial d iagnos- w ho have an abnorm al bu t im p roving liver p rofile, as a
tic test and can som etim es visu alize d istal bile d u ct stones. method to confirm that any com m on d uct stones have
H IDA scan can be a u sefu l ad ju nct in cases w here obstru c- p assed sp ontaneou sly. This allow s su ch “interm ed iate-
tion or biliary d ilatation is not clear, as this test can d ocu - risk” p atients to avoid biliary cannu lation and sp hinctero-
m ent any associated biliary leak or obstru ction. H ow ever, tom y u nless the EUS confirm s choled ocholithiasis, an
as w ith the d iagnosis of bile d u ct inju ry, cholangiograp hy algorithm that ap p ears to be accu rate and safe (99). A
is the d efinitive test to d iagnose retained com m on bile recent m eta-analysis su ggests that p erform ing EUS first
d u ct stones. cou ld allow avoid ance of ERCP in u p to 67% of patients
w ith su sp ected choled ocholithiasis (100). A sim ilar p rinci-
p le of “EUS-first” has been d em onstrated in other stud ies,
■ Endoscopic therapy of common bile duct stones includ ing the investigation of patients w ith su spected bil-
In the p ostop erative setting, ERCP is the p referred iary p ancreatitis (101,102). An obviou s ad vantage of EUS
m eth od for m an agin g ch oled ocholithiasis (91). Thou gh over other noninvasive stu d ies, nam ely MRCP, is that
p ast stu d ies d ebated the role for ERCP an d su rgical ERCP can im m ed iately be u sed in the sam e end oscop ic
m eth od s of com m on bile d u ct ston e extraction (92,93), p roced u re if EUS find ings confirm choled ocholithiasis. Of
m ore recen t d ata su ggest th at ERCP is a safe and effective cou rse, EUS requ ires a skilled end oscop ist that m ay not be
ap p roach, p articu larly in th e p ostop erative settin g (94). available in all centers. Thu s, MRCP m ight be equ ally
Com p lications of ERCP in clu d e p ancreatitis, d u od en al ap p rop riate to aid in the d iagnosis of p atients w ith su s-
p erforation , and bleed in g, thou gh life-threatenin g com - p ected bu t not confirm ed choled ocholithiasis (Fig. 35.8), as
p lication s sh ou ld occu r in 1% of cases (95,96). Risk fac- a w ay of avoid ing u nnecessary ERCP (103).
tors for com p lications follow ing ERCP inclu d e com orbid Acute cholangitis d u e to choled ocholithiasis is a rela-
d isease, obesity, or len gthy or com p licated p roced u res tively rare bu t seriou s p roblem , occu rring in 6% to 9% of
(95). Recen t p rosp ective stu d ies d ocu m ent that ERCP is p atients w ith sym p tom atic gallstone d isease (92). Prior to
effective in clearing the bile d u ct of retained stones in the ad vent of end oscop ic ap p roaches, op en com m on bile
93% to 96% of cases (92,97–99). d u ct exp loration w as the stand ard of care for this problem ,
Given the rare bu t notable incid ence of p ost-ERCP com - w ith a m ortality rate of 10% to 40% (92). The u se of ERCP in
plications, efforts have been m ad e to avoid biliary cannu la- this setting has significantly d ecreased the m ortality rate to
tion and sp hincterotom y u nless absolu tely necessary. The the range of 0.4% to 7%. For p atients w ho are acutely ill
use of EUS has p rovid ed an ad d itional d iagnostic m od ality w ith cholangitis d u e to com m on bile d u ct stones, the over-
to d iagnose choled ocholithiasis and ap p ears to be m ost all su ccess rate for ERCP cannu lation is 95%. In this setting,
84% of p atients have been noted to have stones, and biliary

d ecom p ression w as achieved in all patients (92). Transhep -
atic p ercu taneou s rou tes to biliary d ecom p ression can be
consid ered in patients w ho fail end oscopic biliary d ecom -
pression for cholangitis, w ith little role for su rgical
ap p roaches in the acu te setting.
■ Surgical management of common

bile duct stones
Su rgical com m on bile d u ct p roced u res for stone d isease are
becom ing increasingly less com m on w ith the ad vancing
efficacy and versatility of end oscopic therapies. H ow ever,
these techniqu es w ill alw ays have a p lace in select circu m -
stances w here either end oscop ic or p ercu taneou s p roce-
d u res fail to relieve biliary obstruction, or w hen ERCP is
not feasible d u e to anatom ic constraints (e.g., gastric
byp ass). In ad d ition, choled ocholithiasis recognized p reop -
eratively can be safely m anaged in experienced hand s
either by sequ ential ERCP and cholecystectom y, or w ith
concomitant cholecystectom y and com mon bile d uct
exploration (91,92). When perform ed laparoscop ically by
experienced op erators, com m on bile d u ct exp loration
ap p ears effective in 80% of cases in extracting com m on
bile d u ct stones, w ith ERCP reserved for cases w here stone
extraction w as u nsuccessful or choled ocholithiasis w as not
recognized u ntil the p ostoperative period (91,104).
Com m on bile d u ct exp loration can be perform ed using
either a transcystic techniqu e or choled ochotom y. If stones
are 15 m m, a transcystic approach m ay be em p loyed
(104). Stones 15 m m are an ind ication for choled o-
chotom y, and stones 25 m m m ay requ ire conversion to an
open p roced u re. If the initial transcystic approach d oes not
allow satisfactory rem oval of large stones or fragm ents, a FIGURE 35.9. Endoscopic retrograde cholangiopancreatography of a stric-
choled ochotom y is ind icated . Choled ochoscop y allow s tured choledochoduodenostomy with a stone above the stricture. Arrow
d irect visu alization of the d uct system. A com p letion points to stone.
cholangiogram should alw ays be perform ed after all stone
extraction is com plete. If there are concerns abou t the p os-
sibility of retained stones, a T-tube may be inserted either via ap p roaches (105–107). Rou x-en-Y choled ochojeju nostom y
the cystic d uct stump or via the choled ochotomy, although is typ ically m ore involved to p erform and p reclu d es later
postoperative ERCP is also a reasonable approach. Observa- end oscop ic evalu ation and treatm ent. Both short-term
tion in equivocal cases could be consid ered as most small and long-term risks of cholangitis are sim ilar for choled o-
stones pass spontaneously, though no prospective d ata sup- chod u od enostom y and choled ochojeju nostom y. The m or-
port a policy of expectant management of retained common tality rates for both p roced u res are sim ilar, ap p roxim ating
bile duct stones. 1.5% to 6% (107). Choled ochod u od enostom y has a long-
Patients w ith refractory stone d isease or associated d is- term risk of cholangitis that ranges from 0% to 12%; this
tal bile d u ct inflam m atory strictu res can be d efinitively com p lication is u su ally associated w ith strictu re form a-
treated w ith either choled ochod uod enostomy or Roux-en-Y tion at the anastom osis (Fig. 35.9) (107). Strictu re m ay be
choled ochojeju nostom y. Both p roced u res have been m inim ized by p erform ing a m u cosa-to-m u cosa anasto-
ad vocated for p atients w ith a high p robability of stone m osis of at least 14 m m length. Follow ing Rou x-en-Y
retention and recu rrent stone form ation. Ind ications choled ochojeju nostom y, a similar rate of cholangitis is
inclu d e d ifficu lty in extracting stones; the p resence of soft seen, m ost com m only d u e to resid u al intrahepatic stones
friable stones; retained , recu rrent, or im p acted stones; a (107). Choled ochojeju nostom y is recom mend ed w hen
d ilated com m on bile d u ct w ith or w ithou t associated there has been a p rior bile d u ct rep air, w hen there is a d iffi-
am p u llary stenosis; m u ltip le intrahep atic stones; or m u l- cu lt or recu rrent biliary strictu re, or w hen the d u od enu m is
tip le com m on d u ct stones. Choled ochod u od enostom y is scarred , obstru cted , or cannot be safely m obilized for an
easier to p erform and is am enable to m inim ally invasive anastomosis.
■ UNRECOGNIZED GALLBLADDER CANCER Table 3 5 .2 AJCC st a gin g for ga llbla d d er ca n cer,

6t h ed . (115)
Postop erative d iagnosis of gallblad d er cancer follow ing
cholecystectom y (i.e., on p athology of the gallblad d er T Classification
sp ecim en) is a rare bu t vexing clinical p roblem . Gallblad - Tis Carcinoma in situ
d er cancer is an u ncom m on d isease, w ith 10,000 cases T1a Tumor invades mucosa to lamina propria only
annu ally in the United States (108). Long-term su rvival is T1b Tumor invades muscle layer
p oor (5-year su rvival 5% to 10%), w ith nonincid ental T2 Tumor invades perimuscular connective tissue; not beyond
cases of the d isease p resenting nearly u niversally at serosa
ad vanced stages w ith fatal ou tcom es (108). Recent d ata T3 Tumor perforates serosa and/or invades liver to any depth
and/or one other adjacent organ or structure
su ggest that an increasing p rop ortion of gallblad d er can-
T4 Tumor invades main portal vein or hepatic artery or invades
cer p atients are being d iagnosed incid entally (109).
multiple extrahepatic organs or structures
Althou gh several rep orts initially su ggested an increased
rate of p ort site or p eritoneal seed ing after lap aroscop ic N Classification
N1 Regional lymph node metastases (cystic, pericholedochal,
cholecystectom y in the setting of gallblad d er cancer
and/or hilar nodes)
(110,111), a m u lticenter evalu ation d em onstrated that the
p rognosis of u nsu sp ected gallblad d er cancer w as no M Classification
w orse after lap aroscop ic than after op en cholecystectom y M1 Metastasis to distant organs and/or to peripancreatic, periduo-
denal, celiac, superior mesenteric nodes
(112–114). Su rvival correlates w ith stage of d isease and
w ith bile sp illage d u ring the first op eration. Release of Stage
tu m or cells inevitably occu rs d u ring cholecystectom y if Stage 0 Tis N0 M0
the tu m or is located on the hep atic su rface d u ring resec- Stage IA T1 N0 M0
Stage IB T2 N0 M0
tion of the gallblad d er from the liver bed . This factor m ay
Stage IIA T3 N0 M0
exp lain p eritoneal tu m or seed ing that is som etim es seen
Stage IIB T1–3 N1 M0
in the absence of bile sp illage. Stage III T4 NXM0
Du ring lap aroscop ic cholecystectom y, the gallblad d er Stage IV TXNXM1
shou ld be op ened im m ed iately after extraction to d etect a
p ossible m alignancy. If a m alignancy is su sp ected , a
frozen section shou ld be obtained . If gallblad d er cancer is
p athologically confirm ed , the abd om en shou ld be irri- p rognosis. In p atients w ith T2 d isease, rad ical resection
gated w ith a large volu m e of saline in an attem p t to p reap p ears to significan tly im p rove su rvival (61% 5-year
vent im p lantation of m alignant cells. Ad d itional su rgery su rvival w ith rad ical resection vs. 19% w ith sim p le chole-
is not recom m end ed u ntil the final p athology rep ort to cystectom y) (116) and is associated w ith a high yield of
obtain accu rate staging, as it is often d ifficu lt to d eterm ine ad d itional resid u al d isease (57% of p atients) (117). In
d ep th of invasion based on frozen section. Delay of d efin- p atients w ith T3 d isease, 80% of p atients w ill have resid -
itive su rgical therap y d oes not have an ad verse effect on u al d isease in either the p ortal nod es or liver p arenchym a
p rognosis (114). (117), and 5-year su rvival is notably w orse at 25% (116).
The m anagem ent of p atients w ith T1 incid ental gall-
blad d er cancer is m ore challenging. Patients w ith T1a
■ Surgical treatment of incidental d isease, that is, d isease that invad es the m u cosa only to the
gallbladder cancer
Decision -m akin g abou t the role of ad d itional su rgery for
p atients w ith incid entally d iagnosed gallblad d er cancer is
Table 3 5 .3 Recom m en d ed su r gica l t r ea t m en t
prim arily based u p on the pathologic T stage of the tu m or,
for ga llbla d d er ca n cer
as d etailed in the sixth ed ition of the AJCC staging gu id e-
lines and ou tlined in Table 35.2 (115). Recom m end ations Pathologic T Stage Recommended Surgical Therapy
for appropriate surgical therapy are detailed in Table 35.3. Tis Simple cholecystectomy
Patients with T2 and T3 tumors who are good surgical can-
T1a Simple cholecystectomy
did ates shou ld u nd ergo resection of segm ents 5 and 4B of
the liver, w ith associated p ortal lym p had enectom y. For T1b Segment 4B/5 hepatic resection portal
patients who have und ergone laparoscopic cholecystectomy lymphadenectomy
prior to radical resection, port site excision is also recom- T2 Segment 4B/5 hepatic resection portal
mend ed . Resection of the extrahepatic biliary tree is also lymphadenectomy
som etimes ind icated if there is d irect involvement of this T3 Segment 4B/5 hepatic resection portal
area, or if the cystic duct stump margin is positive. More rad- lymphadenectomy
ical resections may be undertaken in order to achieve micro- T4 Surgical therapy not indicated
scopically negative margins, w hich significantly im p rove
layer of the lam ina prop ria, have excellent outcom es w ith technique. H and ling of the biliary d u ct prior to the anasto-
sim p le cholecystectom y alone. In patients w ith T1b d isease m osis is im p ortant, w ith attention p aid to avoid ing exces-
invad ing the m u scu lar layer of the gallblad d er, the inci- sive d issection that strip s the p erid u ctal blood supp ly. The
d ence of associated nod al d isease upon portal lym - bile d u ct shou ld be cu t sharp ly, w ith bleed ing controlled by
phad enectom y is 12% to 15% (117,118). Desp ite this p ressu re or fine absorbable su tu re, rather than using ther-
reasonable likelihood of resid ual d isease, the su rvival for m al energy that m ay d am age the m ost d istal extent of the
T1b gallblad d er cancer w ith sim ple cholecystectomy is 85% d u ct. Exp osu re is critical to being able to visualize every
to 96% (119,120). As the m orbid ity of rad ical resection for stitch, and techniqu es u sed to p resent the d u ct su ch that
gallblad d er cancer should be low in experienced hand s each su tu re m ay be p laced accu rately shou ld be em ployed
(117), cu rrent recom m end ations su pport resection for T1b (21,124).
disease, though acknow ledging this approach may overtreat
a m ajority of p atients in hop es of imp roving the su rvival of ■ Early complications following biliary–
a few (121).
enteric anastomosis
■ COMPLICATIONS OF BILIARY–ENTERIC Early postop erative com plications of these proced u res
inclu d e external biliary fistu la and bile p eritonitis, usually
ANASTOMOSIS
related to an anastom otic leak. If this com p lication occurs,
Other standard biliary operations for which complications p ercu taneou s d rainage of bile collections is the preferred
can be considered are those procedures that include a bil- ap p roach, avoid ing reop eration. If reop eration is requ ired ,
iary–enteric anastomosis. Biliary–enteric anastomoses can be it shou ld not typically be com bined w ith any im med iate
included in resection or bypass procedures, or as part of the attem p ts at biliary rep air, as the biliary tissu e qu ality is
liver transplant operation. They can vary in complexity from often qu ite friable and p rone to fu rther com p lications w ith
the relatively straightforward, such as a choledochoduo- another attem p t at anastom osis. Broad sp ectrum antibiotic
d enostomy on a large chronically obstructed d istal common therap y shou ld be u tilized and catered to cu ltu res of
bile d u ct, to the highly technical, such as segmental or mul- d rained p eritoneal collections. Control of sep sis is the first
tiple d uct anastomoses as a hepaticojejunostomy follow ing and m ost u rgent p riority.
a complicated hepatobiliary resection. Biliary–enteric anas- Many biliary anastom otic leaks w ill requ ire establish-
tomoses can be includ ed as part of the operation for both ing control of biliary d rainage to achieve resolution. ERCP
benign and malignant d isease of the hepatobiliary tract. w ith end obiliary stenting and PTC w ith p lacement of a
Despite these protean applications, the important complica- p ercu taneou s transhep atic biliary d rain are the options for
tions follow ing these biliary p roced u res generally p resent gaining control and d iverting biliary flow aw ay from a bil-
as either leak or strictu re, and their managem ent p rincip les iary leak. Decisions betw een these tw o p roced ures shou ld
are sim ilar regard less of the p atient and ind ication for the be m ad e based u p on anatom ic consid erations, as ERCP is
proced u re. Control of infection and m aintenance of ad e- likely only applicable to choled ochod u od enostom ies or
qu ate biliary d rainage are param ou nt to their effective m ore p roxim al jeju nal anastom oses that can be reached by
managem ent. d ou ble-balloon techniqu es (125). In som e cases of seg-
The incid ence of com p lications follow ing biliary– m ental biliary anastom oses—su ch as those p erformed
enteric anastom osis is variable and d epend ent in large part follow ing an extend ed hepatic resection w ith biliary recon-
on the ind ication and clinical setting. Biliary leak and stric- stru ction, or living d onor liver transp lantation—surgeons
tu re m ay be seen in u p to 20% of patients follow ing liver may elect not to percutaneou sly access the biliary tree for
transp lantation (122), likely d ue to the ad d ed im p act of control of a sm all or w ell-controlled biliary leak. In these
associated ischem ia–reperfu sion inju ry of the allograft, bu t cases, the d ifficu lty of the PTC m ay be greater than the
shou ld be relatively u ncom m on in other circu m stances morbid ity of a m od est biliary leak, and generally, these
even after a com plex hep aticojeju nostom y (54,60). In m ore leaks w ill resolve over tim e as long as the anastom osis is
routine biliary anastom oses, leak or strictu re shou ld be rare not com p letely d isru p ted . Biliary–enteric stents, w hether
occu rrences in 3% to 5% of patients (107,123). p laced end oscop ically or p ercu taneou sly, shou ld be left in
As w ith bile d u ct injury after cholecystectom y, u nd er- p lace u ntil any associated sep sis is resolved , the leak has
stand ing com p lications follow ing the biliary–enteric anas- been d em onstrated to be sealed by rep eat cholangiography,
tom osis is d erived from com p rehension of their etiology and the p atency of the biliary–enteric anastom osis is estab-
and p revention. The p rinciples inherent to a su ccessfu l bil- lished . Rep lacem ent of stents left for 4 to 6 w eeks is nec-
iary–enteric anastom osis inclu d e exposu re of a healthy and essary to prevent stent occlu sion and su bsequent biliary
w ell-vascu larized bile d u ct, a w ell-apposed ep ithelial to obstru ction or cholangitis.
m u cosa anastom osis free of tension , u se of absorbable Biliary leak, p articu larly follow ing hep atic resection or
su tu re, and a healthy and u nobstru cted p ortion of the liver transp lantation, is a risk factor for the d evelopm ent of
enteric tract as th e d istal target. Early com p lication s after hem obilia, a rare bu t highly m orbid com p lication (126).
a biliary–enteric an astom osis are m ost often tech nical in The etiology of this com p lication ap p ears to arise from the
natu re and can be avoid ed by m eticu lou s atten tion to trau m atic natu re of biliary d rainage on ad jacent vessels,
particu larly if the vessels them selves have been inju red or
surgically ligated . Branches of the hepatic artery are typ i-
cally involved , thou gh portal fistu las can also occur. These
injuries can probably at tim es d evelop second ary to proce-
d u res to ad d ress an associated biliary leak, as both ERCP
and PTC-p laced stents have been associated w ith ad jacent
artery erosion or p seu d oaneurysm form ation (127–129).
Arterial pseu d oaneurysm s typ ically present w ith a herald
bleed that m ay be follow ed by m ore catastrophic hem or-
rhage. When hem obilia is su spected , visceral angiograp hy
should be p erform ed em ergently. Em bolization of id enti-
fied p seu d oaneu rysm s can be d efinitive, thou gh hep atic
artery reconstru ction m ay be necessary in som e circu m -
stances w hen p ercu taneou s em bolization either is not feasi-
ble or w ou ld be associated w ith occlu sion of hep atic inflow.
■ Late complications of biliary–enteric

anastomoses
Anastomotic stricture is the most commonly delayed com-
plication of the biliary–enteric anastomosis, and it may pres-
ent w ith jaundice or cholestasis, cholangitis, obstruction, FIGURE 35.11 Percutaneous transhepatic cholangiography of the stric-
tured biliary–enteric anastomosis illustrated in Figure 35.10 following suc-
and/ or stone formation. When suspected, cholangiography cessful balloon dilatation. Arrow indicates the area of prior stricture.
should be performed . MRCP offers a noninvasive means of
documenting anastomotic stricture, and associated contrast-
enhanced MRI can assess for associated vascular injury or
other anatomic concerns that may be associated w ith biliary endoscopic attempts at cholangioplasty and stenting. Multi-
stricture formation. Once d ocum ented , d irect cholangiogra- ple studies document the efficacy of percutaneous tech-
phy by either ERCP or PTC—as anatomically appropriate— niques in managing biliary–enteric strictures in 75% of
can be d efinitive and therapeutic (Fig. 35.10). Operative patients (128,130–132). While some patients required two to
revision of a biliary–enteric anastomosis should be reserved four proced ures, the long-term ability to avoid surgical revi-
for appropriate surgical cand id ates that fail percutaneous or sion is notable (Fig. 35.11).
Althou gh self-expand ing m etallic stents are quite u sefu l
in the treatm ent of inoperable m alignant biliary strictures
(133,134), their u se in the treatm ent of benign strictu res is
controversial. Stu d ies have examined the resu lts of the u se
of self-exp and ing m etallic stents for the treatm ent of
benign biliary strictu res w ith reasonable follow -u p period s
(83,135). The au thors conclu d ed that su rgical rep air
shou ld rem ain the m ainstay of treatm ent for benign biliary
strictu res, w ith m etallic stents reserved for p atients w ho
are p oor su rgical cand id ates, have intrahep atic biliary stric-
tu res or after m u ltip le u nsu ccessfu l attem p ts at op erative
rep air. Most of these p atients eventu ally d evelop recurrent
cholangitis and stent obstru ction and requ ired rep eat
intervention. Du ctal m u cosal hyp erp lasia d evelop s in res
p onse to stents and is a contribu ting factor to stent obstruc-
tion. The incorp oration of the stent into the biliary w all can
cau se severe inflam m ation, w hich can com p licate stent
rem oval if this becom es necessary. The m ean stent patency
interval in p u blished series w as 30.6 m onths (83,135). In
ad d ition, there are concerns that chronic inflam m ation and
obstru ction m ay p red isp ose to the d evelop ment of cholan-
giocarcinom a. Althou gh the risk of cholangiocarcinom a is
w ell d ocu m ented in association w ith p rim ary sclerosing
FIGURE 35.10. Percutaneous transhepatic cholangiography of a strictured
hepaticojejunostomy, originally performed to treat a Type E2 bile duct injury. cholangitis, it has not been p reviou sly d ocu m ented in the
Arrow illustrates the strictured biliary–enteric anastomosis. context of other benign strictu res. The recent introd uction
of covered m etallic biliary stents m ay exp and their ap p lica- 14. Archer SB, Brow n DW, Sm ith CD, et al. Bile d u ct inju ry d u ring lap aro-
scop ic cholecystectom y: resu lts of a national su rvey. Ann Surg
tion, as these stents m ay stim ulate less associated tissu e 2001;234(4):549–558; d iscu ssion 558–559.
ingrow th and inflam m ation and m ay be rem oved in a 15. Strasberg SM. Biliary inju ry in lap aroscop ic su rgery: p art 2. Changing
d elayed fashion (84). More recently, d egrad able biliary the cu ltu re of cholecystectom y. J Am Coll Surg 2005;201(4):604–611.
16. Strasberg SM. Biliary inju ry in lap aroscop ic su rgery: p art 1. Processes
stents have been p rop osed and m ay be ap p lied m ore com - used in d eterm ination of stand ard of care in m isid entification injuries.
monly in fu tu re applications (136). J Am Coll Surg 2005;201(4):598–603.
17. Way LW, Stew art L, Gantert W, et al. Cau ses and p revention of lap aro-
scop ic bile d u ct inju ries: analysis of 252 cases from a hu m an factors
■ CONCLUSIONS and cognitive p sychology p ersp ective. Ann Surg 2003;237(4):460–469.
18. Strasberg SM, Eagon CJ, Drebin JA. The “hid d en cystic d u ct” syn-
Biliary proced ures are com m on operations in general sur- d rom e and the infu nd ibu lar techniqu e of lap aroscop ic cholecystec-
gery, and comp lications m ay generate consid erable p atient tom y—the d anger of the false infu nd ibu lu m . J Am Coll Surg 2000;
191(6):661–667.
morbid ity and risk of m ortality. Com plications after chole- 19. David off AM, Pap p as TN , Mu rray EA, et al. Mechanism s of m ajor bil-
cystectom y inclu d e bile d u ct inju ry, the m anagem ent of iary inju ry d u ring lap aroscop ic cholecystectom y. Ann Surg 1992;
w hich is p red icated u p on early recognition and exp ert 215(3):196–202.
20. Branu m G, Schm itt C, Baillie J, et al. Managem ent of m ajor biliary
managem ent. Retained com m on bile d uct stones can be complications after laparoscopic cholecystectomy. Ann Surg 1993;217(5):
d ealt w ith throu gh end oscopic, percu taneous, or su rgical 532–540; d iscu ssion 540–541.
techniqu es w ith good results. Incid ental gallblad d er cancer 21. Cam eron JL, Sand one C. Atlas of gastrointestinal surgery, 2nd ed .
H am ilton: BC Decker; 2007.
d iagnosed after cholecystectom y shou ld be m anaged 22. Souba WW, Fink MP, Jurkovich GJ, et al.; for Am erican College of Su r-
based u p on p athologic T staging, w ith T1b, T2, and T3 can- geons. ACS surgery: principles & practice 2004. N ew York, N Y: WebMD
cer outcom es im proved by su bsequ ent hep atic resection Professional Pu b; 2004, xxiii, 1505.
23. Chap m an WC, Abecassis M, Jarnagin W, et al. Bile d u ct inju ries 12
and p ortal lym p had enop athy. years after the introd uction of lap aroscop ic cholecystectom y. J Gas-
Com p lications follow ing biliary–enteric anastom osis trointest Surg 2003;7(3):412–416.
inclu d e leak and strictu re. Both these comp lications requ ire 24. Strasberg SM, Brunt LM. Rationale and u se of the critical view of
safety in laparoscopic cholecystectom y. J Am Coll Surg 2010;211(1):
accu rate and p rom p t d iagnosis to lim it p atient m orbid ity, 132–138.
bu t can typ ically be managed w ithout the need for reop er- 25. Yegiyants S, Collins JC. Op erative strategy can red u ce the incid ence of
ation. The effective m anagem ent of all biliary com p lica- m ajor bile d u ct inju ry in lap aroscop ic cholecystectom y. Am Surg
2008;74(10):985–987.
tions is d ep end ent on control of associated intraabd om inal 26. Avgerinos C, Kelgiorgi D, Tou lou m is Z, et al. One thou sand lap aro-
sep sis and establishm ent of d efinitive biliary d rainage. scop ic cholecystectom ies in a single su rgical u nit u sing the “critical
view of safety” techniqu e. J Gastrointest Surg 2009;13(3):498–503.
27. H eisterm ann H P, Tobu sch A, Palm es D. Prevention of bile d u ct
■ REFERENCES inju ries after laparoscop ic cholecystectom y. “The critical view of
safety” [in Germ an]. Zentralbl Chir 2006;131(6):460–465.
1. Shaffer EA. Gallstone d isease: ep id em iology of gallblad d er stone d is- 28. Wau ben LS, Goossens RH , van Eijk DJ, et al. Evalu ation of p rotocol
ease. Best Pract Res Clin Gastroenterol 2006;20(6):981–996. u niform ity concerning lap aroscop ic cholecystectom y in the N ether-
2. Russo MW, Wei JT, Thiny MT, et al. Digestive and liver d iseases statis- land s. World J Surg 2008;32(4):613–620.
tics, 2004 Gastroenterology 2004;126(5):1448–1453. 29. Plaisier PW, Pau w els MM, Lange JF. Qu ality control in lap aroscop ic
3. McMahon AJ, Russell IT, Baxter JN , et al. Lap aroscop ic versu s m inila- cholecystectom y: op eration notes, vid eo or p hoto p rint? HPB (Oxford)
parotom y cholecystectom y: a rand om ised trial. Lancet 1994;343(8890): 2001;3(3):197–199.
135–138. 30. Flu m DR, Dellinger EP, Chead le A, et al. Intraop erative cholangiogra-
4. Jackson H , Granger S, Price R, et al. Diagnosis and lap aroscop ic treat- p hy and risk of com m on bile d u ct inju ry d u ring cholecystectom y.
m ent of surgical diseases during pregnancy: an evidence-based review . JAMA 2003;289(13):1639–1644.
Surg Endosc 2008;22(9):1917–1927. 31. Richard son MC, Bell G, Fu llarton GM; for West of Scotland Lap aro-
5. Brunt LM, Qu asebarth MA, Du nnegan DL, et al. Ou tcom es analysis of scop ic Cholecystectom y Au d it Grou p . Incid ence and natu re of bile
laparoscopic cholecystectom y in the extrem ely eld erly. Surg Endosc d u ct inju ries follow ing lap aroscop ic cholecystectom y: an au d it of
2001;15(7):700–705. 5913 cases. Br J Surg 1996;83(10):1356–1360.
6. Poggio JL, Rowland CM, Gores GJ, et al. A comparison of laparoscopic 32. Wright KD, Wellw ood JM. Bile d u ct inju ry d u ring lap aroscop ic chole-
and open cholecystectom y in patients w ith compensated cirrhosis and cystectom y w ithou t op erative cholangiograp hy. Br J Surg 1998;85(2):
symptomatic gallstone d isease. Surgery 2000;127(4):405–411. 191–194.
7. Polychronid is A, Botaitis S, Tsarou cha A, et al. Lap aroscop ic ch ole- 33. Flu m DR, Flow ers C, Veenstra DL. A cost-effectiveness analysis of
cystectom y in eld erly p atients. J Gastrointestin Liver Dis 2008;17(3): intraoperative cholangiography in the prevention of bile d uct injury
309–313. d u ring laparoscopic cholecystectom y. J Am Coll Surg 2003;196(3):
8. Puggioni A, Wong LL. A m etaanalysis of lap aroscop ic cholecystec- 385–393.
tom y in p atients w ith cirrhosis. J Am Coll Surg 2003;197(6):921–926. 34. Ohtani T, Kaw ai C, Shirai Y, et al. Intraop erative u ltrasonograp hy ver-
9. Roslyn JJ, Binns GS, H u ghes EF, et al. Op en cholecystectom y. A con- sus cholangiograp hy d uring laparoscop ic cholecystectom y: a
tem porary analysis of 42,474 p atients. Ann Surg 1993;218(2):129–137. prospective com p arative stu d y. J Am Coll Surg 1997;185(3):274–282.
10. Strasberg SM, H ertl M, Sop er N J. An analysis of the p roblem of biliary 35. Barku n JS, Barkun AN , Meakins JL; for The McGill Gallstone Treat-
injury during laparoscopic cholecystectomy. J Am Coll Surg 1995;180(1): m ent Grou p . Laparoscop ic versu s op en cholecystectom y: the Cana-
101–125. d ian experience. Am J Surg 1993;165(4):455–458.
11. Flu m DR, Chead le A, Prela C, et al. Bile d u ct inju ry d u ring cholecys- 36. Barku n JS, Fried GM, Barku n AN , et al. Cholecystectom y w ithou t
tectom y and su rvival in m ed icare beneficiaries. JAMA 2003;290(16): op erative cholangiograp hy. Im p lications for com m on bile d u ct inju ry
2168–2173. and retained com m on bile d u ct stones. Ann Surg 1993;218(3):371–377;
12. N uzzo G, Giu liante F, Giovannini I, et al. Bile d u ct injury d u ring d iscu ssion 377–379.
laparoscopic cholecystectom y: results of an Italian national survey on 37. H olm in T, Jönsson B, Lingren B, et al. Selective or rou tine intraop era-
56 591 cholecystectom ies. Arch Surg 2005;140(10):986–992. tive cholangiograp hy: a cost-effectiveness analysis. World J Surg 1980;
13. Waage A, N ilsson M. Iatrogenic bile d u ct inju ry: a p op u lation-based 4(3):315–322.
stu d y of 152 776 cholecystectom ies in the Sw ed ish Inp atient Registry. 38. Livingston EH . Intraop erative cholangiograp hy and risk of com m on
Arch Surg 2006;141(12):1207–1213. bile d u ct inju ry. JAMA 2003;290(4):459; au thor rep ly 459–460.
39. Livingston EH , Miller JA, Coan B, et al. Costs and u tilization of intra- 62. Christoforid is E, Gou lim aris I, Tsalis K, et al. The end oscop ic m anage-
operative cholangiograp hy. J Gastrointest Surg 2007;11(9):1162–1167. m ent of persistent bile leakage after lap aroscopic cholecystectom y.
40. Sanjay P, Fulke JL, Exon DJ. ‘Critical view of safety’ as an alternative Surg Endosc 2002;16(5):843–846.
to routine intraoperative cholangiography d uring laparoscopic chole- 63. Lillem oe KD, Petrofski JA, Choti MA, et al. Isolated right segm ental
cystectom y for acu te biliary p athology. J Gastrointest Surg 2010;14(8): hepatic d u ct inju ry: a d iagnostic and therap eu tic challenge. J Gastroin-
1280–1284. test Surg 2000;4(2):168–177.
41. Sanjay P, Kulli C, Polignano FM, et al. Op tim al su rgical techniqu e, u se 64. Gronroos JM. Unsu ccessfu l end oscop ic stenting in iatrogenic bile d u ct
of intra-operative cholangiograp hy (IOC), and m anagem ent of acu te inju ry: rem em ber rend ezvou s p roced u re. Surg Laparosc Endosc Percu-
gallblad d er d isease: the resu lts of a nation-w id e su rvey in the UK and tan Tech 2007;17(3):186–189.
Ireland . Ann R Coll Surg Engl 2010;92(4):302–306. 65. Agarw al N, Sharma BC, Garg S, et al. End oscopic management of post-
42. Massarw eh N N , Devlin A, Elrod JA, et al. Su rgeon know led ge, behav- operative bile leaks. Hepatobiliary Pancreat Dis Int 2006;5(2):273–277.
ior, and op inions regard ing intraop erative cholangiograp hy. J Am Coll 66. Dow sett JF, Vaira D, H atfield AR, et al. End oscop ic biliary therap y
Surg 2008;207(6):821–830. u sing the com bined percu taneou s and end oscop ic techniqu e. Gas-
43. De Waele E, Op d e Beeck B, De Waele B, et al. Magnetic resonance troenterology 1989;96(4):1180–1186.
cholangiopancreatograp hy in the preoperative assessm ent of patients 67. Wallace M, Mid d lebrook M. Percu taneou s biliary reconstru ction: a
w ith biliary pancreatitis. Pancreatology 2007;7(4):347–351. report of tw o cases utilizing “blunt” recanalization and “rend ezvou s”
44. Mofid i R, Lee AC, Mad havan KK, et al. The selective u se of m agnetic techniqu es. Cardiovasc Intervent Radiol 2001;24(5):339–342.
resonance cholangiop ancreatograp hy in the im aging of the axial bil- 68. Waym an J, Mansfield JC, Matthew son K, et al. Com bined p ercu ta-
iary tree in p atients w ith acu te gallstone p ancreatitis. Pancreatology neou s and end oscopic proced ures for bile d uct obstruction: sim ulta-
2008;8(1):55–60 neou s and d elayed techniqu es com p ared . Hepatogastroenterology 2003;
45. Biffl WL, Moore EE, Offner PJ, et al. Rou tine intraop erative lap aro- 50(52):915–918.
scop ic u ltrasonograp hy w ith selective cholangiograp hy red u ces bile 69. Mercad o MA, Chan C, Orozco H , et al. To stent or not to stent bilioen-
d u ct com plications d u ring lap aroscop ic cholecystectom y. J Am Coll teric anastom osis after iatrogenic inju ry: a d ilem m a not answ ered ?
Surg 2001;193(3):272–280. Arch Surg 2002;137(1):60–63.
46. H u blet A, Dili A, Lem aire J, et al. Lap aroscopic u ltrasonograp hy as a 70. Johnson SR, Koehler A, Pennington LK, et al. Long-term resu lts of
good alternative to intraop erative cholangiograp hy (IOC) d uring su rgical rep air of bile d u ct inju ries follow ing lap aroscop ic cholecys-
lap aroscopic cholecystectom y: resu lts of p rosp ective stu d y. Acta Chir tectom y. Surgery 2000;128(4):668–677.
Belg 2009;109(3):312–316. 71. Cam eron JL, Gayler BW, Zu id em a GD. The u se of silastic transhep atic
47. Machi J, Johnson JO, Deziel DJ, et al. The routine u se of lap aroscop ic stents in benign and m alignant biliary strictu res. Ann Surg 1978;188(4):
u ltrasou nd d ecreases bile d u ct inju ry: a m u lticenter stu d y. Surg 552–561.
Endosc 2009;23(2):384–388. 72. H ep p J, Cou inau d C. Ap proach to and u se of the left hep atic d u ct in
48. Machi J, Oishi AJ, Tajiri T, et al. Rou tine lap aroscop ic u ltrasound can reparation of the com m on bile d u ct [in French]. Presse Med 1956;64(41):
significantly red u ce the need for selective intraop erative cholangiog- 947–948.
raphy d uring cholecystectom y. Surg Endosc 2007;21(2):270–274. 73. Couinaud C. Exposure of the left hepatic duct through the hilum or in the
49. Tranter SE, Thom pson MH . A p rosp ective single-blind ed controlled umbilical of the liver: anatomic limitations. Surgery 1989;105(1):21–27.
stu d y com p aring lap aroscop ic u ltrasou nd of the com m on bile d u ct 74. H ep p J. H ep aticojejunostom y u sing the left biliary tru nk for iatro-
w ith op erative cholangiograp hy. Surg Endosc 2003;17(2):216–219. genic biliary lesions: the French connection. World J Surg 1985;9(3):
50. Machi J, Tateishi T, Oishi AJ, et al. Lap aroscop ic u ltrasonograp hy ver- 507–511.
su s op erative cholangiograp hy d u ring lap aroscop ic cholecystectom y: 75. Voyles CR, Blu m gart LH . A techniqu e for the constru ction of high bil-
review of the literatu re and a com p arison w ith op en intraop erative iary–enteric anastom oses. Surg Gynecol Obstet 1982;154(6):885–887.
u ltrasonograp hy. J Am Coll Surg 1999;188(4):360–367. 76. Mercad o MA, Orozco H , d e la Garza L, et al. Biliary d u ct inju ry: p ar-
51. Stew art L, Way LW. Bile d u ct inju ries d u ring lap aroscop ic cholecys- tial segm ent IV resection for intrahep atic reconstru ction of biliary
tectom y. Factors that influ ence the resu lts of treatm ent. Arch Surg lesions. Arch Surg 1999;134(9):1008–1010.
1995;130(10):1123–1128; d iscu ssion 1129. 77. Schm id t SC, Settm acher U, Langrehr JM, et al. Managem ent and ou t-
52. Wood s MS, Traverso LW, Kozarek RA, et al. Characteristics of biliary com e of patients w ith com bined bile d u ct and hepatic arterial injuries
tract com p lications d u ring lap aroscop ic cholecystectom y: a m u lti- after lap aroscop ic cholecystectom y. Surgery 2004;135(6):613–618.
institutional stud y. Am J Surg 1994;167(1):27–33; d iscu ssion 33–34. 78. Gu pta N , Solom on H , Fairchild R, et al. Managem ent and ou tcom e of
53. Mercad o MA, Chan C, Jacinto JC, et al. Volu ntary and involu ntary lig- patients w ith com bined bile d u ct and hep atic artery inju ries. Arch
atu re of the bile d u ct in iatrogenic inju ries: a nonad visable ap p roach. J Surg 1998;133(2):176–181.
Gastrointest Surg 2008;12(6):1029–1032. 79. Koffron A, Ferrario M, Parsons W, et al. Failed p rim ary m anagem ent
54. Sicklick JK, Cam p MS, Lillem oe KD, et al. Su rgical m anagem ent of of iatrogenic biliary inju ry: incid ence and significance of concom itant
bile d u ct injuries su stained d u ring lap aroscop ic cholecystectom y: hepatic arterial d isrup tion. Surgery 2001;130(4):722–728; d iscu ssion
p eriop erative resu lts in 200 p atients. Ann Surg 2005;241(5):786–792; 728–731.
d iscu ssion 793–795. 80. Melton GB, Lillem oe KD, Cam eron JL, et al. Major bile d u ct inju ries
55. Lillem oe KD, Martin SA, Cam eron JL, et al. Major bile d u ct inju ries associated w ith lap aroscopic cholecystectom y: effect of su rgical rep air
d u ring laparoscopic cholecystectom y. Follow -u p after com bined su r- on qu ality of life. Ann Surg 2002;235(6):888–895.
gical and rad iologic m anagem ent. Ann Surg 1997;225(5):459–468; d is- 81. Schm id t SC, Langrehr JM, H intze RE, et al. Long-term resu lts and risk
cu ssion 468–471. factors influencing ou tcom e of m ajor bile d uct injuries follow ing
56. Du ca S, Bãlã O, Al-H ajjar N , et al. Lap aroscop ic cholecystectom y: inci- cholecystectom y. Br J Surg 2005;92(1):76–82.
d ents and com plications. A retrosp ective analysis of 9542 consecutive 82. Moraca RJ, Lee FT, Ryan JA Jr, et al. Long-term biliary fu nction after
lap aroscopic operations. HPB (Oxford) 2003;5(3):152–158. reconstru ction of m ajor bile d u ct inju ries w ith hep aticod u od enos-
57. H orton M, Florence MG. Unu su al abscess p atterns follow ing d ropp ed tom y or hepaticojeju nostom y. Arch Surg 2002;137(8):889–893; d iscu s-
gallstones during laparoscopic cholecystectom y. Am J Surg 1998;175(5): sion 893–894.
375–379. 83. Bonnel DH , Ligu ory CL, Lefebvre JF, et al. Placem ent of m etallic
58. Khalid M, Rashid M. Gallstone abscess: a d elayed com p lication of stents for treatm ent of p ostop erative biliary strictu res: long-term ou t-
sp illed gallstone after lap aroscop ic cholecystectom y. Emerg Radiol com e in 25 patients. AJR Am J Roentgenol 1997;169(6):1517–1522.
2009;16(3):227–229. 84. van Boeckel PG, Vleggaar FP, Siersem a PD. Plastic or m etal stents for
59. Mercad o MA, Chan C, Salgad o-N esm e N , et al. Intrahep atic rep air of benign extrahep atic biliary strictu res: a system atic review. BMC Gas-
bile d uct inju ries. A com p arative stu d y. J Gastrointest Surg 2008;12(2): troenterol 2009;9:96.
364–368. 85. Lezoche E, Paganini AM. Technical consid erations and lap aroscop ic
60. Winslow ER, Fialkow ski EA, Linehan DC, et al. “Sid ew ays”: results of bile d u ct exp loration: transcystic and choled ochotom y. Semin Laparosc
repair of biliary injuries using a policy of sid e-to-sid e hepatico- Surg 2000;7(4):262–278.
jejunostom y. Ann Surg 2009;249(3):426–434. 86. Soltan H M, Kow L, Toou li J. A sim p le scoring system for p red icting
61. Cou inaud C. Stu d ies on intrahep atic bile d u cts. J Chir (Paris) 1954; bile d uct stones in p atients w ith cholelithiasis. J Gastrointest Surg 2001;
70(4):310–328. 5(4):434–437.
87. H eili MJ, Wintz N K, Fow ler DL. Choled ocholithiasis: end oscop ic ver- 111. Z’Graggen K, Birrer S, Mau rer CA, et al. Incid ence of p ort site recu r-
sus lap aroscopic m anagem ent. Am Surg 1999;65(2):135–138. rence after lap aroscop ic cholecystectom y for p reop eratively u nsu s-
88. H erm ann RE. The sp ectru m of biliary stone d isease. Am J Surg 1989; p ected gallblad d er carcinom a. Surgery 1998;124(5):831–838.
158(3):171–173. 112. Sarli L, Contini S, Sansebastiano G, et al. Does lap aroscop ic cholecys-
89. H ou d art R, Perniceni T, Darne B, et al. Pred icting com m on bile d u ct tectom y w orsen the prognosis of unsu spected gallblad d er cancer?
lithiasis: d eterm ination and prosp ective valid ation of a m od el pred ict- Arch Surg 2000;135(11):1340–1344.
ing low risk. Am J Surg 1995;170(1):38–43. 113. Su zuki K, Kim u ra T, Ogaw a H . Is lap aroscop ic cholecystectom y haz-
90. Martin DJ, Vernon DR, Toou li J. Su rgical versu s end oscopic treatm ent ard ou s for gallblad d er cancer? Surgery 1998;123(3):311–314.
of bile d u ct stones. Cochrane Database Syst Rev 2006;(2):CD003327. 114. Su zuki K, Kim u ra T, Ogaw a H . Long-term p rognosis of gallblad d er
91. Cuschieri A, Croce E, Faggioni A, et al. EAES d uctal stone study. Pre- cancer d iagnosed after lap aroscop ic cholecystectom y. Surg Endosc
liminary findings of multi-center prospective randomized trial com par- 2000;14(8):712–716.
ing two-stage vs single-stage management. Surg Endosc 1996;10(12): 115. Greene FL, Page DL, Flem ing ID, et al. AJCC cancer staging manual, 6th
1130–1135. ed . N ew York: Sp ringer; 2002:xiv, 421.
92. Poon RT, Liu CL, Lo CM, et al. Managem ent of gallstone cholangitis in 116. Fong Y, Jarnagin W, Blu m gart LH . Gallblad d er cancer: com p arison of
the era of lap aroscop ic cholecystectom y. Arch Surg 2001;136(1):11–16. p atients p resenting initially for d efinitive operation w ith those pre-
93. Su c B, Escat J, Cherqu i D, et al. Su rgery vs end oscop y as prim ary senting after prior noncu rative intervention. Ann Surg 2000;232(4):
treatm ent in sym ptom atic patients w ith susp ected com m on bile d u ct 557–569.
stones: a m u lticenter rand om ized trial. French Associations for Su rgi- 117. Paw lik TM, Gleisn er AL, Vigano L, et al. In cid ence of fin d in g resid -
cal Research. Arch Surg 1998;133(7):702–708. u al d isease for in cid ental gallblad d er carcin om a: im p lication s for
94. Byrne MF, McLou ghlin MT, Mitchell RM, et al. For p atients w ith p re- re-resection. J Gastrointest Surg 2007;11(11):1478–1486; d iscu ssion
d icted low risk for choled ocholithiasis u nd ergoing lap aroscop ic 1486–1487.
cholecystectom y, selective intraop erative cholangiograp hy and post- 118. d e Aretxabala X, Roa I, Bu rgos L, et al. Gallblad d er cancer in Chile. A
operative end oscop ic retrograd e cholangiop ancreatograp hy is an rep ort on 54 potentially resectable tu m ors. Cancer 1992;69(1):60–65.
effective strategy to lim it u nnecessary p roced u res. Surg Endosc 2009; 119. Wakai T, Shirai Y, Yokoyam a N , et al. Early gallblad d er carcinom a
23(9):1933–1937. d oes not w arrant rad ical resection. Br J Surg 2001;88(5):675–678.
95. Cotton PB, Garrow DA, Gallagher J, et al. Risk factors for com p lica- 120. You DD, Lee H G, Paik KY, et al. What is an ad equ ate extent of resec-
tions after ERCP: a m u ltivariate analysis of 11,497 p roced u res over 12 tion for T1 gallblad d er cancers? Ann Surg 2008;247(5):835–838.
years. Gastrointest Endosc 2009;70(1):80–88. 121. H u em an MT, Vollm er CM Jr, Paw lik TM. Evolving treatm ent strate-
96. Ryan ME. ERCP com p lication rates: how low can w e go? Gastrointest gies for gallblad d er cancer. Ann Surg Oncol 2009;16(8):2101–2115.
Endosc 2009;70(1):89–91. 122. Welling TH , H eid t DG, Englesbe MJ, et al. Biliary com p lications fol-
97. N athanson LK, O’Rou rke N A, Martin IJ, et al. Postop erative ERCP low ing liver transp lantation in the m od el for end -stage liver d isease
versu s lap aroscop ic choled ochotom y for clearance of selected bile era: effect of d onor, recip ient, and technical factors. Liver Transpl 2008;
d u ct calcu li: a rand om ized trial. Ann Surg 2005;242(2):188–192. 14(1):73–80.
98. Rhod es M, Su ssm an L, Cohen L, et al. Rand om ised trial of lap aro- 123. N ealon WH , Urru tia F. Long-term follow -u p after bilioenteric anasto-
scop ic exp loration of com m on bile d u ct versu s p ostop erative end o- m osis for benign bile d u ct strictu re. Ann Surg 1996;223(6):639–645;
scop ic retrograd e cholangiograp hy for com m on bile d u ct stones. d iscu ssion 645–648.
Lancet 1998;351(9097):159–161. 124. Am m ori JB, Mu lholland MW. Ad u lt typ e I choled ochal cyst resection.
99. Berd ah SV, Orsoni P, Bege T, et al. Follow -u p of selective end oscop ic J Gastrointest Surg 2009;13(2):363–367.
ultrasonograp hy and / or end oscop ic retrograd e cholangiograp hy 125. Koornstra JJ, Fry L, Mönkem ü ller K. ERCP w ith the balloon-assisted
prior to laparoscop ic cholecystectom y: a p rosp ective stu d y of 300 enteroscop y techniqu e: a system atic review. Dig Dis 2008;26(4):
patients. Endoscopy 2001;33(3):216–220. 324–329.
100. Petrov MS, Savid es TJ. System atic review of end oscop ic u ltrasonogra- 126. Finley DS, H inojosa MW, Paya M, et al. H ep atic artery p seu d oa-
phy versus end oscop ic retrograd e cholangiop ancreatograp hy for su s- neu rysm : a rep ort of seven cases and a review of the literatu re. Surg
pected choled ocholithiasis. Br J Surg 2009;96(9):967–974. Today 2005;35(7):543–547.
101. Lee YT, Chan FK, Leu ng WK, et al. Com p arison of EUS and ERCP in 127. al-Jerou d i A, Belli AM, Shorvon PJ. False aneu rysm of the p ancreati-
the investigation w ith susp ected biliary obstru ction cau sed by chole- cod uod enal artery com plicating therapeutic end oscopic retrograd e
d ocholithiasis: a rand om ized stu d y. Gastrointest Endosc 2008;67(4): cholangiop ancreatograp hy. Br J Radiol 2001;74(880):375–377.
660–668. 128. Cantw ell CP, Pena CS, Gervais DA, et al. Thirty years’ exp erience w ith
102. Liu CL, Fan ST, Lo CM, et al. Com p arison of early end oscopic ultra- balloon d ilation of benign p ostop erative biliary strictu res: long-term
sonograp hy and end oscop ic retrograd e cholangiop ancreatograp hy in outcom es. Radiology 2008;249(3):1050–1057.
the m anagem ent of acute biliary pancreatitis: a p rospective rand om - 129. Savad er SJ, Trerotola SO, Merine DS, et al. H em obilia after p ercu ta-
ized stu d y. Clin Gastroenterol Hepatol 2005;3(12):1238–1244. neous transhepatic biliary d rainage: treatm ent w ith transcatheter
103. Led ro-Cano D. Su sp ected choled ocholithiasis: end oscop ic u ltrasound em bolotherap y. J Vasc Interv Radiol 1992;3(2):345–352.
or m agnetic resonance cholangio-pancreatograp hy? A system atic 130. Kocher M, Cerná M, H avlík R, et al. Percu taneou s treatm ent of benign
review. Eur J Gastroenterol Hepatol 2007;19(11):1007–1011. bile d u ct strictu res. Eur J Radiol 2007;62(2):170–174.
104. Snow LL, Weinstein LS, H annon JK, et al. Managem ent of bile d uct 131. Millis JM, Tom pkins RK, Zinner MJ, et al. Managem ent of bile d u ct
stones in 1572 p atients u nd ergoing lap aroscop ic cholecystectom y. Am strictu res. An evolving strategy. Arch Surg 1992;127(9):1077–1082; d is-
Surg 1999;65(6):530–545; d iscu ssion 546–547. cu ssion 1082–1084.
105. Cu schieri A, Ad am son GD. Mu ltim ed ia article. Lap aroscop ic transec- 132. Saad WE, Saad N E, Davies MG, et al. Transhep atic balloon d ilation of
tion choled ochod u od enostom y. Surg Endosc 2005;19(5):728. anastom otic biliary strictures in liver transplant recipients: the signifi-
106. Khalid K, Shafi M, Dar H M, et al. Choled ochod u od enostom y: reap - can ce of a p aten t h ep atic artery. J Vasc Interv Radiol 2005;16(9):
praisal in the lap aroscop ic era. ANZ J Surg 2008;78(6):495–500. 1221–1228.
107. Panis Y, Fagniez PL, Brisset D, et al.; for The French Association for 133. Lee BH , Choe DH , Lee JH , et al. Metallic stents in m alignant biliary
Surgical Research. Long term resu lts of choled ochod u od enostom y obstru ction: prospective long-term clinical resu lts. AJR Am J Roentgenol
versu s choled ochojeju nostom y for choled ocholithiasis. Surg Gynecol 1997;168(3):741–745.
Obstet 1993;177(1):33–37. 134. N eu haus H , H agenm ü ller F, Griebel M, et al. Percu taneou s cholangio-
108. Jem al A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J scop ic or transp ap illary insertion of self-exp and ing biliary m etal
Clin 2008;58(2):71–96. stents. Gastrointest Endosc 1991;37(1):31–37.
109. Steinert R, N estler G, Sagynaliev E, et al. Lap aroscop ic cholecystec- 135. Lopez RR Jr, Cosenza CA, Lois J, et al. Long-term resu lts of m etallic
tom y and gallblad d er cancer. J Surg Oncol 2006;93(8):682–689. stents for benign biliary strictu res. Arch Surg 2001;136(6):664–669.
o
110. Paolu cci V, Schaeff B, Schneid er M et al. Tu m or seed ing follow ing 136. Petrtyl J, Brf uha R, H orák L, et al. Managem ent of benign intrahep atic
laparoscop y: international su rvey. World J Surg 1999;23(10):989–995; bile d u ct strictu res: initial exp erience w ith p olyd ioxanone biod egrad -
d iscussion 996–967. able stents. Endoscopy 42(Su p p l 2):E89–E90.
CHAPTER
36
Complications of Pancreatic Surgery

Diane M. Simeone
■ INTRODUCTION allow ed a m ore p recise d ocu m entation of the natu ral his-
tory of p ancreatic p seu d ocysts. Tw o large rep orts in the
Surgical d iseases of the pancreas are often m ore d ifficu lt to early 1990s (1,2) d ocu m ented the safety of conservative
treat than those of other abd om inal viscera. The p ancreas management of asym ptom atic pancreatic pseu d ocysts
lies hid d en w ithin the recesses of the retroperitoneum , and w ith carefu l clinical and rad iograp hic follow -u p , w ith the
d u ring lap arotom y, it is not easily visu alized w ithou t need for intervention lim ited to patients w ith persistent
extensive m obilization and d issection. The d ifficu lt loca- symp tom s related to the p seu d ocyst (p ain, im p aired gastric
tion of the p ancreas gland , w ith its intim ate association emptying) or pseud ocyst-related complications. Pseud ocyst-
w ith other vital stru ctures that su rround it, ad d s to the related com p lications inclu d e infection, hem orrhage, ru p -
com plexity of p ancreatic surgery. Resection of the pancreas tu re, and obstru ction of the gastrointestinal tract. Surgical
is consid ered a m ajor op erative p roced u re that can be asso- op tions for the m anagem ent of p ancreatic p seu d ocysts
ciated w ith significant m orbid ity and m ortality. In this inclu d e internal d rainage, p seu d ocyst excision, and exter-
chapter, com p lications in operative proced ures involving nal d rainage (Table 36.1). Recent stu d ies have d em on-
the pancreas w ill be d iscussed , along w ith m anagem ent strated that in select p atients, lap aroscop ic and end oscopic
strategies to ad d ress sp ecific com plications that arise. d rainage m ay be u tilized to treat the p seu d ocyst. With all
of these ap p roaches, a frozen section biop sy of the w all of
■ COMPLICATIONS OF OPERATIVE PROCEDURES the p seu d ocyst shou ld be inclu d ed as p art of the op erative
p roced u re to exclu d e the p ossibility of a cystic neoplasm ,
■ Drainage of pancreatic pseudocysts w hich has an ep ithelial lining. If the cyst has an ep ithelial
lining, it p robably rep resents a neop lastic cyst (or in rare
Introduction
situ ations, a sim p le cyst or d u p lication cyst). N eoplastic
A pancreatic p seu d ocyst is a localized collection of p ancre- cysts shou ld be consid ered for su rgical resection if they are
atic juice enclosed by a w all of fibrou s or granulation tissu e, sym p tom atic or p ossess concerning featu res for m alig-
arising as a consequ ence of acute or chronic pancreatitis, nancy (solid com p onent, size greater than 3 centim eters,
neoplastic obstru ction of the pancreatic d uct, or pancreatic d ilated p ancreatic or biliary d u ct) as d efined by the Send ai
trau m a. It is imp ortant to d ifferentiate pseu d ocysts from consensu s conference gu id elines (3).
acu te flu id collections that form early in the cou rse of acu te
p ancreatitis, w hich can occu r in up to 40% of cases. These Internal Drainage Procedures
acu te flu id collections lack a w all of fibrou s or granulation Internal d rainage is the preferred surgical app roach for
tissu e, are likely a seriou s reaction to p ancreatic inflam m a- u ncom plicated pseud ocysts requiring operative interven-
tion, and u su ally resolve spontaneou sly w ithou t any tion. Most cyst w alls w ill m atu re w ithin 6 w eeks of the
d irected intervention. The d evelopm ent of a pancreatic onset of sym p tom s. Enteric d rainage of the p seu d ocyst into
p seu d ocyst shou ld be su spected in any patient w ith a bou t the stom ach, d u od enu m , or jeju nu m is p ossible w ith the
of acu te p ancreatitis follow ed by a prolonged recovery choice of d rainage p roced u re based on the location of the
from the ep isod e. A com puted tom ograp hy (CT) scan can p seu d ocyst.
be perform ed to confirm the p resence of pancreatic inflam -
m ation. Su rgical d ogm a in the past w as to treat any Cystgastrostomy. Cystgastrostom y shou ld be p erform ed
p seu d ocyst that p ersisted beyond 6 w eeks w ith op erative w hen the pseudocyst is firmly adherent to the posterior w all
intervention becau se they w ere believed to have a low like- of the stomach (Fig. 36.1). This approach is a faster and less
lihood of resolu tion and a high frequ ency of com p lications. technically d em and ing than d rainage into the d uod enum or
The ad vent of m ore routine u se of CT scanning in the 1970s jeju num. An excep tion to this approach may be mad e w ith
giant ( 15 cm) p seud ocysts. A higher failure rate w ith cyst-
gastrostom y has been noted in these patients probably be-
Diane M. Simeone: University of Michigan Medical Center, cause cystgastrostomy may not provid e d epend ent d rainage
Ann Arbor, Michigan 48015. of the large cyst cavity (4). A cystjejunostomy may be more
450
Chapter 36 • Complications of Pancreatic Surgery 451
Table 3 6 .1 Su r gica l op t ion s t o t r ea t p seu d ocyst s significant m orbid ity if an anastom otic leak and resu ltant
d u od enal fistu la ensu es, and therefore it is a less d esirable
Internal drainage p roced u re to p erform .
Cystgastrostomy
Cystjejunostomy
Laparoscopic Management of Pancreatic Pseudocysts. There
Cystduodenostomy
are no large p u blished series on the u se of lap aroscop y to
Pseudocyst excision treat p an creatic p seu d ocysts. Several sm all series h ave
External drainage rep orted good resu lts an d m in im al m orbid ity w ith la-
p aroscop ic cystgastrostomy or cystjejunostomy (5–7). This
approach shou ld cu rrently be limited to su rgeons w ho are
highly experienced in advanced laparoscopic techniques. The
appropriate in this setting. Important components of the op-
frequency of a laparoscopic approach to pseudocyst treatment
eration to optimize success are to (a) ensure that the pseud o-
will continue to increase in the future.
cyst is ad herent to the stom ach to m inim ize risk of leakage
at the anastom osis—this should be evid ent by anterior d is-
Alternatives to Surgical Therapy
placem ent of the back w all of the stom ach and confirm ed
by need le asp iration; (b) create a w id e, 4 to 5 cm op ening Percutaneous Drainage. Percutaneous d rainage of pancreatic
betw een the p seu d ocyst and posterior w all of the stom ach p seu d ocysts has been reported as an alternative to surgical
to facilitate d rainage; (c) rem ove all d ebris present w ithin treatment for over tw o d ecad es. Simple percu taneous aspi-
the p seu d ocyst cavity; and (d ) ensu re hem ostasis by p er- ration may be ind icated to samp le p seu d ocyst flu id if there
form ing a continuous, locking closu re of the su tu re line. is a clinical concern of pseud ocyst infection. Aspiration w ith-
out d rain p lacem ent as p rimary therapy to treat p ancreatic
Cystjejunostomy. Cystjeju nostom y is a versatile techniqu e p seu d ocysts has a low su ccess rate and is not ad vocated . As
that can u sed to internally d rain p seu d ocysts that are loan alternative to su rgical d rainage, p ercu taneou s catheter
cated in a variety of locations, ow ing to the m obility of the d rainage has been su pp orted by m any group s for treatm ent
jeju nal lim b. For cysts d rained into the jeju nu m , a 60 cm of symp tomatic p seu d ocysts, w ith initial rep orts tou ting a
long Rou x-en-Y lim b is u sed . A tw o-layer anastom osis is 70% to 90% su ccess rate (8–10). There has not been a ran-
perform ed on the m ost d epend ent part of the cyst so that d om ized , prospective stud y com paring the resu lts of percu-
d rainage w ill be com plete and facilitate rapid obliteration taneou s d rainage to op erative d rainage of p seu d ocysts.
of the cyst cavity. Several retrosp ective stu d ies exam ining the long-term re-
su lts of percu taneou s catheter d rainage have reported less
Cystduodenostomy. Cystd u od enostom y is p erform ed infre- favorable long-term resu lts, w ith long-term su ccess rates
qu ently, and its u se is lim ited to pseud ocysts in the head or ranging from 21% to 60% (11–13). Percu taneou s catheter
uncinate p rocess of the pancreas that lie w ithin 1 cm of the d rainage may be a useful technique for treatment of infected
d u od enal lu m en. The p roced u re can be associated w ith p ancreatic pseu d ocysts if there is no other ind ication for la-
p arotom y. Com p lications associated w ith p ercu taneou s
catheter drainage include creation of a pancreatic fistula and
the inability to com p letely evacu ate a cyst, both of w hich
m ay u ltim ately requ ire op erative intervention. The likeli-
hood of a persistent pancreatic fistula is increased in patients
in w hom the pseud ocyst has a d irect communication w ith
the p ancreatic d uct (14).
Endoscopic Drainage. Endoscopic approaches have also been

reported as treatm ent options for p atients w ith pancreatic
p seu d ocysts. One ap p roach, transm u ral d rainage, has been
u tilized for pseu d ocysts ad herent to the w all of either the
d u od enu m or stom ach. Tw o p rerequ isites for attem p ting
this form of treatm ent are bu lging d u e to the cyst shou ld be
obviou s on u p p er end oscop y and the d istance betw een the
cyst and lumen should not exceed 1 cm. Using the Seld inger
technique, the cyst is cannulated w ith a guid ew ire, follow ed
by stent p lacem ent. A second end oscop ic ap p roach,
transpapillary (transam pullary) d rainage, has been utilized
in selected p atients to d rain p seu d ocysts d irectly into the
p ancreatic d u ct. To u se this ap p roach, the p seud ocyst m ust
FIGURE 36.1. Large pancreatic pseudocyst adherent to the posterior wall d irectly com m u nicate w ith the p ancreatic d u ct. A stent is
of the stomach. p laced and left for 6 to 8 w eeks or u ntil CT exam ination
d em onstrates resolu tion of the p seu d ocyst. While the re- Bleeding. Hemorrhage occurs following internal drainage of
p orted su ccess rates w ith both ap p roaches are favorable, pancreatic pseud ocysts in 2% to 16% of patients (2,12,13). He-
there is a relatively high bleed ing and p erforation rate morrhage following an internal drainage procedure may be
(15,16). due to bleeding at a suture line, and if bleeding occurs in the
immediate postoperative period, it should be treated by re-
Complications of Surgical Drainage exploration. Alternatively, patients may have erosion of a pan-
Mortality. The mortality rate following internal drainage p ro- creatic pseudocyst into adjacent vessels, which can result in
ced ure ranges from 0% to 13% w ith several recent series re- massive hem orrhage. The splenic artery is most com monly
porting a 0% m ortality rate (12–14). involved (45%), follow ed by the gastrod uod enal (18%) and
pancreaticod uodenal (18%) arteries (17). In this setting, selec-
Recurrence tive visceral angiography should be performed, with angio-
The recurrence rate follow ing internal drainage of pseudo- graphic embolization using coils or pledgets usually resulting
cysts ranges from 0% to 15% (12–14). Pseud ocysts m ight in definitive therapy (18,19) (Fig. 36.2). Surgery should be re-
recu r follow ing internal d rainage ow ing to several reasons. served for patients w ho are hemod ynamically unstable or
If an in ad equ ately sized op ening ( 4 cm ) has been cre- have failed embolization procedures. Peripancreatic inflam-
ated betw een the stom ach, jejunu m , or d uod enum and the mation and postoperative changes may make operative con-
pseudocyst cavity, a pseudocyst may recur. This is a technical trol d ifficult. Initial control of bleeding may be obtained by
complication that can be easily avoided. Inadequate drainage digital compression of the bleed ing vessel or packing of the
of multiple pseud ocysts may be a cause of persistent abd om- pseudocyst. Surgical approaches for d efinitive treatment in-
inal pain or recurrence. Ad d itionally, a cyst m ay recu r if it is clu d e p roxim al and d istal arterial ligation com bined w ith
a cystic neoplasm that w as mistaken for a pseud ocyst, high- intracystic suture ligation, distal pancreatectomy, and splenec-
lighting the need to send a frozen section of the pseu d ocyst tomy for bleed ing arising from the body and tail of the pan-
w all to confirm the absence of an epithelial lining. creas, or in rare cases, pancreaticoduodenectomy (18–20).
A B
FIGURE 36.2. A: CT scan of a pancreatic pseudocyst

with intravenous contrast within the pseudocyst, demon-
strating active hemorrhage. B: Visceral angiogram docu-
menting a pseudoaneurysm of the gastroduodenal artery.
C C: Postembolization angiogram depicting successful coil
embolization of the pseudoaneurysm.
External Drainage
External d rainage of pancreatic pseud ocysts is ind icated
for pseud ocysts that are fou nd to be grossly infected or that
d o not have a m ature w all su fficient for anastom osis at the
tim e of exp loration. External d rainage is perform ed by
opening the p seu d ocyst, evacuating its contents, and
inserting a soft, silastic catheter into the pseu d ocyst cavity.
A p ancreaticocu taneou s fistula may d evelop follow ing the
external d rainage p roced ure. In m ost cases, these fistu las
w ill close sp ontaneou sly.
Special Consideration—Multiple Pseudocysts

Multiple pseud ocysts that require treatment m ay occasion-
ally be present. While pancreatic resection is an option (espe-
cially if the pseud ocysts are located in the tail of the gland ),
the preferred treatment is internal d rainage. This can per-
form ed by converting multiple cysts into one large cyst to be
used for a single anastomosis cystjejunostomy or combined
treatment w ith cystgastrostomy and cystjejunostomy. In all
cases, the surgeon should ensure that all cysts have been FIGURE 36.3. A CT scan of a patient with necrotizing pancreatitis with evi-
dence of extraluminal gas.
drained , using intraoperative ultrasound if needed .
techniqu e of repeated operative necrosectom y w ith closure

■ DRAINAGE OF INFECTED over d rains (26). A recent CT scan is u sed to gu id e surgical
PANCREATIC NECROSIS exp loration to ensu re that all areas of necrosis or flu id are
■ Introduction exp lored . Up on entering the abd om en, the lesser sac m ay
be entered throu gh the gastrocolic ligam ent or throu gh
While the majority of cases of acute pancreatitis are mild and the transverse m esocolon. Perip ancreatic necrotic tissue
self-lim iting, necrotizing pancreatitis d evelops in about 15% shou ld be rem oved blu ntly. Forcefu l or sharp d issection
of patients, w ith infection of pancreatic and peripancreatic shou ld be avoid ed , as this m ay resu lt in bleed ing or inju ry
necrosis representing the most important risk factor for a to the bow el. A sample of the necrotic tissue shou ld be sent
fatal outcom e. Infection of pancreatic necrosis typically for bacteriologic analysis. If flu id collections or necrosis
occurs in the second or third w eek after the onset of the d is- extend to the pararenal or retrocolic spaces, these should be
ease and should be suspected in any patient w ith a particu- opened and d ebrid ed . Extensive irrigation is then per-
larly severe bout of acute pancreatitis who develops form ed . If all necrotic d ebris has been rem oved , then the
multisystem organ d ysfunction and / or systemic signs of abd omen may be closed over d rains. If necrotic or question-
sepsis. In such patients, a d ynamic CT scan w ith intravenous ably viable tissue rem ains ad herent, then rep eated opera-
contrast should be obtained to d eterm ine if there is evid ence tive evalu ation shou ld be perform ed in 48 hours, and
of pancreatic necrosis, represented by areas of nonperfusion. further necrosectom y should be perform ed as outlined .
If there are obvious signs of infection, such as presence of This p rocess is rep eated as necessary until all necrotic tissue
extraluminal gas, surgical exploration and d ebridement are is removed , and the abd omen is closed over d rains. Soft
indicated (Fig. 36.3). Otherwise, patients should und ergo silastic d rains rather than firm su mp d rains should be used
CT-guid ed fine need le aspiration (FN A) w ith Gram stain to minimize the risk of pressu re inju ry to blood vessels and
and bacteriological cultures if infection of necrosis is clini- the bow el. Repeated exp loration m ay be facilitated by use
cally suspected . Infection of pancreatic necrosis as proven by of zipp er placement, w hich allow s easy, rap id entry into the
FN A is regard ed as an ind ication for surgical d ebrid ement. abd omen and p revents loss of abd ominal d omain (26).
The ind ications for surgical debridement of sterile pancre-
atic necrosis remain controversial (21–23). ■ Complications
Mortality
■ Operative technique In p atients w ith infected pancreatic necrosis m anaged
Infected pancreatic necrosis is an ind ication for operative w ithou t intervention, the m ortality rate ap p roaches 100%.
necrosectom y. Several ap proaches have been ad vocated , The m ortality rate in several recent series for p atients w ho
inclu d ing d ebrid ement w ith immed iate closure over d rains u nd ergo operative treatm ent of infected pancreatic necro-
(w ith or w ithout continuous lavage of the lesser sac), sis ranges from 6% to 25% (24–26), m orbid ity rates rem ain
d ebrid ement w ith open or semi-open packing, and staged high. The m anagem ent of p atients w ith infected pancreatic
d ebrid ement w ith closure over d rains. (21–25). We favor the necrosis is challenging, as these p atients often requiring
prolonged ICU care and lengthy hospital stays. Despite this, tissue (26). The d evelopment of an intra-abd ominal abscess
encou raging d ata from long-term follow u p of p atients w ho d oes not appear to have an effect on survival; mortality in
have recovered from p ancreatic d ebrid em ent reveal that these patients w as similar to that in other patients.
most of these patients are able to retu rn to norm al activity
and have a good qu ality of life (27). Fistulas
Pancreatic and gastrointestinal tract fistulas are common
Hemorrhage complications of surgical treatment of necrotizing pancreati-
H em orrhage requ iring som e form of active intervention tis. The pathogenesis of fistula formation in this setting
follow ing p ancreatic d ebrid em ent is reported to occu r in appears to be multifactorial. Perhaps the most common fac-
5% to 20% of p atients (22,25,26). H emorrhage can occu r tor in the development of fistulas is pancreatic parenchymal
d u ring the op erative proced u re or postoperatively, and necrosis, w hich results in d isruption of pancreatic d ucts w ith
may be second ary to general oozing from the d ebrid em ent extravasation of pancreatic juice into the retroperitoneum.
bed or d u e to d irect inju ry to nearby vascu lar stru ctu res, While this is clearly important in the d evelopment of pancre-
includ ing the sp lenic and portal veins or the splenic, su p e- atic fistulas, the enzymatic juices and inflammatory med ia-
rior m esenteric, inferior pancreatic, or mid d le colic arteries. tors produced as part of the necrotizing process may also
Gentle blu nt d issection d u ring d ebrid em ent and care to cause vascular thrombosis with resultant ischemia, which
place d rains aw ay from m ajor vessels are im portant in can lead to segmental necrosis of the bow el. Extravasated
d ecreasing the risk of hem orrhage. Direct su rgical control secretions may also directly result in necrosis of adjacent
in this setting is the stand ard approach, bu t angiograp hic segments of the gastrointestinal tract. Alternatively, the
em bolization is another option in selected p atients. d evelopment of fistulas may be iatrogenic, caused by
trauma to the surface of organs of the gastrointestinal tract,
Recurrent Intra-abdominal Abscess either second ary to d ebrid ement, repeated packing, or pres-
Recu rrent intra-abd om inal abscess is reported to d evelop in sure necrosis from an ad jacent d rain.
13% to 26% of p atients follow ing necrosectomy (24–26). The incid ence of p ancreatic fistu las ranges from 19%
Many of these patients can be successfully managed by sim- to 53% (25,26,28). Diagnosis is m ad e based on p ersisten t
ple, CT-gu id ed p ercu taneou s d rainage, w ith only a few d rainage w ith high am ylase concentration from d rains
patients requ iring re-operative d rainage. In one series u sing left in the lesser sac or by en d oscop ic retrograd e ch olan -
a strategy of p lanned re-operative necrosectomy w ith final giop ancreatograp hy (ERCP) (Fig. 36.4). Th e vast m ajority
closure over d rains, the incid ence of postoperative intra- of fistu las can be su ccessfu lly m an aged con servatively
abd om inal abscess w as increased in p atients w ho u nd er- w ith d rains left in th e su rgical site, w h ich are grad u ally
w ent few er re-op erative necrosectom ies, highlighting the ad vanced ou t. While som etim es u sed , it is u nclear
im p ortance of com p lete rem oval of all infected necrotic w h ether octreotid e facilitates fistu la closu re in these
A B
FIGURE 36.4. An endoscopic retrograde cholangiopancreatography (A) of a patient at 3 weeks following an operative debridement for
necrotizing pancreatitis demonstrating a pancreatic fistula (B).
Table 3 6 .2 M a n a gem en t of ga st roin t est in a l fi st u la s a ft er n ecrosect om y

(N 61 p a t ie n t s ) (d eve lop m e n t o f g a s t r o in t e s t in a l fi s t u la s
19 (31 %)
Number Spontaneous Closure Operative Treatment Required
Colonic 8 3 5
Duodenal 5 2 3
Enteric 4a 3 0
Gastric 2 2 0
a
One patient died of multisystem organ failure with a persistent, controlled fistula.
Data from Tsiotos GG, Smith CD, Sarr MG. Incidence and management of pancreatic and enteric fistulas after surgical management
of sever necrotizing pancreatitis. Arch Surg 1995;130:48–52.
p atien ts. In the sm all p ercentage of p atients that have a obstru ction and hyp ertension, w hich is thou ght to cau se
p ersistent, high -ou tp u t fistu la that fails to close w ith con- p ain. The rationale for this op eration is to relieve the d u ctal
servative m anagem ent, op erative treatm ent of the fistu la hyp ertension, and thu s p ain.
is requ ired , w hich m ay requ ire a p ancreaticojeju nostom y
or d istal p ancreatectom y. Operative Technique
Gastrointestinal fistulas, w hen they occur, can be d ifficult A lateral (longitud inal) pancreaticojejunostomy is the most
problems to manage, with the likelihood of spontaneous clo- effective d rainage proced ure. The proced ure involves a lon-
sure d epend ent on the fistula site (Table 36.2). Fistulae are gitud inal incision in the pancreas through the anterior wall
defined by a contrast study show ing direct communication of the main pancreatic d uct. The duct can usually be pal-
w ith the und erlying organ. In one report, tw o of tw o gastric pated as a soft, compressible area in an otherw ise firm gland .
fistulas, three of five d uod enal fistulas, three of four enteric Identification of the duct can be confirmed by need le aspira-
fistulas, and one of eight colonic fistulas closed sponta- tion of clear fluid. If there is any difficulty in duct identifica-
neously (28). The remaining fistulas required operative clo- tion, intraoperative ultrasound can be used . A Roux-en-Y
sure. Repair of d uod enal fistulas may be managed by limb of jejunum is then sutured to the opened duct along its
Roux-en-Y duodenojejunostomy, or if necessary by a pyloric length so that the pancreatic juice d rains d irectly into the
exclusion procedure, w hich consists of pyloric stapling w ith intestine. Ductal stones and d ebris are removed , if present.
a gastrojejunostomy. Enteric fistulas are usually corrected by The success rate of this procedure in relieving pain has been
segmental resection. Colonic fistulas may occasionally be evaluated in several large series and ranges from 60% to 90%
treated w ith segmental resection under ideal circumstances, (29–31). Factors contributing to the success of the operation
but frequently require proximal diversion. are d uct size ( 8 mm), and a lengthy ( 6 cm) pancreatic-
jejunal anastomosis, w hich extend s from the pancreatic tail
Endoscopic Approach to a point 1 centimeter from the d uod enum.
A number of reports have recently d escribed the successful
treatment of infected pancreatic necrosis using a translumi-
nal endoscopic approach. This approach is depend ent on the
availability of highly skilled ad vanced endoscopists w ho are
facile in the techniques required to und ertake these types of
procedures. As endoscopic necrosectomy becomes further
refined , additional studies w ill be needed to d efine its role in
relation to the surgical management of these patients.
■ LONGITUDINAL PANCREATICOJ EJ UNOSTOMY

■ Introduction
Longitu d inal p ancreaticojeju nostom y, or the Puestow p ro-
ced u re, is p erform ed to treat intractable pain in p atients
w ith chronic p ancreatitis w ho have p ancreatic d u ctal
d ilatation (Fig. 36.5). In patients w ith chronic pancreatitis,
d am age to acinar cells results in release of proteolytic
FIGURE 36.5. A CT scan of a patient with chronic pancreatitis with a history
of intractable abdominal pain. A markedly dilated pancreatic duct is evident,
enzym es into the d uct, w hich ind u ces protein plu g form a- making this patient a good candidate for a lateral pancreaticojejunostomy
tion and stone d evelopm ent. This p rocess prom otes d u ctal (Puestow procedure).
Complications p ap illary m u cinou s neop lasm s, islet cell tu m ors, sarcomas,

Mortality. Lateral pancreaticojejunostom y is a relatively safe or other rare tu m ors involving the p ancreatic head ,
proced u re, w ith m ost series reporting op erative m ortality m etastatic lesions involving the p ancreatic head , tu mors of
rates of less than 5%, w ith an associated com plication rate of the d istal bile d u ct, am p u lla, and d u od enu m, as w ell as for
10% to 25% (29–31). Long-term mortality has been rep orted chronic pancreatitis w ith sym ptom atic d isease involving
to be m u ch higher, in som e series as high as 50% at 5 years p rim arily the p ancreatic head . The p roced u re is rarely per-
(31). Continu ed alcoholism has been an im p ortant conform ed for m assive inju ry of the head of the p ancreas
tribu ting factor to this high rate of m ortality. involving the d u od enu m , d istal com m on bile d u ct, or por-
tal vein. As p erform ed tod ay, p ancreaticod u od enectom y
Recurrent/Persistent Pain. Majority of p atients rem ain p ain- involves the rem oval of the p ancreatic head , the d uod e-
free or have significantly im proved pain follow ing the op- nu m , the gallblad d er, and the d istal com m on bile d uct,
erative p roced u re. Recurrent or p ersistent pain follow ing a w ith or w ithou t the rem oval of the gastric antru m . Recon-
lateral p ancreaticojeju nostom y w arrants investigation to stru ction after p ancreaticod u od enectom y requ ires anasto-
ru le ou t other p otential sou rces of p ain, inclu d ing p ep tic m osis of the p roxim al jeju nu m to the p ancreatic rem nant,
ulcer d isease and biliary strictu re. If other d isease processes bile d u ct, and gastrojeju nostom y (or d u od enojeju nostom y
are exclu d ed , an ERCP or m agnetic resonance cholan- if a pylorus-preserving technique is u sed ).
giop ancreatograp hy (MRCP) shou ld be p erform ed to ex-
am ine the p atency of the p ancreaticojeju nal anastom osis ■ Complications
and to ensu re that there are no u nd rained segm ents of the Mortality
pancreatic d u ct. If the anastomosis is occlud ed or if resid u al
und rained segm ents are id entified , red rainage can p rovid e Since the ad vent of pancreaticod u od enectom y (Whip ple
satisfactory p ain relief (32). p roced u re) to treat ad enocarcinom a of the p ancreatic
head , ou tcomes follow ing p ancreaticod u od enectomy have
Endocrine and Exocrine Insufficiency. An im m ed iate change im p roved su bstantially. Previou sly, op erative m ortality
in insu lin requ irem ent is u ncom m on after p ancreaticoje- rates as high as 20% w ere not u ncom m on. In recent tim es,
junostomy as resection of pancreatic tissue is not performed . better resu lts have been rep orted , w ith op erative m ortality
In one series of p atients, follow ed for 10 years after p ancre- rates w ell below 5% at m any large acad em ic centers. One
aticojeju nostom y, ap proxim ately 20% experienced w orsen- case series of 650 consecu tive p atients u nd ergoing pancre-
ing of d iabetes, a likely result of continu ed gland (and islet) aticod u od enectom y d escribed a m ortality rate of 1.7% (35),
d estruction w ith time d ue to the initial insult inciting the in- and other stu d ies w ith m ore than 100 p atients have
flam m atory p rocess (33). While d u ctal d rainage d oes not rep orted no p ostop erative d eaths (36,37). The reasons for
im p rove established p ancreatic end ocrine or exocrine in- the d ecline in operative m ortality rates are likely m ultifac-
sufficiency, som e d ata suggest that the p rogression of p an- torial, inclu d ing refinem ents in op erative techniqu es as
creatic d ysfunction may be slow ed in patients w ho und ergo w ell as im p rovements in p eriop erative care. H ow ever,
a d rainage p roced u re. A stu d y by N ealon and Thom p son large p op u lation-based stu d ies still d em onstrate that m or-
used a 5-p oint grad ing system to m easu re severity of p an- tality rates rem ain high at m any sm aller hosp itals. In fact,
creatitis (ERCP find ings, oral glucose testing, and three d if- of all p roced u res analyzed in a large stu d y exam ining vol-
ferent m easu res of exocrine fu nction). In patients w ith m ild u m e-related d ifferences in m ortality for 14 d ifferent proce-
to m od erate chronic p ancreatitis w ho u nd erw ent d u ctal d e- d u res, the greatest volu m e-related d ifferences in m ortality
com p ression, only 13% p rogressed to severe chronic p an- w ere observed w ith p ancreatic resection, w ith ad justed
creatitis, as op p osed to a control grou p in w hom 78% m ortality rates at very low volu m e hosp itals ( 1 case/
progressed to severe d isease (34). year) of 16.3% versu s 3.8% at very high volu m e hospitals
( 16 cases/ year) (Fig. 36.6) (38). While a nu m ber of initia-
Pancreatic Fistula. Postoperative pancreatic fistulas follow - tives are u nd erw ay to better u nd erstand the reasons for
ing lateral p ancreaticojeju nostom y are u ncom m on, p roba- these d ifferences and how this issu e can be ad d ressed from
bly becau se the gland is qu ite firm and easily hold s su tu res. a national healthcare p ersp ective, cu rrent d ata su p port per-
These fistu las u su ally close sp ontaneou sly w ith closed su c- form ance of p ancreaticod u od enectom ies in high volu m e
tion d rainage. centers.
Pancreatic Fistula
■ PANCREATICODUODENECTOMY Pancreatic fistu las, u su ally resu lting from an anastom otic
leak follow ing p ancreaticojeju nostom y, are an im portant
■ Introduction cau se of m orbid ity and m ortality follow ing p ancreatico-
Pancreaticod u od enectom y, as d escribed by Whip p le in d u od enectom y. In the setting of p ancreaticod uod enal
1935, is the stand ard surgical treatm ent for pancreatic ad e- resection, a p ancreatic fistu la is generally d efined as the
nocarcinom a. This operation is also p erform ed for other p ersistent d rainage of 50 m l or m ore p er d ay of am ylase-
pancreatic neop lasm s su ch as cystic neop lasm s, intrad u ctal rich flu id on or after p ostop erative d ays 3 throu gh 10 (39).
FIGURE 36.6. Adjusted in-hospital or 30-day mortality among Medicare patients (1994 through 1999), according to quintile of total hos-
pitalization volume for resections of gastrointestinal cancer. (From Birkmeyer J D, Stukel TA, Siewers AE, et al. Surgeon volume and oper-
ative mortality in the United States. N Engl J Med 2003;349(22):2117–2127, with permission.)
A m ore liberal d efinition of p ancreatic fistu la w as recently anastom osis (n 46) to an end -to-sid e (d u ct-to-m u cosa,
prop osed by the International Stu d y Grou p on Pancreatic u sing a stent) anastom osis (n 47) (46). The end -to-end ,
Fistu la (ISGPF): the presence of am ylase-rich flu id (greater invaginating techniqu e w as associated w ith a trend tow ard
than three tim es the u p p er lim it of norm al in seru m ) of a a higher fistu la rate com p ared to the end -to-sid e techniqu e
measu rable volu m e on or after postop erative d ay 3 (40). u tilizing stents (15% vs. 4%, p 0.09). N o d ifferences
The incid ence of p ancreatic anastom otic leak varies from in overall p ostop erative m orbid ity or m ortality w ere
5% to 25% in m ost series (41–43). An increased rate of fis- observed betw een the tw o grou p s. The u se of pancreatic
tu la form ation has been associated w ith p ancreatic gland s stents to d ecrease fistu la rate rem ains controversial. A
w ith a soft consistency. Becau se pancreatic fistu la form a- large, rand om ized p rosp ective trial at Johns H opkins
tion has been id entified as su ch a com m on p roblem after d em onstrated that internal p ancreatic d u ct stenting d id not
pancreaticod u od enectom y, variations in techniqu es for alter the rate of fistu la formation follow ing pancreatico-
managing the pancreatic rem nant as w ell as the u tility of d u od enectom y, even in p atients w ith a soft/ norm al pan-
treatm ent w ith p eriop erative octreotid e have been stu d ied . creatic rem nant (47). H ow ever, a second , large rand om ized
In an effort to d ecrease the p ancreatic fistu la rate follow - trial in H ong Kong com paring the efficacy of external pan-
ing p ancreaticod u od enectom y, a variety of technical m od i- creatic stenting to no stent after p ancreaticod u od enectom y
fications in hand ling of the pancreatic remnant have been show ed that the stented group had a significantly low er
evalu ated . A m eta-analysis of the published literatu re from p ancreatic fistu la rate than the nonstented grou p (6.7% vs.
1965 to 1980 revealed that p ancreatic fistula form ation w as 20%, p 0.032) (48). Possible reasons for the d iscrepancies
statistically m ore frequ ent after sim p le su tu re ligation of noted in the tw o stu d ies inclu d e the follow ing: the u se of
the p ancreatic rem nant than after p ancreaticojeju nostom y the invagination technique in som e patients in the H opkins
(44). This w as corroborated by a m ore recently p u blished stu d y m ight have red u ced the p otential benefit of stenting,
trial by Tran et al., rand om izing p atients u nd ergoing p an- a long external stent m ight have d ecreased the likelihood of
creaticod u od enectom y for p eriam p u llary or p ancreatic stent m igration, and an external stent m ay have better
ad enocarcinom a to p ancreaticojeju nostom y (n 83) or allow ed d iversion of activated p ancreatic ju ice from the
obliteration of the p ancreatic d u ct w ithou t anastom osis anastom osis.
(n 86) (45). Occlu sion of the p ancreatic d u ct resu lted in Another op tion for d rainage of the p ancreatic rem nant
significantly higher rates of p ancreatic fistu la (17% vs. 5%) is p ancreaticogastrostom y. The u se of this techniqu e w as
and p ancreatic end ocrine insu fficiency. Other stu d ies initially based on several retrosp ective series rep orting
have exam ined the effects of d ifferent m ethod s of p ancre- low er fistula rates w ith pancreaticogastrostomy versus pan-
atic-jeju nal reconstruction on pancreatic fistula form ation. creaticojejunostomy. In a prospective trial by Yeo et al. eval-
One p rosp ective stu d y in p atients u nd ergoing p ancreatico- u ating 146 p atients und ergoing pancreaticod u od enectomy,
d u od enectom y for periam pullary tum ors com pared tw o p atien ts w ere ran d om ized intraop eratively to either p an-
m ethod s of reconstru ction: an end -to-end , invaginating creaticogastrostom y (n 73) or p an creaticojeju nostom y
(n 72) (49). Pancreaticojeju nostom y w as perform ed in lished p ancreatic anastom otic leaks that requ ire percu ta-
tw o layers w ithou t stents in either an end -to-sid e or end -to- neous d rainage.
end fashion at the su rgeon’s d iscretion. Pancreaticogastros-
tom y w as p erform ed by anastom osing the p ancreatic Anastomotic Leak at Biliary-Enteric Anastomosis
rem nant to the p osterior gastric w all. The incid ence of p an- Developm ent of an anastom otic leak at the biliary-enteric
creatic fistu la w as 11% for pancreaticojejunostom y and 12% anastom osis is rep orted to occu r in 1% to 8% of p ancreati-
for pancreaticogastrostom y reconstructions. This trial cod u od enectomies from several large series (41–43,57).
d em onstrated that pancreaticogastrostom y is a safe and Diagnosis of a biliary leak m ay be evid ent if an intraopera-
viable op tion for p ancreatic-enteric reconstru ction w ith tively p laced d rain d evelop s biliou s ou tp u t, or m ay require
sim ilar p eriop erative m orbid ity and m ortality. evalu ation w ith a cholangiogram or fistu logram . A sm all
The effectiveness of p erioperative octreotid e in p atients bile leak that is ad equ ately d rained often seals sponta-
und ergoing elective pancreatic resection w as initially neou sly. In m ore p ersistent cases, biliary anastom otic leaks
investigated in several prospective, rand omized Europ ean m ay requ ire a transhep atic catheter to allow for external
trials (50–53). A su bsequent m eta-analysis of the Europ ean biliary d rainage.
trials fou nd that the u se of octreotid e significantly red u ced
Delayed Gastric Emptying
the rate of p ancreatic fistula form ation (10.7% for octreotid e
vs. 23.4% for p lacebo) (54). H ow ever, there w ere inherent Delayed gastric em ptying is a frequent and significant p ost-
lim itations in extrapolating the d ata from these stu d ies to operative problem follow ing pancreaticod u od enectomy. In
valid ate the u se of p rop hylactic octreotid e in p atients most series, d elayed gastric emptying, w hich is d efined as
und ergoing p ancreaticod u od enectom y. First, the trials the need for postoperative nasogastric d ecom pression for
exam ined all types of pancreatic resections includ ing pan- more than 10 d ays, has a rep orted incid ence ranging from
creaticod u od enectom y, d istal pancreatectom y, and enu cle- 20% to 40% (58,59). Althou gh not life-threatening, d elayed
ation. It is p ossible that the fistu la rates vary based on the gastric emp tying results in a significant prolongation of
type of resection, and therefore, this result m ay not be hosp ital stay and contribu tes to increased hosp italization
applicable for p ancreaticod u od enectom y. Second , the rates costs. The etiology of d elayed gastric em p tying follow ing
of p ancreatic fistu la rep orted in these stu d ies w ere m u ch p ancreaticod u od enectom y is u ncertain; p ossible etiologies
higher than rates reported at m ajor institutions in the inclu d e d ecreased m otilin levels, rem oval of the d uod enal
United States, w hich m ight am plify the benefit of p acem aker and d isru p tion of gastrod u od enal neu ral con-
octreotid e observed in these stud ies (55). To ad d ress these nections. Erythrom ycin, a m otilin agonist, has been found
issues, Low y et al. (56) evaluated the use of perioperative to im prove gastric em ptying of both solid s and liqu id s
octreotid e sp ecifically in p atients u nd ergoing p ancreatico- w hen ad m inistered intravenou sly d u ring the p ostop era-
d u od enectom y for m alignant d isease. N o significant d iffer- tive p eriod . To test the p otential role of erythrom ycin in
ences w ere fou nd in pancreatic fistu la rates, m ortality, or gastric em p tying follow ing p ancreaticod u od enectom y, a
length of hosp italization betw een the tw o grou ps. In a sim - p rosp ective, rand om ized trial w as p erform ed in w hich
ilar stu d y on p ancreatic cancer patients by Yeo et al., no d if- p atients received either 200 m g of intravenou s erythrom y-
ferences w ere fou nd in p ancreatic fistu la rate in patients cin or p lacebo from the third to tenth p ostop erative d ays,
treated w ith octreotid e versus placebo (39). Mu ltivariate and on the tenth p ostop erative d ay, d u al p hase gastric
analysis revealed that soft p ancreatic gland consistency em p tying stu d ies w ere p erform ed (58). The erythrom ycin
w as an ind ep end ent p red ictor of the d evelop m ent of a p an- grou p had a significantly red u ced incid ence of d elayed
creatic fistu la. Overall, these stu d ies d em onstrate that rou - gastric em p tying (19% vs. 30%), w ith m easu rable im prove-
tine u se of p eriop erative octreotid e for p atients u nd ergoing m ents in gastric em p tying stu d ies, su p p orting the use of
p ancreaticod u od enectom y cannot be ju stified based on the erythrom ycin to d ecrease early d elayed gastric em ptying
available d ata. Fu rther stu d ies are need ed to d eterm ine if after p ancreaticod u od enectom y.
p eriop erative octreotid e is of benefit in sp ecific p atient
grou p s w ho u nd ergo p ancreaticod u od enectom y, i.e., soft ■ Other factors influencing morbidity and mortality
versu s firm gland s, or in p atients w ith m alignant versu s following pancreaticoduodenectomy
benign d isease. The u se of fibrin glu e has not been fou nd
to p rovid e any benefit in d ecreasing p ancreatic fistu la Hyperbilirubinemia and Preoperative Biliary Drainage
form ation. The effect of p reop erative hyp erbiliru binem ia on m ortality
Pancreatic fistulae that d evelop follow ing pancreatico- risk w ith p ancreaticod u od enectom y rem ains controversial.
d u od enectom y can u sually be m anaged conservatively if While qu ite a few stu d ies exam ining variou s other su rgical
there is no evid ence of abd om inal sepsis. The p resence of a p roced u res have show n that p reop erative jau nd ice is
pancreatic fistu la shou ld be suspected in a postop erative associated w ith increased m ortality risk, the literatu re
patient w ho d evelop s clinical evid ence of intra-abd om inal d escribing the effect of p reop erative hyp erbiliru binem ia on
sepsis. Isolated flu id collections shou ld be d rained , p ercu - m ortality follow ing p ancreaticod u od enectomy is u nclear.
taneou sly if p ossible, and usually heal spontaneou sly if While several stud ies have not reported an effect of preoper-
ad equ ately d rained . Octreotid e is often used to treat estab- ative hyperbilirubinemia on perioperative mortality (60–63),
other stu d ies have id entified hyp erbiliru binem ia as a p ancreaticod u od enectom y versu s PPPD. The PPPD group
risk factor for m ortality after p ancreaticod u od enectom y had a significantly shorter operative tim e and red u ced
(64–67). In a retrospective analysis of 279 p atients by blood loss. The incid ence of d elayed gastric em p tying w as
Braasch et al., patients w ith serum bilirubin 20 mg/ 100 ml id entical in both grou p s. A sim ilar incid ence of d elayed
had significant higher m ortality rates (6/ 28, 22%) than gastric em ptying w ith stand ard versu s PPPD has been ver-
patients w ith low er bilirubin levels (29/ 251, 11.5%), su g- ified in other stu d ies (76,77). Postop erative nutritional
gesting that the m ortality rate m ay w ell be associated w ith p aram eters rem ain norm al in m ost p atients regard less of
the severity of hyp erbiliru binem ia. w hich p roced u re is p erform ed . There w ere no d ifferences
While there d oes rem ain som e controversy as to in tu m or recu rrence or long-term su rvival (59,74). The pub-
w hether p reop erative hyp erbiliru binem ia contribu tes to lished d ata d o not ind icate a significant ad vantage of the
mortality, it is not clear w hether risk can be d ecreased by PPPD over stand ard p ancreaticod u od enectom y, and the
preop erative biliary d rainage. Results from a nu m ber of p roced u re chosen can be at the su rgeon’s d iscretion.
prosp ective trials and retrospective analyses have not
show n a red u ction in op erative m ortality by p reop erative
biliary d rainage (67–71). A nu m ber of stu d ies have sou ght
■ COMPLICATIONS OF DISTAL
to ad d ress the issu e of w hether p reop erative biliary AND SUBTOTAL PANCREATECTOMY
d rainage im p acts ou tcom es follow ing p ancreaticod u o- ■ Introduction
d enectom y. Patients w ho had p reop erative biliary stents
placed clearly exp erienced significantly increased rates of Distal p ancreatectom y (50%–60% of the gland ) is per-
w ou nd infection (increased from average of 4% to 10%), form ed for a variety of benign and m alignant cond itions.
w ith m ixed resu lts regard ing the effect of p reop erative They inclu d e chronic p ancreatitis, cystic neop lasm s, intra-
stenting on p ancreatic fistula form ation. N o d ifferences d u ctal p ap illary m u cinou s tu m ors, p ancreatic ad enocarci-
w ere observed betw een stented and u nstented grou p s in nom a, neu roend ocrine tu mors, p ancreatic pseu d ocysts,
incid ence of intra-abd om inal abscess or other m ajor com - and resection en bloc for m anagem ent of tu m ors arising
plications. Overall, the prepond erance of d ata d oes not su g- from nearby organs su ch as the stom ach or kid ney. Subtotal
gest benefit or d etriment for preoperative biliary d rainage p ancreatectom y (80%–95% of the gland ) m ay be required
proced ures w ith regard to periop erative mortality. Preoper- for neop lastic d isease p rocesses requ iring a m ore extensive
ative biliary d rainage d emonstrates an increased risk of resection. Althou gh com m only p erform ed in the past,
w ound infection and may increase the risk of pancreatic fis- subtotal resection of the pancreas is rarely ind icated for the
tula form ation. In general, preoperative biliary d rainage is treatm ent of intractable p ain cau sed by d iffu se chronic
relatively safe but should be reserved for patients w ith p ancreatitis w hen the p ancreatic d u ct is not d ilated . In both
intolerable jau nd ice in w hich d efinitive su rgical treatm ent is d istal and su btotal p ancreatectom y, the sp leen is typically
d elayed . removed becau se of the extensive collaterals that exist
betw een the splenic vessels and the bod y and tail of the
Surgical Technique: Pylorus-Preserving p ancreas. If transection of the p ancreas is carried out to the
Pancreaticoduodenectomy Versus left of the p ortal and su p erior m esenteric vessels, this con-
Standard Pancreaticoduodenectomy stitu tes a less than 60% resection, w hereas resection at the
In the classic p ancreaticod uod enectom y, as d escribed by level of the p ortal vein and su p erior m esenteric vessels is a
Whip p le (72), an antrectom y is perform ed , w hereas in the 60% to 70% resection, and resection to the right of the ves-
pyloru s-p reserving m od ification, the d uod enum is tran- sels is an 80% or greater resection (Fig. 36.7). In a large,
sected 2 to 3 cm d istal to the p ylorus. The rationale for the m u lticenter rep ort in w hich lap aroscop ic d istal p ancreatec-
more extensive gastric resection in the stand ard Whipple tom y w as com pared to open d istal pancreatectom y in a
proced u re w as that it w as a better oncologic operation, and m atched cohort of p atients, lap aroscop ic d istal pancreatec-
it w ou ld red u ce the acid burd en and subsequ ent incid ence tom y w as associated w ith less m orbid ity and a shorter hos-
of m arginal u lceration. Pyloru s preservation, on the other p ital stay than op en d istal p ancreatectom y. Consequently,
hand , has been tou ted as maintaining m ore norm al gas- it shou ld be consid ered in ap p rop riate p atients (78). Cu r-
trointestinal p hysiology, specifically in term s of acid p ro- rently, the ind ications for lap aroscop ic d istal pancreatec-
d u ction, gastric reservoir and em ptying fu nctions, and tom y and the learning curve for com petency are being
horm one secretion. d efined .
A num ber of stud ies have been p erform ed to com pare
the ou tcom es of the stand ard versu s p yloru s-p reserving ■ Complications
proced u re. Several reports have show n no d ifference in
su rvival betw een p atients w ith p eriam p u llary tu m ors Pancreatic Fistula Formation
treated w ith p yloru s-p reserving p ancreaticod u od enec- The pancreatic fistu la rate in patients und ergoing d istal
tom y (PPPD) versu s stand ard p ancreaticod u od enectom y p ancreatectom y is rep orted to be 5% to 25% (41,79–81). Su r-
(73–75). In one of the reports (73), a rand om ized clinical geons have tried to d eterm ine the op tim al m anagem ent
trial of 77 p atients com pared the clinical results of classic strategy for the resid u al transected p ancreatic parenchym a
FIGURE 36.7. Level of parenchymal transec-

tion for 50%, 60%–70%, and 85% distal pancre-
atectomy.
50% resection
60%–70% resection
'0
4
h er
isc
HRF
85% resection
and the d ivid ed p ancreatic d u ct. Com m only used tech- stu m p closu re. There are no stu d ies cu rrently that have
niqu es for m anagem ent of the transected parenchym a ad equ ately ad d ressed the role for rou tine u se of octreotid e
includ e oversew ing of the rem nant or staple closure, w ith after elective d istal p ancreatectom y.
or w ithou t d irect d u ctal ligation. In tw o large series, there
w ere no d ifferences in p ancreatic leak rates betw een Endocrine Insufficiency
patients w hose stu m ps w ere sutured versu s those w hose Diabetes m ay be a com p lication of d istal pancreatectom y
stum p s w ere stap led (79,81). H ow ever, in a stu d y by Bil- or su btotal p ancreatectom y in p atients op erated u pon for
im oria et al., the incid ence of pancreatic leak w as fou nd to chronic p ancreatitis if a m ajor p ortion of the gland is
be significantly d ecreased (9.6% versus 34%, p 0.001) removed . In an otherw ise norm al p ancreas, as m u ch as 80%
w hen the p ancreatic d u ct w as id entified and ligated , ind e- of the p ancreas m ay be rem oved w ithou t the d evelopm ent
pend ent of w hether the rem nant w as su tu red or stap led of d iabetes. H ow ever, in the setting of d iffu se p arenchym al
closed . Based on these d ata, every effort shou ld be m ad e to d isease, as in chronic p ancreatitis, resection of as little as
d irectly ligate the pancreatic d u ct follow ing parenchym al 50% of the gland m ay cau se d iabetes or m ay w orsen d ia-
transection, irresp ective of the techniqu e em ployed for betes in chronic p ancreatitis patients w ho have anteced ent
d iabetes before surgical resection. In several large series, the absence of the m ajor glu coregu latory horm ones insu lin
overall reported incid ence of new onset, insulin-d epend ent and glu cagon, (b) instability, and (c) frequ ent hypo-
diabetes mellitus follow ing distal pancreatectomy is approx- glycem ia, w ith the latter p aram eters im p roving w ith rigor-
imately 8% (80,81). How ever, in patients with chronic pan- ou s hom e glu cose m onitoring. Dresler et al. (88) reported
creatitis, the risk is reported to range from 12% to 46% on the m etabolic consequ ences of total p ancreatectom y in
(82–85). 49 p atients, w ith one-third of the p atients being follow ed
for m ore than 48 m onths. Althou gh p atients becam e d ia-
Exocrine Insufficiency betic and exp erienced alterations in lifestyle, m ost patients
Like d iabetes, exocrine insufficiency following d istal or w ere able to resu m e a reasonable fu nctional statu s and
subtotal pancreatectomy is pred ominantly a complication level of activity. Only one of the 49 p atients d ied from m eta-
that occurs in patients w ith chronic pancreatitis. Exocrine bolic com p lications d u e to the su rgical p roced ure, w hile no
insufficiency occurs in about one-third of patients with a other p atients had seriou s sequ elae from their d iabetes. At
diagnosis of chronic pancreatitis before surgical intervention the tim e of the rep ort, no p atient had d evelop ed clinically
and has been reported to be present in 55% of postsurgical overt d iabetic m icro- or m acrovascu lar d isease. Other
patients (83). Exocrine insufficiency is not consid ered a seri- rep orts have d em onstrated good p erform ance statu s in
ous complication of pancreatic surgery and can usually be p atients follow ing total p ancreatectom y, w ith interm ittent
easily treated by oral pancreatic enzyme supplementation. hyp oglycemia being the m ost frequ ent com p lication (89).
The u se of d ifferent insu lin form u lations w ith varying half-
lives as w ell as the d evelopm ent of an effective su bcu ta-
■ COMPLICATIONS OF TOTALPANCREATECTOMY
neous insulin infusion pu m p has im proved postop erative
■ Introduction glu cose control (90). For p atients w ith severe, u nrem itting
p ain d u e to chronic p ancreatitis, an alternative approach is
Total p an createctom y has been u sed to treat both ben ign total p ancreatectom y w ith either au tologou s islet cell trans-
an d m alignan t d isease of the p ancreas, bu t its u se h as p lantation or transp lantation of a p ancreatic allograft. In
been lim ited by concerns abou t m anagem ent of the ap an- highly sp ecialized centers, this ap p roach has d em onstrated
creatic state w ith its attend ant total end ocrine and p rom ising resu lts (91,92).
exocrine insu fficiency. Total p ancreatectom y is a viable
op tion for the treatm ent of p atients w ith chronic p ancre-
atitis com p licated by d iffu se gland in volvem en t and ■ REFERENCES
severe, u nrem itting p ain, m u lticentric or extensive neu - 1. Yeo CJ, Bastid as JA, Lynch-N yhan A, et al. The natu ral history of p an-
roend ocrine tu m ors, p atients w ith fam ilial p ancreatic creatic p seu d ocysts d ocu m ented by com p u ted tom ograp hy. Surg
cancer w ith p rem alignant lesions, and in p atients w ith Gynecol Obstet 1990;170:411–417.
2. Vitas GJ, Sarr MG. Selected m anagem ent of p ancreatic p seu d ocysts:
intrad u ctal p ap illary m u cinou s neop lasia w ith d iffu se op erative versus expectant m anagem ent. Surgery 1992;111:123–130.
m ain d u ct involvem ent or invasive d isease. Total p an cre- 3. Tanaka M, Chari S, Ad say V, et al. International consensu s gu id elines
atectom y w as a p op u lar op eration for ad enocarcinom a of for m anagem ent of intrad uctal papillary m ucinous neoplasm s and
m u cinou s cystic neop lasm s of the p ancreas. Pancreatology 2006;6:17–32.
the p ancreas in the 1970s becau se the long-term su rvival 4. Johnson LB, Rattner DW, Warshaw AL. The effect of size of giant p an-
follow in g p an creaticod u od en ectom y w as relatively p oor. creatic pseu d ocysts on the outcom e of internal d rainage proced ures.
H ow ever, the resu lts from total p an createctom y in this Surg Gynecol Obstet 1991;173:171–174.
5. Siperstein A. Laparoend oscop ic ap p roach to p ancreatic p seu d ocysts.
grou p of p atients w ere not im p roved (86), and there is Semin Laparosc Surg 2001;8:218–222.
cu rrently little d ata to su p p ort the rou tine u se of total 6. Mori T, Abe N , Su giyam a M. Lap aroscop ic p ancreatic cystogastros-
p an createctom y in this setting. tom y. J Hepatobiliary Pancreat Surg 2002;9:548–554.
7. Bhattacharya D, Am m ori BJ. Minim ally invasive ap p roaches to m an-
agem ent of p ancreatic p seu d ocyst: review of the literatu re. Surg
Laparosc Endosc Percutan Tech 2003;13:141–148.
■ Complications 8. von Sonnenberg E, Wittich G, Casola G. Percu taneou s d rainage of
infected and noninfected p ancreatic p seu d ocysts: exp erience in 101
Mortality cases. Radiology 1989;170:757–761.
The m ortality rate for total p ancreatectom y has d em on- 9. Ad am s D, And erson M. Percu taneou s catheter d rainage com p ared
w ith internal d rainage in the m anagem ent of p ancreatic pseu d ocysts.
strated the sam e im p rovem ent over tim e as that observed Ann Surg 1992;215:571–578.
w ith p ancreaticod u od enectom y. While it w as not u ncom - 10. D’Egid io A, Schein M. Percu taneou s d rainage of p ancreatic p seu d o-
mon for m ortality rates follow ing total pancreatectom y to cysts: a p rosp ective stu d y. World J Surg 1991;16:141–146.
11. Criad o E, DeStefano AA, Weiner TM, et al. Long term resu lt of p ercu ta-
be as high as 26% to 28% in old er series, reports from sev- neou s catheter d rainage of p ancreatic p seu d ocysts. Surg Gynecol Obstet
eral series over the last d ecad e list operative m ortality rates 1992;175:293–298.
ranging from 3% to 5% (86,87). 12. Spivak H , Gallow ay JR, Am erson JR, et al. Managem ent of p ancreatic
pseu d ocysts. J Am Coll Surg 1998;186:507–511.
13. H eid er R, Meyer AA, Galanko JA, et al. Percu taneou s d rainage of p an-
Endocrine Insufficiency creatic pseu d ocysts is associated w ith a higher failu re rate than su rgical
The m ost significant com p lication encou ntered in p atients treatm ent in unselected p atients. Ann Surg 1999;229:781.
14. N ealon WH , Walser E. Main p ancreatic d u ctal anatom y can d irect
w ho u nd ergo total p ancreatectom y is end ocrine insu ffi- choice of m od ality for treating pancreatic pseu d ocysts (surgery versu s
ciency. Pancreatogenic d iabetes is characterized by (a) percu taneou s d rainage). Ann Surg 2002;235:751–758.
15. De Palm a GD, Galloro G, Pu zziello A, et al. End oscop ic d rainage of 43. Sohn TA, Yeo CJ, Cam eron JL. Resected ad enocarcinom a of the p an-
p ancreatic p seu d ocysts: a long-term follow -u p stu d y of 49 p atients. creas- 616 p atients: resu lts, ou tcom es, and p rognostic ind icators. J Gas-
Hepatogastroenterology 2002;49:1113–1115. trointest Surg 2000;4:567–579.
16. Binm oeller KF, Seifert H , Walter A, et al. Transp ap illary and transm u ral 44. Bartoli FG, Arnone GB, Ravera G, et al. Pancreatic fistu la and relative
d rainage of p ancreatic p seu d ocysts. Gastrointest Endosc 1995;42:219. m ortality in m alignant disease after pancreaticoduod enectom y. Review
17. Lillem oe K, Yeo CJ. Managem ent of com p lications of p ancreatitis. Curr and statistical m eta-analysis regard ing 15 years of literatu re. Anticancer
Prob Surg 1998;35:33–51. Res 1991;11:1831–1848.
18. Carr JA, Cho JS, Shepard AD, et al. Visceral p seu d oaneu rysm s d ue to 45. Tran K, van Eijck C, Di Carlo V, et al. Occlu sion of the p ancreatic d u ct
p ancreatic p seud ocysts: rare bu t lethal com p lications of p ancreatitis. versus pancreaticod uod enectom y: a p rosp ective rand om ized trial. Ann
J Vasc Surg 2000;32:722–730. Surg 2002;236:422–428.
19. Steckm an ML, Dooley MC, Jaqu es PF, et al. Major gastrointestinal hem - 46. Chou FF, Sheen-Chen SM, Chen YS, et al. Postop erative m orbid ity and
orrhage from peripancreatic blood vessels in pancreatitis: treatm ent by m ortality of pancreaticod u od enectom y for p eriam p u llary cancer. Eur J
em bolotherapy. Dig Dis Sci 1984;29:486–497. Surg 1996;162:477–481.
20. Bresler L, Boissel P, Grosd id ier J. Major hem orrhage from p ancreatic 47. Winter JM, Cam eron JL, Cam p bell KA, et al. Does p ancreatic d u ct
p seu d ocysts and p seu d oaneu rysm s cau sed by chronic p ancreatitis: stenting d ecrease the rate of p ancreatic fistu la follow ing p ancreatico-
su rgical therap y. World J Surg 1991;15:649–653. d u od enectom y? Resu lts of a p rosp ective rand om ized trial. J Gastroin-
21. Brad ley EL, Allen K. A p rosp ective longitu d inal stu d y of observation test Surg 2006;10:1280–1290.
versu s su rgical intervention in the m anagem ent of necrotizing p ancre- 48. Poon RTP, Fan ST, Lo CM, et al. External d rainage of p ancreatic d u ct
atitis. Am J Surg 1991;161:19–25. w ith stent to red uce leakage rate of pancreatectom y after pancreatico-
22. Bu chler MW, Gloor B, Mu ller CA, et al. Acu te necrotizing p ancreatitis: d uod enectom y: a prospective rand om ized trial. Ann Surg 2007;246:
treatm ent strategy accord ing to statu s of infection. Ann Surg 2000;232: 425–435.
619–626. 49. Yeo CJ, Cam eron JL, Maher MM, et al. A p rosp ective rand om ized trial
23. Warshaw AL. Pancreatic necrosis: to d ebrid e or not to d ebrid e—that is of pancreatico-gastrostom y and p ancreatico-jeju nostom y after p ancre-
the qu estion. Ann Surg 2000;232:627–629. aticod u od enectom y. Ann Surg 1995;225:580–588.
24. Branu m G, Gallow ay J, H irchow itz W, et al. Pancreatic necrosis: resu lts 50. Bu chler M, Friess H , Klem p a I, et al. Role of octreotid e in the p reven-
of necrosectom y, p acking, and u ltim ate closu re over d rains. Ann Surg tion of p ostop erative com p lications follow ing p ancreatic resection. Am
1998;227:870–877. J Surg 1992;163:125–130.
25. Fernand ez-d el Castillo C, Rattner DW, Makary MA, et al. Debrid em ent 51. Ped erzoli P, Bassi C, Falconi M, et al. Efficacy of octreotid e in the p re-
and closed packing for the treatm ent of necrotizing p ancreatitis. Ann vention of com p lications follow ing p ancreatic resection: Italian Stu d y
Surg 1998;228:676–684. Grou p. Br J Surg 1994;81:265–269.
26. Tsiotos GG, Lu que-d e Leon E, Soreid e JA, et al. Managem ent of necro- 52. Montorsi M, Zago M, Mosca F, et al. Efficacy of octreotid e in the p reven-
tizing p ancreatitis by rep eated op erative necrosectom y u sing a zip p er tion of pancreatic fistula after elective pancreatic resections: a prospec-
techniqu e. Am J Surg 1998;175:91–98. tive, controlled , rand om ized clinical trial. Surgery 1995;117:26–31.
27. Broom e AH , Eisen GM, H arland RC, et al. Qu ality of life after treat- 53. Friess H, Beger HG, Sulkowski U, et al. Randomized controlled m ulti-
m ent for p ancreatitis. Ann Surg 1996;223:665–672. centre study of the prevention of complications by octreotide in patients
28. Tsiotos GG, Sm ith CD, Sarr MG. Incid ence and m anagem ent of p ancre- undergoing surgery for chronic pancreatitis. Br J Surg 1995;82:1270–1273.
atic and enteric fistulas after su rgical m anagem ent of severe necrotiz- 54. Rosenberg L, MacN eil P, Tu rcotte L. Econom ic evalu ation of the u se of
ing pancreatitis. Arch Surg 1995;130:48–52. octreotid e for p revention of com p lications follow ing p ancreatic resec-
29. Brad ley EL. Long-term resu lts of p ancreaticojeju nostom y in patients tion. J Gastrointest Surg 1999;3:225–232.
w ith chronic pancreatitis. Am J Surg 1987;153:207–213. 55. Yeo CJ. Does p rop hylactic octreotid e benefit p atients u nd ergoing elec-
30. Ihse I, Borch K, Larsson J. Chronic p ancreatitis: resu lts of op eration for tive pancreatic resection? J Gastrointest Surg 1999;3:223–224.
relief of pain. World J Surg 1990;14:53–58. 56. Low y AM, Lee JE, Pisters PWT, et al. Prosp ective rand om ized trial of
31. Prinz RA, Greelee H B. Pancreatic d u ct d rainage in 100 p atients w ith octreotid e to prevent p ancreatic fistu la after p ancreaticod u od enectom y
chronic pancreatitis. Ann Surg 1981;194:313–320. for m alignant d isease. Ann Surg 1997;226:632–641.
32. Prinz RA, Aranha GV, Greenlee H B. Red rainage of the p ancreatic d u ct 57. Mied em a BW, Sarr MG, Van H eerd en JA, et al. Com p lications follow -
in chronic p ancreatitis. Am J Surg 1986;151:150–156. ing p ancreaticod u od enectom y. Cu rrent m anagem ent. Arch Surg 1992;
33. Taylor RH , Bagley FH , Braasch JW, et al. Du ctal d rainage or resection 127:945–949.
for chronic p ancreatitis. Am J Surg 1981;141:28. 58. Yeo CJ, Barry MK, Sau ter PK, et al. Erythrom ycin accelerates gastric
34. N ealon WH , Thom p son JC. Progressive loss of p ancreatic fu nction in em ptying after p ancreaticod u od enectom y. A p rosp ective rand om ized
chronic p ancreatitis is d elayed by m ain d u ct d ecom p ression: a longitu - p lacebo-controlled trial. Ann Surg 1993;218:229–238.
d inal p rospective analysis of the m od ified Pu estow p roced u re. Ann 59. Sp anknebel K, Conlon K. Ad vances in the su rgical m anagem ent of
Surg 1993;217:458–468. p ancreatic cancer. Cancer J 2001;7:312–323.
35. Yeo CJ, Cam eron JL, Sohn TA, et al. Six hu nd red fifty consecu tive p an- 60. Sohn TA, Yeo CJ, Cam eron JL, et al. Do p reop erative biliary stents
creaticod uod enectom ies in the 1990’s: p athology, com p lications, out- increase p ostpancreaticod u od enectom y com plications? J Gastrointest
com es. Ann Surg 1997;226:248–260. Surg 2000;4:258–268.
36. Tred e M, Schw all G, Saeger H -D. Su rvival after p ancreaticod u od enec- 61. Pisters PW, H u d ec WA, H ess KR, et al. Effect of p reop erative biliary
tom y: 118 consecu tive resections w ithou t a m ortality. Ann Surg 1990; d ecom p ression on p ancreaticod u od enectom y-associated m ortality in
211:447–458. 300 consecu tive p atients. Ann Surg 2001;234:47–55.
37. Cam eron JL, Pitt H A, Yeo CJ, et al. One hu nd red and forty five consec- 62. Bakkevold KE, Kam bestad B. Morbid ity and m ortality after rad ical and
utive pancreaticoduodenectomies w ithout mortality. Ann Surg 1993;217: p alliative p ancreatic cancer su rgery. Risk factors influ encing short-term
430–438. resu lts. Ann Surg 1993;217(4):356–368.
38. Birkm eyer JD, Siew ers AE, Finlayson EV, et al. H osp ital volu m e and 63. H od u l P, Creech S, Picklem an J, et al. The effect of p reop erative biliary
su rgical m ortality in the United States. New Engl J Med 2002;346(15): stenting on p ostoperative com plications after pancreaticod uod enec-
1128–1137. tom y. Am J Surg 2003;186:420–425.
39. Yeo CJ, Cam eron JL, Lillem oe KD, et al. Does p rop hylactic octreotid e 64. Braasch JW, Gray BN . Consid erations that low er p ancreaticod u od enec-
d ecrease the rates of p ancreatic fistu la and other com p lications after tom y m ortality. Am J Surg 1977;133:480–484.
p ancreaticod u od enectom y? Resu lts of a p rosp ective rand om ized 65. And ren-Sand berg A, Ihse I. Factors influ encing su rvival after total p an-
p lacebo-controlled trial. Ann Surg 2000;232:419–429. createctom y in p atients w ith p ancreatic cancer. Ann Surg 1983;198:
40. Bassi C, Dervenis C, Buttu rini G, et al. Post-op erative p ancreatic fistu la: 605–610.
An International Stu d y Grou p (ISGPF) d efinition. Surgery 2005;138: 66. Bottger TC, Junginger T. Factors influ encing m orbid ity and m ortality
8–13. after pancreaticod u od enectom y: critical analysis of 221 resections.
41. Balcom JH , Rattner DW, Warshaw AL, et al. Ten-year exp erience w ith World J Surg 1999;23:164–171.
733 p ancreatic resections. Arch Surg 2001;136:391–398. 67. Povoski SP, Karpeh MS, Conlon KC, et al. Preoperative biliary drainage:
42. Gou m a DJ, van Geenen RCI, van Gu lik TM, et al. Rates of com plica- im pact on intraoperative bile cultu res and infectiou s m orbid ity and
tions and d eath after p ancreaticod uod enectom y: risk factors and the m ortality after p ancreaticod u od enectom y. J Gastrointest Surg 1999;3:
im p act of hospital volum e. Ann Surg 2000;232:786–795. 496–505.
68. Pitt H A, Gom es AS, Lois JF, et al. Does p reop erative p ercu taneous bil- 80. Fahy BN , Frey CF, H o H S, et al. Morbid ity, m ortality, and technical fac-
iary d rainage red u ce op erative risk or increase hosp ital cost? Ann Surg tors of d istal p ancreatectom y. Am J Surg 2002;183:237–241.
1985;201:545–553. 81. Lillem oe KD, Kau sh al S, Cam eron JL, et al. Distal p ancreatectom y:
69. Tred e M, Schw all G. The com p lications of p ancreatectom y. Ann Surg in d ication s an d ou tcom es in 235 p atien ts. Ann Surg 1999;229:
1988;207:39–47. 693–700.
70. H eslin MJ, Brooks AD, H ochw ald SN , et al. A p reop erative biliary stent 82. Cogbill TH , Moore EE, Morris JA, et al. Distal p ancreatectom y for
is associated w ith increased com plications after pancreatod u od enec- trau m a: a m u lticenter exp erience. J Trauma 1991;31:1600–1606.
tom y. Arch Surg 1998;133:149–154. 83. Sohn TA, Cam p bell KA, Pitt H A, et al. Qu ality of life and long-term
71. Ceu terick M, Gelin M, Rickaert F, et al. Pancreaticod u od enal resection su rvival after su rgery for chronic p ancreatitis. J Gastrointest Surg 2000;
for p ancreatic or p eriam p u llary tu m ors- a ten year exp erience. Hepato- 4:355–365.
gastroenterology 1989;36:467–473. 84. H u tchins RR, H art RS, Pacifico M, et al. Long-term resu lts of d istal p an-
72. Whipp le A. Present d ay su rgery of the p ancreas. N Engl J Med 1942;226: createctom y for chronic p ancreatitis in 90 p atients. Ann Surg 2002;236:
515–518. 612–618.
73. Seiler CA, Wagner M, Sad ow ski C, et al. Rand om ized p rospective trial 85. Slezak LA, And erson DK. Pancreatic resection: effects on glu cose
of pyloru s-p reserving vs. classic d u od enop ancreatectom y (Whip p le m etabolism . World J Surg 2001;25:452–460.
proced u re): initial clinical resu lts. J Gastrointest Surg 2000;4:443–452. 86. Karp off H M, Klim stra DS, Brennan MF, et al. Resu lts of total p ancreate-
74. Mosca F, Giulianotti PC, Balestracci T, et al. Long-term su rvival in p an- ctom y for ad enocarcinom a of the p ancreas. Arch Surg 2001;136:44–47.
creatic cancer: pylorus preserving versu s Whip ple p ancreaticod uo- 87. Flem ing WR, William son RC. Role of total p ancreatectom y in the treat-
d enectom y. Surgery 1997;122:553–566. m ent of p atients w ith end -stage chronic p ancreatitis. Br J Surg 1995;82:
75. Patel AG, Toyama MT, Kusske AM, et al. Pylorus-preserving Whipple 1409–1412.
resection for pancreatic cancer: is it any better? Arch Surg 1995;130:838–843. 88. Dresler CM, Fortner JG, McDerm ott K, et al. Metabolic consequ ences of
76. Crist DW, Sitzm ann JV, Cam eron JL. Im p roved hosp ital m orbid ity, (regional) total p ancreatectom y. Ann Surg 1991;214:131–140.
mortality, and survival after the Whipple proced ure. Ann Surg 1987;206: 89. Assan R, Alexand re JH , Tiengo A, et al. Su rvival and rehabilitation after
358–365. total pancreatectom y: a follow -u p of 36 p atients. Diabete Metab 1985;11:
77. van Berge H enegou w en MI, van Gu lik TM, DeWit LT, et al. Delayed 303–309.
gastric em p tying after stand ard p ancreaticod u od enectom y versu s 90. H eid t DG, Bu rant C, Sim eone DM. Total p ancreatectom y: ind ications,
pyloru s-preserving p ancreaticod u od enectom y: an analysis of 200 con- op erative techniqu e, and p ost-op erative sequ elae. J Gastrointest Surg
secu tive p atients. J Am Coll Surg 1997;185:373–379. 2007;11:209–216.
78. Kooby DA, Gillesp ie T, Bentrem D, et al. Left-sid ed p ancreatectom y: a 91. Rilo R, Ahm ad SA, D’Alessio SA, et al. Total p ancreatectom y and au tol-
m u lticenter com parison of lap aroscop ic and op en ap p roaches. Ann ogous islet transplantation a m eans to treat severe chronic pancreatitis.
Surg 2008;248:438–446. J Gastrointest Surg 2003;7:978–989.
79. Bilim oria MM, Corm ier JN , Mu n JE, et al. Pancreatic leak after left p an- 92. Gruessner RW, Sutherland DE, Du nn DL, et al. Transp lant op tions for
createctom y follow ing m ain p ancreatic d u ct ligation. Br J Surg 2003;90: p atients u nd ergoing total p ancreatectom y for chronic p ancreatitis.
190–196. J Am Coll Surg 2004;198:559–567.
CHAPTER
37
Complications of Intestinal
Surgery: Small Bowel
Arden M. Morris
The sm all bow el integrates d igestive and barrier fu nctions quality of life (5). Prevention of bow el ed ema d ue to exces-
resulting in a m etabolic engine that is the bod y’s largest sive saline ad ministration, limitation of intestinal electrolyte
barrier to the ou tsid e w orld . Yet it rem ains rem arkably losses due to ingestion of hypotonic fluids, and monitoring
resistant to infection, toxins, and neoplasm grow th. Diges- serum and urine electrolytes frequently are important steps
tive fu nctions—su ch as secretion of horm ones, enzym es, in management. An elemental or low residue diet and phar-
and electrolytes into the bow el lu m en—confer resistance to macological agents to slow intestinal transit time can be
infection and inju ry. Physical, imm u nologic, and p hysio- helpful. The value of exogenous trophic factors has not yet
logic barriers p rovid e key d efenses against infection and been adequately defined in human studies (6).
m alignant transform ation of cells. In fact, althou gh it com - If nonoperative management fails, operative interven-
p rises 90% of the entire gastrointestinal surface area, the tion can sometimes re-establish nutritional function and
sm all intestine p rod uces few er than 5% of gut tu m ors (1). relieve underlying pathology (Table 37.2). Restoration of the
Thus, the need for op erative intervention for intestinal fail- intestine’s nutritional role may be an anatomic, physiologic,
u re is frequ ently the result of a previous operation rather or combined effort. For example, placement of a colon inter-
than treatm ent of an intrinsic sm all bow el issue. position graft to interrupt peristalsis for patients with rapid
small bow el transit uses an anatomic alteration to correct a
physiologic problem. Surgical trad ition hold s that avoidable
■ INTESTINAL FAILURE
perioperative complications arise as a result of technical or,
Intestinal failure is “the red u ction in functioning gu t m ass more com monly, jud gment errors. Errors are prevented or
below the am ount necessary for ad equate d igestion and limited by clear goals, careful technique, and appropriate
absorp tion of food ” (2). This sim ple d efinition focu ses on alternative strategies. In addition, many less controllable fac-
the fu nctional role of the intestine, clarifying the p atho- tors can have an impact on short- and long-term complica-
p hysiology of nu m erou s possible und erlying m echanism s tions, such as age, functional status, und erlying d isease, and
of failu re, resu lting from even m ore num erous possible d is- severity of illness. Therefore, consid eration of specific preop-
ease states (Table 37.1). erative and intraoperative measures to reduce risk is critical.
Subacute or chronic failure results in slow ly escalating Previous surgical treatment plays a major role in the
d ebilitation due to the associated malnutrition. Wound heal- development of intestinal failure. In an extensive review of
ing slow s and stops w ithout ad equate am ino acid , carbohy- the literature, Tera and Aberg (7) determined that 1.6% of
d rate, fat, and vitamin and mineral substrates. Immunity is abdominal operations result in a reoperation and 34% to 43%
broad ly suppressed , includ ing neutrophil, T-cell, and anti- of reoperations result in mortality, a number confirmed by
bod y function. Longer-term markers like serum albumin are more recent studies (8–11). The two most common reasons
more useful for prognostication, w hile shorter-term markers for return to the operating room are peritonitis (32% of reop-
such as prealbumin or retinol-binding protein can assist erative cases) and ileus or obstruction (25% of cases). Other
w ith day-to-day assessment of nutritional repletion. Patients series (12,13) determined that adhesions after a previous
w ith unintentional weight loss of more than 10% to 15% of operation accounted for more than half of episodes of small
baseline bod y w eight or w ith a serum albumin level 3.0 are bowel obstruction; however, most episod es were successfully
severely malnourished. Prior to elective surgery, the most managed with nasogastric tube decompression. Thirteen
severely malnourished patients may benefit from preopera- percent to 38% of obstructed patients ultimately returned to
tive parenteral nutritional supplementation to reduce the the operating room after 6 to 8 days of unsuccessful decom-
perioperative risk of infection or nonhealing (3,4). pression, and risk increased w ith each subsequent operation.
Med ical therapy for intestinal failure aims to red uce the
severity of malnutrition, avoid complications, and maximize
■ PREOPERATIVE RISK MODIFICATION
Arden M. Morris: Associate Professor of Su rgery Chief, Prud ent planning for operation m u st includ e m axim izing
Colon and Rectal Su rgery University of Michigan p reop erative care d esigned to p revent com p lications. For
464
Chapter 37 • Complications of Intestinal Surgery: Small Bowel 465
Table 3 7 .1 Un d er lyin g et iologies of in t est in a l fa ilu r e

Etiology of Failure Mechanism Specific Disease Examples
Mechanical obstruction
Extrinsic compression Peritoneal adhesions, incarcerated hernia, extra-luminal mass
Stricture Crohn’s disease, ischemia
Torsion Postoperative, congenital malrotation
Obstruction Tumor, stool, gallstone, bezoar
Dysmotility
Ileus Postoperative, Narcotic use, Inflammation, Distal obstruction
Neuromuscular Acquired or congenital visceral myopathy, enteric neuropathy, disorder
Hemorrhage
Vascular Arteriovenous malformations, vascular-enteric fistula formation, ulceration
Tumor erosion Adenocarcinoma, carcinoid, lymphoma, gastrointestinal stromal tumor
Other erosion Meckel’s diverticulum
Necrosis
Chronic ischemia Atherosclerotic disease, radiation enteritis
Acute ischemia Thromboembolic disease, mesenteric torsion
Leak of intestinal contents (fistula, abscess, peritonitis)
Iatrogenic injury Unrecognized intraoperative injury, technical failure during anastomosis, ischemia
Anastomotic breakdown Inflammation, infection, malnutrition, immunosuppression
Spontaneous Ischemia, Crohn’s disease, postradiation, distal obstruction, tumor erosion,
ischemia, foreign body
Nutritional deficits
Malabsorption Previous ileal resection, Crohn’s disease, radiation enteritis, sprue, infectious
diarrhea, bacterial overgrowth
Short bowel syndrome Postoperative, Crohn’s disease, radiation enteritis, ischemic bowel
exam p le, p reop erative op tim ization of resp iratory and strate significantly im p roved p revention of p ostop erative
hem od ynam ic param eters m ay lim it perioperative m orbid - p u lm onary com p lications w ith the u se of incentive spirom -
ity and m ortality. In a rand om ized trial of norm al prep ara- etry (16). These d ata u nd erscore the u rgent need for w ell-
tion versus preoperative breathing exercises among upper d esigned clinical trials—and w e continu e to recom m end
abd ominal surgery patients at significant risk, postopera- p reop erative incentive sp irom etry training w ith consid -
tive pulmonary complication rate d ecreased from 60% to eration for p reop erative p hysiotherap y am ong high-risk
19% (14). Su bsequ ent w ork d emonstrated even better abd ominal su rgery p atients.
resu lts am ong abd om inal surgery p atients w ith preop era- Tim ely intervention for p reviou sly u nrecognized car-
tive incentive sp irom etry training and chest p hysiotherap y d iac arrhythm ias or p oorly controlled hyp ertension has
(15). By contrast, a recent m eta-analysis d id not d em on- been show n to red u ce p eriop erative risk of circu latory
em barrassm ent (17,18). A recent m eta-analysis d em on-
strated significant m ortality red u ction am ong high-risk
Table 3 7 .2 Th er a p eu t ic goa ls of p atients w ho received early op tim ization of hem od ynam ic
in t est in a l su r ger y p aram eters and oxygen d elivery, bu t no su ch benefit after
organ failu re had occu rred (19).
Restore nutritional role of small bowel
Recognition of barriers to healing is another part of the
Adequate length
Adequate lumen preoperative risk management process. The association
Adequate absorption between severe malnutrition and increased risk for postop-
erative complications or death are w ell established (Table
Relieve pathology
37.3) (20,21). The severely nutritionally d epleted patient can
Obstruction
Bleeding benefit substantially from 7 to 10 days of preoperative
Infection hyperalim entation. Comorbid d iseases associated w ith
Ischemia impaired microcirculation, such as renal failure and d ia-
betes, also inhibit mechanisms of healing and merit scrupu-
Prevent postoperative complications
Sepsis lous preoperative medical control. Glucocorticoids interfere
Obstruction w ith virtually every step in the phases of w ound healing. A
multivariate analysis of a large retrospective cohort rep orted
Table 3 7 .3 Im p a ct of n u t r it ion a l st a t u s on inju ries shou ld be rep aired w hen id entified . Other incid en-
p ost op era t ive com p lica t ion s a m on g tal lesions m ay be ad d ressed after correcting the p reop era-
in t est in a l fa ilu r e p a t ien t s tive issu e. Incid entally id entified tu m ors shou ld be excised .
Frozen section exam ination can be u sefu l to d eterm ine
Weight Postoperative benign versu s m alignant featu res and to ascertain clear
Degree of Loss Over Serum Complication m argins. Meckel’s d iverticu la shou ld be excised except in
Malnutrition 3 Months (%) Albumin Risk (%) m oribu nd p atients, accord ing to long-term p opu lation-
Mild 5–10 2.8–3.4 20–30 based d ata from the Mayo clinic (31). Anecd otally, incidental
Moderate 10–20 2.1–2.7 30–45 appendectomy has fallen into disfavor. While cumulative
d ata suggest prohibitive risk among patients w ho are more
Severe 20 2.0 40–60
than 50 years old , immunosuppressed , med ically unstable,
having prosthetic material or previous d iagnosis of Crohn’s
d isease, many stud ies support performing incid ental appen-
that long-term steroid u se w as the only variable associated d ectomy on patients less than 30 years old (32–35). Resisting
w ith a significantly higher rate of seriou s com p lications the urge to “tid y up” the abd omen is generally appropriate,
after anastom osis am ong Crohn’s patients (22). Cu m u la- lim iting the operation to the problem at hand .
tive d ata su ggest retinoid s and transform ing grow th factor
beta cou nter the steroid effect on collagen m etabolism ,
(23–25) bu t, in the absence of ad equate translational stu d -
■ Anastomosis
ies, neither has been incorporated effectively into clinical Much has been written and little resolved about anastomotic
practice. There has been consid erable d ebate regard ing the technique; stapled versus sutured, single layer versus dou-
operative risk associated w ith other immuno-suppressive ble layer, type of suture material, and impact of d iversion are
med ications such as infliximab, a recombinant anti-TNF all controversies still und er d iscussion. The goal of enteric
alp ha antibod y. An early p rospective stu d y fu nd ed by the anastom osis is to p revent leakage, p rom ote healing, p re-
manu factu rer ind icated m inim al operative risks beyond serve bow el length, and p revent strictu re form ation. An
those alread y faced by Crohn’s d isease patients (26). A effective anastom osis requ ires ad equ ate m obilization, p er-
larger retrospective stu d y d em onstrated significantly fu sion, apposition, and inversion of the mucosal ed ges into
increased risk of p ostoperative sepsis, abscess, and read - the bow el lumen. H ealing depend s on approximation of the
missions in Crohn’s patients treated w ith inflixim ab w ithin collagen-containing submucosal layer. Inadequate perfusion
3 m onths p rior to op eration, as com pared w ith inflixim ab or tension across the anastomosis may cause early leakage or
naïve p atients (27). These results are in contrast to another late stricture formation.
retrosp ective stu d y (28). Given the p otential for selection Anastom otic leakage is a potentially d isastrous com p li-
bias am ong even carefu lly cond u cted retrospective stu d ies, cation, running the gamut from a contained self-limited
prospective d ata w ould be especially useful to ad d ress the event to sepsis and abd ominal catastrophe (9–11). Covering
qu estion of best p ractice w ith regard to avoid ing inflixim ab the anastom osis w ith om entum m ay contribute to preven-
preoperatively. tion or containm ent of leakage. Investigations into the fre-
quency of leakage after stapled versus sew n anastomoses
are contrad ictory; available d ata sup port the su periority of
■ INTRAOPERATIVE TECHNICAL ISSUES each and of neither (36,37). Current American College of
Evid ence-based recom m end ations for intraop erative tech- Su rgeons-sp onsored efforts to record , analyze, and im prove
niqu e to prevent postoperative com p lications largely rest p ostoperative ou tcomes may shed further light on these d if-
upon H alsted ’s early tenets to hand le tissue gently, emp loy ficu lt analyses. It is also plau sible, how ever, that national
aseptic techniqu e, avoid closing u nd er tension, and close registries m ay be lim ited by inad equ ate d ata capture in the
w ound s com p letely w henever possible. Lim iting intra- trad itional 30-d ay postoperative w ind ow. An im portant
abd om inal d issection to that required for ad equ ate exp o- recent stu d y of anastomotic leaks revealed that 12% w ere
su re and hand ling tissu e gently w ill help to p revent serosal d iagnosed after the 30(th) p ostoperative d ay and 42% w ere
injury and limit blood loss, thereby restricting ad hesion d iagnosed only after read m ission to the hospital (38).
form ation (29,30). Massive ad hesions and herniations can Anastom otic strictu res form as a resu lt of ischem ia, ten-
lead to loss of abd om inal d om ain, a vexing intraop erative sion, or infection d u e to p reviou s anastom otic failure. Tech-
problem that m ay requ ire u se of mesh or relaxing incisions nical choices are fairly forgiving bu t m ay also p lay a role. In
to close w ithou t tension. a rand om ized controlled trial of esop hagogastrostom y
anastom oses, a d ou ble-layer closu re led to significantly
m ore strictu re form ation than single layer (39). Mu ch of the
■ Exploration remaining research ad d ressing anastomosis is lim ited to
Du ring exp loratory lap arotom y of a nonhostile abd om en, the colon and rectal literatu re, w hich has lim ited ap plica-
initial evalu ation of the sm all bow el consists of exam ination to sm all bow el issu es. The p rincip les of a safe anasto-
tion from the ligam ent of Treitz to the cecum . Serosal m osis can be observed u sing a variety of techniqu es.
■ Mesenteric defects nist alvim op an rem ains u ncertain bu t w ill likely be clarified
w ith larger multi-center trials. If the ileus is prolonged more
Literature ad d ressing closu re of m esenteric d efects is also than 7 d ays in a patient w ith previously normal motility, an
scarce. Cu stom arily, an absorbable sutu re incorp orating early m echanical obstruction or p ossible enteric leak shou ld
only the p eritoneal leaves of d ivid ed m esentery is ru n from be consid ered (48–50). Timing of reop eration becomes espe-
the ap ex of the d efect tow ard the bow el. With the ad vent of cially relevant d uring the 2 to 6 w eek postoperative w in-
lap aroscop ic colon resection, the utility of m esenteric clo- d ow, w hen extensive ad hesions and inflammation create a
su re has been qu estioned and the techniqu e sim p ly aban- significant technical challenge increasing the risk of bleed -
d oned by som e. H ow ever, m any surgeons elect to close ing, fistu la, abscess, and abd om inal sepsis (8).
d efects sm all enou gh to potentially incarcerate bow el.
■ Adhesion prevention ■ SPECIFIC INTESTINAL DISORDERS

REQUIRING INTERVENTION
Placem ent of a bioresorbable ad hesion barrier over abd om -
inal contents prior to anterior w all closu re can lim it or even Although the potential com plications of intestinal su rgery
p revent p ostop erative abd om inal w all ad hesion form ation are myriad , they tend to be closely related and even over-
(40–42). This is an esp ecially u sefu l exercise for p atients lap p ing (Fig. 37.1). Many u nd erlying d iseases pred ispose
w ith tem p orary ileostom y or other anticip ated fu tu re to p articu lar p ostop erative issu es. This section exam ines
lap arotom y. Wrap p ing a fresh anastom osis in su ch an the com plications that arise m ost frequently after operative
ad hesion barrier resu lts in a higher leak rate and is d is- intervention for sp ecific u nd erlying d iseases or cond itions.
cou raged (43). Ad d itionally, several case rep ort stu d ies
d escribe a rare, intense, nonsep tic p eritonitis reaction fol-
low ing ap p lication of Sep rafilm (44–46). This m anifests as
■ Short bowel syndrome
a high fever w ith severe d iffu se abd om inal p ain in the Short bow el synd rom e d escribes a constellation of sym p-
early p ostop erative p eriod , necessitating retu rn to the tom s inclu d ing malnu trition, w eight loss, steatorrhea, and
op erating room and most frequently resulting in a negative d iarrhea, resu lting from inad equ ate absorp tive gut surface
exploratory laparotomy. The etiology of this process remains area. The d isord er m ay follow m assive intestinal resection
unclear bu t anecd otally it arises m ost com m only am ong for ischem ia, infection, m esenteric d esm oid tu m ors, or
Crohn’s d isease patients. N o d ata are available from the other d iseases. Short bow el synd rom e m ay be the cum u la-
manu factu rer w ith regard to this p henom enon. tive effect of sequ ential excisions or the fu nctional resu lt of
p roxim al fistu la form ation. Althou gh ind ivid u al variation
and ad ap tation can occu r, m ost p atients w ith less than 100
■ Ileus cm total bow el or less than 150 cm w ithou t the ileocecal
Postop erative ileu s is a p red ictable bu t p oorly u nd erstood valve w ill not survive w ith enteric nu trition alone.
p henom enon, w hich generally lasts 3 to 5 d ays and is In ad d ition to the exp ected com p lications of m alnu tri-
m anaged expectantly. A recent review (47) has id entified tion, other associated com p lications inclu d e cholelithiasis,
laparoscopy, thoracic epid ural anesthesia, avoid ance of opi- nep hrolithiasis, and gastric hyp ersecretion. Sym ptom atic
oid s, and early feed ing as potential interventions to limit cholelithiasis d evelops in 20% to 40% of patients, and is
ileus d uration. N asogastric d ecom pression d oes not red u ce most frequent in those dependent on parenteral nutrition. In
ileus d u ration. Effectiveness of the selective opioid antago- review s of the topic, Thompson recommends considering
Mechanical obstruction
Short gut syndrome

Incarcerated hernia
Adhesions
Fistula
Stricture Torsion
Peritonitis Ischemia
Enteric leakage
Injury
Abscess Ileus
FIGURE 37.1. Schematic association of
common postoperative complications.
Midline incision
er '04
h
HRFisc
FIGURE 37.2. Measuring the small bowel (short gut).
prophylactic gall blad d er excision p rior to the d evelop - Op erative treatm ent of short bow el synd rom e consists
ment of hep atic changes, d ense ad hesion form ation, and of p roced u res to relieve obstru ction, increase bow el surface
med ical com p lications of m alnutrition (51,52). N ephrolithi- area, and slow transit tim e. Relief of obstru ction is u su ally
asis arises in abou t 25% of patients w ith som e retained achieved by strictu rop lasty and is m ost relevant in the
colon, d u e to increased colonic oxalate absorption and Crohn’s d isease p atient. The m ost u sefu l m ethod for
excretion throu gh the urinary system . Calciu m oxalate increasing the absorptive su rface is reconstru ction of
stone form ation m ay be prevented by carefu l d iet m anage- d efu nctionalized bow el. Althou gh reap p roxim ation of the
ment and cholesterol bind ing m ed ication (53). Gastric sm all intestine and colon increases su rface area and p ro-
hyp ersecretion after m assive bow el resection is poorly vid es a trop hic effect, it can also exacerbate d iarrhea and
und erstood and u su ally tem porary, bu t can lead to p ep tic stone form ation. Tap ering and lengthening p roced u res
ulcer d isease requ iring u se of proton pum p inhibitors (54). im p rove absorp tion and m otility, and have been m ost
Efforts to p revent and m anage short bow el synd rom e extensively u sed in p ed iatric p atients (59,60). Transit slow -
have ad vanced su bstantially in the p ast tw o d ecad es. Pre- ing p roced u res have been less su ccessfu l. Creation of an
vention is the forem ost treatm ent strategy, esp ecially antip eristaltic segm ent has had variable efficacy. Interposi-
w hen fu tu re abd om inal op erations are anticip ated . In tion of a colonic segm ent has show n p rom ising resu lts in
cases of viable bu t obstru cted bow el, lim iting the extent of som e rep orts bu t led to obstru ction and failu re in others
resection and p erform ing strictu rop lasty have becom e (51,52,61).
stand ard s of care. Measu rem ent of rem aining bow el is Refractory short bow el d isease, w hether anatom ic or
easily p erform ed before closing the abd om en (Fig. 37.2), p hysiologic, requ ires nu tritional su p p ort and consid era-
and facilitates d iagnosis of related d isord ers and p lanning tion of transp lantation (62). H yp eralim entation has becom e
of fu tu re therap y. increasingly sop histicated since its introd u ction in 1968,
Effective m ed ical treatm ent for short bow el synd rom e bu t is associated w ith m any inherent p otential com plica-
im proves absorption of nutrients and slow s intestinal tran- tions. These w ill be ad d ressed in d etail in a sep arate chap -
sit tim e. Postop erative m ucosal hyperplasia occu rs over a ter. For p atients in w hom hyp eralim entation has been
period of 6 to 12 months. Early reports suggested that glu t- frau ght w ith com p lications, intestinal transp lantation m ay
amine and grow th horm ones enhance m ucosal ad ap tation, be an op tion. Several stu d ies now ind icate outcom es
bu t these d ata have not been replicated in w ell-d esigned ap p roxim ating those of lifelong total p arenteral nu trition,
subsequ ent stu d ies (55–57). An elem ental, high-carbohy- if the transplant can be accom plished prior to the onset of
d rate, low -fat d iet m ay have a trophic effect and im p rove hep atic cirrhosis (63–65).
absorp tion (56). Agents that slow bow el transit are stap les
of therap y. Lop eram id e d ecreases intestinal m otility and
secretion and has been show n to increase sp hincter p res-
■ Crohn’s disease
sure; (58). In the su fficiently im paired patient, cod eine or Crohn’s d isease is a chronic, segm ental, transm u ral, T
tincture of op iu m m ay be necessary. Octreotid e m ay p rove h elp er cell-m ed iated d isease th at can arise an yw here in
useful if transit is too rapid or the intestine is too short for th e gastroin testin al tract an d variou s extrain testin al
absorp tion of oral antisecretory m ed ication. organs. Sym p tom atic hallm arks inclu d e d iarrhea, w eight
loss, and abd om inal p ain. Seventy p ercent of Crohn’s Iatrogenic short bow el synd rom e is one of the m ost
p atients overall and 84% of those w ith ileocecal d isease notoriou s and challenging comp lications of operating for
requ ire su rgical intervention at som e tim e (66). Solid Crohn’s d isease. Short bow el synd rom e is of particu lar
d ata is lim ited regard ing the im p act of p reop erative concern among Crohn’s patients d u e to their comm on p res-
im m u nosu p p ressive m ed ication on p ostop erative com - entation w ith term inal ileal d isease, necessitating ileocecal
p lication rates am ong Crohn’s p atients. Steroid u se has valve resection. Patients are su bject to d ehyd ration, exacer-
been associated w ith greater risk in som e large retrosp ec- bation of d iarrhea, and inad equ ate nu trition for healing
tive series (22,67) bu t not others (68,69). Preop erative and health m aintenance. Strictu rop lasty for preserving
treatm ent w ith nonsteroid im m u nosu p p ressives has bow el length in Crohn’s d isease p atients is essential to
actu ally been associated w ith better p ostop erative ou t- long-term outcom e and is review ed in d etail below.
com es (26,69).
Acu te or chronic obstruction, fistu la or abscess form a- Fistula Formation
tion, and com p lications of previou s operations are the m ost Spontaneou s intra-abd om inal abscesses and fistu lae form
com m on ind ications for operation. Short bow el synd rom e, in 20% to 40% of Crohn’s patients and are a fund amental
fistu la form ation, and d evelopm ent of an abd om en so rife characteristic of the d isease. Postoperative fistula formation
w ith ad hesions that it m u st be consid ered frankly hostile occu rs in about 10% to 15% of patients in the 30-d ay periop-
are am ong the m any potential com plications of op erating erative period , (22,67) bu t in more than 20% over the ensu-
in this setting. ing 5 years (70). Either may be id entified preoperatively
based on sym p tom s and rad iologic stu d ies, or id entified
Malabsorption incid entally w hile examining the bow el d uring laparotomy.
Malabsorp tion and d iarrhea, intim ately related m anifes- Appropriate therapy is based on the clinical situation. Licht-
tations of Crohn’s d isease, m ay resu lt in a fu nctional enstein’s review of med ical therapy reports encouraging
short bow el syn d rom e bu t are also cau sed by an anatom - early results w ith use of infliximab, but acknow led ges fre-
ically short gu t d u e to m u ltip le resections. Micronu trient quent need for surgical intervention (71). Treatment of
m alnu trition d ep en d s on th e an atom ic site an d length of sym ptom atic fistu lae inclu d es resection of the fistulizing
bow el resection. Cyanocobalam in (vitam in B12) is the bow el and tract, w ith simp le closu re of the involved nond is-
m ost com m on d eficien cy an d occu rs p red ictably after eased viscus. No intervention is w arranted for spontaneous,
resection of 50 to 60 cm of term inal ileu m . Folate d efi- asymptomatic enteroenteric fistu la formation (72).
ciency resu lts from resection or d isease of the p roxim al Man agem ent of an en terocu taneou s fistu la is based
jeju n u m . Dim in ished absorp tion of fat solu ble vitam ins on sym p tom s, d u ration, an d , m ost im p ortantly, ou tp u t
(A, D, E, an d K) m ay occu r w ith red u ced absorp tion of (Table 37.4). Preliminary therapeutic goals are treatment of
bile salts, con tribu tin g to a h ost of sequ elae in clu d in g sepsis, skin protection, accurate ou tpu t m easurem ent, and
calciu m d eficien cy, osteop orosis, bleed in g d iath eses, ascertainment of ad equ ate nu trition. Spontaneous closure is
and oth ers. p ossible d ep end ing p rim arily on the cau se, location, related
Table 3 7 .4 M a n a gem en t of en t er ocu t a n eou s fi st u la e
Management Likelihood of
Spontaneous Mortality
Quantity/24 hr Early Late Resolution (%)
Low output 200 cc Bowel rest, Nutrition repletion, After 30–40 days: Moderate 5
Skin protection, Appropriate Consider curettage
drainage of tract, Instillation of
noxious substance
or fibrin glue, or
Resection of tract
with primary closure.
Medium output 200–500 cc Bowel rest, TPN, Skin or After 40–90 days or Low 30
wound protection, Drainage resolution of sepsis:
of sepsis Consider diversion
with delayed repair
versus resection.
High output 500 cc Diversion, TPN, Skin or wound After 40–90 days or None 35–50
protection including consideration resolution of sepsis:
of vacuum-assisted closure, Resection with
Drainage of sepsis temporary diversion
Table 3 7 .5 Fa ct or s p r even t in g sp on t a n eou s d etected preoperatively based on computed tomography

fi st u la closu r e (CT) or sm all bow el contrast stud ies. Fibrosis may be id enti-
fied d uring intraoperative bow el examination. At these sites,
Sepsis the sm all bow el appears and feels thickened and firm. Prox-
Distal obstruction imal bowel may appear distended with a smooth edematous
or thickened w all. If access to the lum en has alread y been
Radiation injury
obtained , a balloon catheter d istend ed to 2.5 cm may be
Mucosal eversion at the skin level pulled from the ligament of Treitz to the cecum to assess the
High output/proximal fistula luminal diameter. Sometimes even areas of intestine that
Poor nutrition appear normal externally will reveal a narrow lumen w ith
extensive internal fibrotic strands.
Short strictu res can be d ilated w ith the catheter balloon.
Longer strictu res or those w ith extensive fibrosis are best
infection, and nu tritional statu s (Table 37.5). Proxim al fistu -
m anaged by resection or strictu rop lasty (Fig. 37.3). The
lae are associated w ith a higher d aily ou tput and nutri-
ju d gm ent for resection versu s p reservation w ith strictu ro-
tional d eficiency (a fu nctional short gu t); d istal fistu lae are
p lasty is based u p on the length, p roxim ity, and overall
more likely to have a low er ou tput and to heal sponta-
nu m ber of strictu res, and on the length of rem aining short
neously. Low to m od erate ou tput enterocutaneou s fistu lae
bow el. The risk of strictu re recu rrence is high. At least 30%
( 200 cc/ d ay and 200 to 400 cc/ d ay, resp ectively) m ay be
of Crohn’s p atients op erated on for acu te d isease w ill
managed by observation, consid eration of bow el rest, and
requ ire at least one ad d itional op eration for obstru ction.
p arenteral nu trition if ind icated . Som e au th ors ad vocate
cu rettage of the fistu la tract, w ith or w ithou t fibrin glu e Recurrence
insertion, or instillation of a noxiou s su bstance to facili-
Perhaps the most common complication of operating for
tate scar form ation, su ch as p henol. Rep orted ou tcom es
Crohn’s d isease is Crohn’s recurrence. Asymptomatic endo-
are highly variable and largely based on sm all series w ith
scopic evidence of disease has been reported as early as 3
p oorly qu antified follow -up.
months postoperatively and in up to 75% of patients within
Obstruction the first postoperative year (75,76). Data regarding the influ-
ence of end oscopically id entified d isease on d evelopment of
Intestinal obstru ction in the Crohn’s p atient generally
symptoms requiring operation are inconclusive. The extent
begins as an acu te inflam m atory process, best controlled by
of resection does not appear to have an impact on recur-
im m unosu p p ressive m ed ication if p ossible. If m ed ical
rence; w hile macroscopic disease should be removed, the
therapy is ineffective after 7 to 10 d ays or if acute obstruc-
presence of resid ual microscopic d isease has no correlation
tion repeated ly recurs, operative resection or bypass should
w ith symptomatic recurrence. Inconsistent d ata have made
be consid ered (73,74). There is no need to resect beyond
clear identification of risk factors d ifficult (70,77) (Table 37.6).
macroscop ically non-involved bow el, and a conservative
Prophylaxis against recurrence using med ical therapy has
app roach to resection has d ecreased the incid ence of p ost-
been d isappointing overall, but several w ell-d esigned stud -
operative short bow el synd rom e in recent years. Record ing
ies of new er med ication are currently und erw ay.
the m easu red bow el length in the op erative note w ill help
w ith fu tu re treatm ent p lanning.
In contrast to the inflammation, adhesions, and abscesses
■ Irradiated bowel
observed in an acute Crohn’s d isease obstruction, chronic Many of the com p lications resu lting from rad iation inju ry
obstruction is primarily a fibrotic process. Strictures m ay be to the sm all bow el are rem iniscent of Crohn’s d isease,
Table 3 7 .6 Risk fa ct or s for p ost op era t ive r ecu r r en ce of Croh n ’s d isea se

Factor Impact on Clinical Recurrence
Patient-related factors Age Mild increase in recurrence.
Gender No impact on recurrence.
Smoking Independent risk factor for recurrence with odds ratio 2–4 compared to nonsmokers.
Odds are especially high among women who smoke.
Disease-related factors Location of disease Data have suggested increased recurrence with ileocolonic disease, but are inconclusive.
Duration of disease No impact on recurrence.
Surgical factors Margin Histologic evidence of residual Crohn’s has no impact on recurrence.
Anastomotic method No impact on recurrence.
Diversion of the fecal Specific toxins or antigens the feces have not been identified, but lack of diversion and
stream reversal of diversion appear associated with higher recurrence rates.
2 cm 2 cm
A Heineke-Mickulicz
B Finney
FIGURE 37.3. Bowel-preserving techniques for management of intestinal strictures. A: Heineke-Mickulicz stricturoplasty. A longitudi-
nal incision is created sharply in the antimesenteric wall to 2 cm beyond the proximal and distal boundaries of the stricture. Two 3–0 silk
stay sutures are placed on either side of the incision at the midpoint and retracted to reorient the incision to transverse. A single layer of
full-thickness 3–0 silk interrupted sutures is placed to reapproximate the bowel edges in the new transverse orientation. B: Finney stric-
turoplasty. The Finney technique is advised for very long ( 25 cm) strictures of the small bowel. A longitudinal incision is created sharply
in the antimesenteric wall. A stay suture placed at the apical midpoint is retraced to facilitate an upside-down U orientation. The inner
edge is sutured to itself longitudinally from the luminal side to become a new posterior wall, with the previous distal-most bowel now
abutting the proximal-most bowel. Similarly, the outer edge of the U is closed with simple interrupted full-thickness suture to become the
new anterior wall.
su ch as strictu re (obstru ction), chronic bleed ing, d iarrhea, w ith low er short-term com p lication and m ortality rates
m alabsorp tion, fistu la form ation, and abd om inal p ain. (Table 37.7). Longer-term issu es arising from byp ass
One m ay infer from the broad variety of interventions inclu d e ongoing fibrotic strictu re form ation, bacterial
d esigned to slow m otility and enhance absorp tion that overgrow th, and issu es of chronic m u cosal d am age (79).
su rgical therap y has lim ited efficacy. H ow ever, a sym p - One sm all series rep orted encou raging resu lts u sing stric-
tom –d irected op eration m ay be u navoid able and in this tu rop lasty for long-segm ent rad iation-associated obstru c-
setting the extrem e fragility of irrad iated bow el m u st be tion (80). The im p ortance of cau tiou s consid eration of
resp ected . Resection and byp ass are the fou nd ations of op erative goals and alternative strategies is w id ely recog-
su rgical therap y. Com p lication rates are high, w ith anas- nized . Becau se rad iation d am age and obstru ctive sym p -
tom otic leakage rates u p to nearly 60%, p robably d u e to tom s can continu e to m anifest som etim es over d ecad es,
com p rom ised p erfu sion (78). Althou gh the valu e of resec- p reserving bow el length even in the initial op eration is
tion versu s byp ass has been d ebated , byp ass is associated recom m end ed .
Table 3 7 . 7 Post op er a t ive m or t a lit y a ft er in t er ven t ion for ir ra d ia t ed in t est in e

Source Bypass n Mortality (%) Resection n Mortality (%)
Joelsson and Raf (108) — — 19 16
Swan et al. (109) 28 7 17 53
Schmitt and Symmonds (110) 20 0 65 9
Lillemoe et al. (111) 11 0 6 17
Wobbes et al. (78) 20 10 7 57
Galland and Spencer (112) 2 0 18 44
Total 81 5 132 23
■ Intussusception ■ Neoplasms of the small bowel

Intu ssu scep tion , or telescop ing of the bow el, is a rare Tum ors of the sm all bow el are rare and tend to be d iag-
event u su ally id entified by a sym p tom s of bow el obstru c- nosed at ad vanced stages d u e to nonsp ecific sym p tom s
tion and a CT scan revealing an asym m etrical target sign and d ifficu lt access. The m ost com m on p resenting sym p-
(Fig. 37.4). In contrast to the p ed iatric p atient, in tu ssu s- tom s are p ain, anemia, and w eight loss. Abou t half of
cep tion in the ad u lt is m ore frequ ently d u e to an tu m ors are fou nd in the jejunu m; the rem aind ers are evenly
an atom ic lead p oin t abnorm ality, su ch as a tu m or, thu s sp lit betw een the d u od enu m and the ileu m . The resectabil-
trad itionally treated by exp loratory celiotom y and p roba- ity rate is high; how ever, 1- and 5-year su rvival rates are
ble resection (81). Potential com p lications of su ch inter- less encou raging (Table 37.8). In a 10-year series, N aef and
vention are the u su al p ostop erative ileu s, bleed ing, others rep orted that 71% of all sm all bow el tu m ors w ere
infection, d am age to nearby stru ctu res, and ad hesion for- malignant and 62% had alread y metastasized at the time of
m ation . Delay in op eration for incarcerated intu ssu s- d iagnosis (83). Major postoperative comp lications occurred
cep ted bow el can lead to ischem ic necrosis. H ow ever, an in 24% of patients; 4% required reoperation for anastomotic
interesting artifact of im p roved CT technology has led to leaks, and 4% d ied .
a new p ossible com p lication of su rgery for d iagn osis of
intu ssu scep tion: u nnecessary exp loratory lap arotom y. Benign Neoplasms
H igh resolu tion circu lar CT has becom e so rap id an d Benign neoplasms of the small bow el are uncommon and
im ages are so clear that bow el seen end -on m ay be cap - typically discovered incidentally during laparotomy for
tu red d u ring p eristalsis, p otentially resu lting in a d iag- another p u rp ose. Althou gh all m ay occu r sp orad ically,
nosis of in tu ssu scep tion that d oes not actu ally requ ire many are associated with specific underlying diseases. For
intervention. A large single institu tion review id entified example, hamartomas are associated w ith Peutz-Jaegers
intu ssu scep tion length of less than 3.5 cm to be a reliable syndrome and Cronkite-Canad a synd rome; hemangiomas
p red ictor of a self-lim iting p rocess (82). Th u s far, no are associated w ith Osler-Weber-Rend u synd rome; and ad e-
p rosp ective test of criteria for n onop erative intu ssu scep - nomas are associated w ith familial ad enomatous polyposis
tion has been p erform ed . syndrome. Resection of symptomatic tumors or tumors
FIGURE 37.4. Computed tomography scan

revealing an asymmetrical target sign pre-
viously considered the sine qua non of small
bowel intussusception. This asymptomatic
patient was referred for further evaluation
of incidentally identified “intussusception.”
Asymmetrical target sign

Table 3 7 .8 N eop la sm s of t h e sm a ll in t est in e: in cid en ce a n d p rogn osis

1-Year 5-Year
Tumor Type Incidence Examples of Associated Syndromes Survival Survival
Leiomyoma 75% Spontaneous
Adenoma 17% Familial adenomatous polyposis
Hamartoma 8% Peutz-Jaegers, Cronkite-Canada
Hemangioma 1% Osler-Webber-Rendu
Lymphangioma 1% Spontaneous
Other 1%
Total benign 12/54 (22%) 67% 50%
Adenocarcinoma 33% Familial adenomatous polyposis
Carcinoid tumor 17% Multiple Endocrine Neoplasia I,
Von Hippel-Lindau, Neurofibromatosis-1
Gastrointestinal stromal tumor 17% Spontaneous
Non-Hodgkins Lymphoma 12% Spontaneous
Melanoma 9% Dysplastic Naevus syndrome
Other 12%
Total malignant 42/54 (78%) 43% 21%
Adapted from Naef M, Buhlmann M, Baer HU. Small bowel tumors: diagnosis, therapy and prognostic factors. Langenbecks Arch Surg 1999;384(2):176–180.
w hich are d ysplastic can be performed end oscopically, vague abd ominal pain and weight loss. Carcinoid tumors
through an enterotomy w hich should then be closed trans- generally prod uce symptoms d ue to ischemia from mesen-
versely, or by limited local excision w ith end-to-end anasto- teric microvascular invasion, d esm oplasia, and lym-
mosis. Resection of isolated asymptomatic benign lesions is phed ema from metastases to draining lymph nodes. Fibrosis
reasonable in the setting of intra-abd ominal examination. can extend to the root of the mesenteric vessels creating a
How ever, resection of numerous asymptomatic benign major technical challenge to resection, and potentially m an-
tumors is not w arranted , d ue to the limited benefit and ad d i- d ating bypass to avoid massive intestinal ischemia.
tive complication risk of each enterotomy. Carcinoid synd rom e occu rs in abou t 10% of patients
w ith m id gu t carcinoid s, and frequ ently ind icates hepatic
Adenocarcinoma
involvem ent. A carcinoid synd rom e “attack” is m ed iated
Adenocarcinoma is the most common malignancy of the by neu rotransm itters, horm ones, and p ep tid es released by
small intestine, accounting for about one-third of cases. Ad e- the tu m or cells. The hu m oral p rod u cts stim u late vasom o-
nocarcinoma may occur sporad ically or in association w ith a tor changes, bronchosp asm , gastrointestinal hyperm otility,
defined polyposis syndrome. Adenomas and adenocarcino- and hyp otension.
mas of the small bow el are not associated w ith particularly Carcinoid crisis is a potentially fatal carcinoid synd rome
high complication rates; how ever, lesions due to underlying attack, w ith pronounced changes in blood pressu re, d iar-
Gard ner ’s synd rome may have associated desmoid tissue. rhea, confu sion, bronchoconstriction, card iac arrhythmia,
Desmoid tum ors, a histologically benign but behaviorally and hyperthermia. Carcinoid crisis may occur spontaneously,
malignant process, are a cause for grave concern. They are during induction of anesthesia, while handling tumor in the
composed of fibroblasts grow ing in thick, w hite plaques operating room, or during hepatic arterial embolization or
w hich grad ually surround , contract, and compress viscera chemotherapy treatment. Octreotide, and histamine blockers
and vessels. Desmoid tumors are akin to biological cement, as well as supportive care must be administered immediately.
inexorably filling the peritoneal cavities of these unfortunate
Gastrointestinal Stromal Tumor
patients. No real cure or prevention has been identified,
although estrogen and nonsteroidal anti-inflammatory med- Gastrointestinal strom al tu m ors (GISTs) have cap tu red
ications have shown limited efficacy. Operative intervention scientific and clinical attention in recent years d u e to
should be und ertaken cautiously. m ajor ad vances in u nd erstand in g of p ath op hysiology
and treatm ent. These tu m ors w ere often m iscategorized
Carcinoid Tumor as sarcom as p reviou sly, bu t now are believed to d erive
Carcinoid tumors originate from neuroend ocrine tissue and from the in terstitial cells of Cajal, th e intrinsic p acem ak-
can be sporad ic or associated w ith a num ber of fam ily cancer ers cells of th e gu t. Com p lication s arisin g from resection
synd romes. Patients typically present w ith complaints of are p red ictable: an astom otic leakage, strictu re form ation,
ad hesion s. When m alignant, th ese cells tend to m etasta- d iagnostic testing, and ju d gm ent regard ing the ad vantages
size hem atogen ou sly and to recu r either locally (p ossibly of resection versu s observation.
d u e to inad equ ate m argins) or in the liver. Identification of an intestinal bleeding source can be diffi-
cult due to its infrequent and usually intermittent occurrence,
Exogenous Tumors the length of the small intestine, and the paucity of sensitive
End ometriom as are benign collections of end om etrial tis- tests. Traditionally, after upper and low er end oscopy, evalua-
su e w hich have sp read ou tsid e of the fem ale rep rod u ctive tion of a suspected small intestine bleeding source begins
anatom y. They can resu lt in ad hesion form ation, ill-d efined with a small bow el X-ray, w hich is only diagnostic in 5% to
abd om inal p ain, obstruction, and can even erod e throu gh 10% of cases (85,86). The technetium-99 labeled red blood cell
the bow el w all resu lting in bleed ing into the lum en. In gen- scan is a more sensitive diagnostic test and carries few risks
eral, end om etriom as can be treated med ically and tend to beyond tim e d elay. Ad d itionally, as long as no transfusion
reced e d u ring the p ostm enop au sal p eriod . is requ ired , the tagged cells w ill rem ain p ositive for 12 to
Intrap eritoneal m etastases from nonintestinal sites are 24 h ou rs, permitting delayed testing. Although this test can
rem iniscent of d esm oid tu m ors, and are best d iagnosed by help to diagnose blood loss w ithin the small intestine, pooled
CT or p ositive em ission tom ography scan. Su ch lesions blood can be d eceptive. Localization of the exact bleeding site
portend a d ism al p rognosis; operation for minim al gain is difficult unless the site has specific anatomic features, as in
that confers su bstantial risk should be avoid ed . H ow ever, the d uodenum or terminal ileum. Angiography can help to
palliative intervention such as enteroenteric bypass or sim - localize a lesion bleeding at 0.5 mL/ min but is less than
ply gastrostom y d rainage m ay be ind icated . 50% sensitive if bleed ing has slowed or stopped. Moreover, a
major advantage of angiography, its therapeutic value, is lim-
ited in the small, branching arcad es of the small intestine. For
■ Hemorrhage slow er or more obscure sources of small bowel blood loss,
Intestinal hem orrhage betw een the d u od enal bu lb and the capsule endoscopy has become the standard localizing test. A
ileocecal valve accou nts for 3% to 5% of bleed ing from the small wireless endoscopic capsule is swallowed and takes
gastrointestinal tract, (84) bu t m ay be cau sed by a greater two pictures of the lumen per second. Recording devices
variety of lesions than in the entire rem aining bow el (Table worn by the patient capture images and track the route of the
37.9). Prevention of com plications of surgery for intestinal capsule for localization, with generally acceptable sensitivity
hem orrhage is based u pon tim ely d iagnosis, app rop riate and specificity (87,88).
Table 3 7 .9 Et iologies of sm a ll in t est in a l bleed in g

Causes of Intestinal Bleeding Location Features
Vascular lesions
Angiodysplasias or vascular ectasias Throughout, but most concentrated in Mucosal and submucosal dilated arterial vessels
the right colon
Telangiectasias Throughout the intestine Full thickness dilated vessels, diffuse
Arteriovenous malformations Throughout Thick-walled arteries and veins without intervening capillaries
Vascular anomalies
Small bowel varices Duodenum, proximal jejunum Associated with prehepatic portal hypertension
Aortoenteric fistula Duodenum, ileum Herald bleeding followed by massive hemorrhage.
Dieulafoy lesion Fundus, duodenum, jejunum Painless, massive bleeding
Vasculidities
Collagen-vascular diseases Large and small arterial compromise
Venulitis Mucosal edema, malabsorption, ulcerations
Radiation damage Mucosal edema and ulcerations
Ulcerations
Crohn’s disease Throughout Transmural ulceration, bleeding is usually indolent
Gastrinomas Duodenum, jejunum
Infection associated Throughout
Medication induced Throughout
Meckel’s diverticulum 100 cm proximal to the ileocecal valve Ulceration and brisk bleeding due to ectopic gastric mucosa
within the diverticulum.
Pseudo-diverticula Jejunum Mesenteric border of the intestine, unlikely to be a source of
blood loss but may bleed massively
Small bowel tumors (see above)
Exp loratory surgery m ay be excessively invasive but ■ Small intestinal bypass

has both d iagnostic and therapeu tic valu e. Becau se m any
of the cau sative lesions are flat or sm all and thu s hard to Defunctionalization of som e portion of the sm all intestine
palpate, exp loration is best accom panied by d iagnostic can occu r d u e to enteroenteric fistu la, bu t is m ore com -
end oscop y of the sm all bow el. Intraoperative enteroscop y, m only the resu lt of op erative intervention. Su rgical bypass
termed “p u sh enteroscop y,” requ ires ad vancem ent of a is categorized as therap eu tic for w eight loss or p alliative
colonoscop e or som etim es a sp ecialized enteroscop e u nd er for obstru ction. While intestinal byp ass for either p urpose
d irect visu alization w ith m echanical assistance. Localiza- carries sim ilar op erative risks, the u nd erlying d isease
tion of the bleed ing site occu rs in 38% to 75% of cases and p rocess has a m ajor im p act on long term ou tcom e. Several
m any lesions can be treated end oscopically (89). late com p lications of d efu nctionalized bow el or “blind
Tim ing of an operation requ ires jud iciou s planning. loop s” have been id entified . Bacterial overgrow th d ue to
After the initial presentation, m any vascu lar lesions red u ced or absent peristalsis and d iversion of d igestive
d emonstrate no fu rther bleed ing. Angioectasias rep resent juices can lead to form ation of m etabolites toxic to the
80% of bleed ing lesions in patients over age 60, bu t only intestinal m u cosa, p oor nu trient absorp tion, intractable
rebleed in 10% of cases (90). In contrast, sm all bow el d iarrhea and resu ltant m echanical trau m a. Diagnosis is
tumors, the m ost com m on sou rce of sm all intestinal bleed - u su ally based on sym p tom s of d iarrhea, bloating, fever,
ing in p atients you nger than age 50, are best resected u nless and m alaise and a p ositive hyd rogen breath test (91). Inter-
too nu m erou s or d iffu sely d istribu ted . Briskly bleed ing m ittent treatm ent w ith m etronid azole help s to re-establish
lesions also m u st be ad d ressed , preferably before extensive norm al flora and control sym p tom s. Micronu trient m alnu -
transfu sion is requ ired . trition can lead to osteop orosis, night blind ness, skin
rashes, calcu li form ation, anem ia, and im m u nopathy. Pre-
vention is effected by carefu l attention to vitam in, m ineral,
■ Ischemia and electrolyte rep lacem ent.
Intestinal ischemia in ad ults is generally the result of throm -
Therapeutic Intestinal Bypass for Weight Loss
boembolic d isease, small vessel d isease su ch as collagen-
vascular d isord ers, or a complication of previous operation. While intestinal su rgery generally is fou nd ed on im prov-
Diagnosis of intestinal ischemia can be d ifficult, and is ing the availability of nu trition, the u niqu e aim of a
based on symptoms and an examination consistent w ith bariatric intestinal bypass is to red uce nu tritional volu m e.
im pend ing peritonitis. The trad itional ad m onition of “pain In the United States, bariatric su rgery is enjoying renew ed
out of proportion to physical examination” is most easily p opu larity and is now the most comm on electively per-
appreciated w ith hind sight. Usefu l serology stud ies inclu d e form ed abd om inal op eration (92,93). Early com plications
the leukocyte count, lactate level, and bicarbonate level. of bariatric su rgery generally fall w ithin the sam e cate-
Thromboembolic d isease, chronic mesenteric ischemia, and gories as com p lications of p alliative byp ass, and anasto-
small vessel d isease are explored in a separate chapter. N on- m otic leak is ind ep end ently p red ictive of p ostop erative
vascular reasons for a low flow state, such as red uced car- m ortality (94). In p reviou s d ecad es, p rofou nd late com pli-
d iac output, usually compromise “w atershed ” areas of the cations of jeju noileal byp ass, esp ecially hep atic cirrhosis,
colon prior to affecting the small bow el. led to a m oratoriu m on the p roced u re (95–97). More
The most common etiology of postoperative intestinal recently, creation of a com m on intestinal channel 50 cm in
ischem ia is an incarcerated or strangu lated sm all bow el her- length has help ed to m itigate p rotein-calorie m alnu trition
nia. The d iagnosis is relatively straightforw ard am ong non- (97). Flow of bile and p ancreatic flu id throu gh the d efu nc-
obese patients w ith a ventral hernia. Ultrasound or CT scan tionalized lim b has red u ced bacterial overgrow th, and
can help to make the d iagnosis in the patient w hose exami- resu ltant d iarrhea, fever, and m alaise. Close p ostoperative
nation is obscu red by a thicker abd om inal w all. An incarcer- attention to vitam in su p p lem entation, p revention of elec-
ated intraperitoneal hernia can sometimes be ap preciated trolyte d istu rbances, and ad equ ate p rotein intake have
on CT scan, particularly if a clear transition point in the help ed to am eliorate sequ elae of m icronu trient d ep letion
small bow el lumen is seen. Mesenteric torsion is another and m alnu trition.
sou rce of intestinal ischemia. In ad ults, mesenteric torsion
may be a complication of the anastomotic alignment and is Palliative Bypass for Obstruction
easily avoid ed by p urp osefully orienting the m esenteric Intestinal bypass is an im portant alternative strategy w hen
ed ges d uring anastom osis or stom a form ation. resection is not feasible, for exam p le in the setting of short
Intraoperatively, questions regarding viability of bowel or bow el, p reviou s rad iation, m atted bow el or m esenteric
an anastomosis can be resolved by obtaining a Doppler sig- fibrosis, or w id ely d issem inated tu m or. The primary goal
nal at the antimesenteric border. Alternatively, intravenous of p alliative su rgical byp ass is relief of obstru ctive pain.
injection of 1 mg of fluorescein d ye followed by use of a Second ary goals are prevention of perforation and peri-
Wood’s lamp can delineate inadequately perfused bowel. In tonitis, and re-establishm ent of anatom ic continuity. The
addition, prudent use of a follow -up second look operation p atient’s preferences and a realistic assessm ent of the p rog-
will reveal ongoing ischemia or nonviable resection margins. nosis m u st be carefu lly consid ered p reop eratively. For
exam p le, a p atient w ith slow ly ad vancing obstru ction d u e Table 3 7 .1 0 Com p lica t ion s of ileost om y
to m esenteric fibrosis or longstand ing rad iation d am age for m a t ion a n d closu r e
potentially cou ld have m any rem aining years w ith a satis-
factory qu ality of life. Alternatively, a m oribu nd patient Early Complications Late Complications
w ho is not exp ected to recover m ay be best served by a less Both loop and Poor location Prolapse
invasive p roced u re for d ecom pression. The u nd erlying end ileostomies Poor orifice size Parastomal herniation
d isease p rocess affects tissue qu ality and p erfusion, w hich Ischemic necrosis Peristomal fistula formation
have a d irect im pact on intraop erative risks of unplanned Dehydration Bowel obstruction
enterotom y and anastomotic leakage. Late com plications Bowel obstruction Dermatitis
includ e m alnu trition, bacterial overgrow th, and renal and Parastomal abscess
biliary calcu li formation. Dermatitis
End ileostomy Retraction
Stenosis
■ Hypomotility Variceal bleeding
Intestinal m otility is m ed iated by an assortm ent of p ep - Loop ileostomy Erroneous closure of Closure-related:
tid es, horm ones, and extrinsic and intrinsic neu ral p ath- the proximal end Bowel obstruction
w ays. Transient hyp om otility second ary to p ostop erative Anastomotic leakage
ileu s, narcotic u se, bow el ed em a, or system ic inflam m a- Stricture formation
tion is best m anaged su p p ortively, w ith d ecom p ression,
flu id rep lacem ent, and rem oval of the offend ing sou rce if
p ossible. Longer-term hyp om otility can be iatrogenic as a tages of lap arotom y. H ow ever, p atients u nable to tolerate
resu lt of su rgically d isru p ted p athw ays, for exam p le p ost- long-term hyp eralim entation m ay benefit from consid era-
vagotom y or intestinal byp ass, or intrinsic as in the set- tion of sm all intestinal transp lantation.
ting of connective tissu e d isord ers, or visceral neu rop athy
or m yop athy.
■ Ileostomy complications
Chronic Intestinal Pseudoobstruction Ileostomies are usually created at the end of an operative
Intestinal pseudo-obstruction is manifested by abdominal case, after the abdomen has been closed and the senior sur-
distension, nausea, vomiting, and pain, and can be difficult to geon may have stepped back from the table. Although
distinguish clinically from mechanical obstruction. An incor- ileostomy formation seems simple enough, the technical
rect presumption of mechanical obstruction leading to opera- complication rate is not trivial. In 1952, Brooke mad e a major
tion can result in combined functional and mechanical contribution to red uction of ileostomy complications by pro-
obstruction, an even more challenging clinical situation. The posing immediate maturation (eversion) of the ileostomy
etiology of pseudo-obstruction is generally an und erlying end (100). How ever, in an actuarial analysis with a decade of
autoimmune connective tissue d isorder, such as systemic yearly follow-up, Leong and colleagues found that ileostomy
lupus erythematosus, sclerod erma, or amyloid osis. The complications still approached 76% among ulcerative colitis
prognosis is d irectly related to progress of the underlying dis- patients (101). Complications of end or loop ileostomy forma-
ease. Treatment is based on avoid ance of laparotomy, use of tion can be immed iately obvious or can continue to accrue
promotility agents, and supportive care (98). Anaerobic bac- over years (Table 37.10). Although much of the surgical
terial overgrowth can lead to steatorrhea and may require d ogma is now disputed , specific technical issues merit spe-
treatment with antibiotics. Chronic pain due to distension cial attention. Add itionally, volume replacement and treat-
may become severe enough to warrant creation of a venting ment w ith a bulking agent and anti-diarrheal medication can
enterostomy. Correcting d erangements of electrolytes, espe- prevent the numerous sequelae of dehydration.
cially magnesium, can also ameliorate symptoms.
Brooke Ileostomy
Visceral Myopathy/Neuropathy The most important initial steps in stoma creation, and pre-
Pseu d o-obstru ction p atients w ith no clear u nd erlying vention of complications, are appropriate siting, aligning the
connective tissu e abnorm ality are thou ght to have an abdominal wall tunnel through the rectus abdominus mus-
abnorm ality of the enteric sm ooth m u scle or (less fre- cle, and eversion of an adequate length of intestine (Fig. 37.5).
qu ently) intrinsic nervou s system (99). N u m erou s case The p rop osed area shou ld be flat, w ithin the patient’s
series rep ort su ch ill-d efined synd rom es, w hich tend to be view, and aw ay from scars, skin fold s, or bony prom i-
fam ilial, p rogressive, and to extend to other visceral or nences. Op tim ally this site is located throu gh the rectu s
even skeletal m u scle system s. Su p p ortive care inclu d es sheath, at 1/ 3 of the d istance betw een the u m bilicu s and
hyp eralim entation and m ed ication for vagu e bu t fre- the anterior su p erior iliac sp ine. In obese p atients, the
qu ently severe p ain. Prom otility agents have not p roven stom a site shou ld be shifted u p w ard for visu alization. An
u sefu l. Su rgical intervention is generally ineffective, leav- inap p rop riate site m ay lead to p oor ap p liance fit, leakage,
ing p atients vu lnerable to all of the risks bu t no ad van- and som etim es p rofou nd d erm atitis.
Ileostomy
site
Rectus
abdominis
muscle
Posterior
fascia
layer
HRFischer '04
Rectus abdominis muscle
Anterior fascia layer
B
FIGURE 37.5. Brooke ileostomy formation. A: Ileostomy site, B: Muscle splitting incision (continued )
A circu lar incision of 2 cm d iam eter is created sharp ly Vigorous clearing of m esentery from the ileal end can
and fat is d ivid ed to the anterior fascial sheath. The tract resu lt in ischem ia and is generally u nnecessary. Ad equ ate
shou ld be aligned by retracting the skin and fascia to the m obilization for eversion is cru cial at this step , especially if
m id line intraop eratively. A poorly aligned tract can cau se w eight gain is anticip ated . Inad equ ate m obilization can
obstru ction, ed em a, and ischem ia. A cru ciate incision is cre- lead to tension on the m esentery and ischem ia. Ad d ition-
ated in the anterior rectu s m u scle sheath u sing Bovie elec- ally, a poorly everted stoma may retract and stenose, result-
trocau tery. A m u scle splitting incision throu gh the rectu s ing in poor appliance fit, leakage, dermatitis, skin ulcerations,
m u scle shou ld p reserve the ep igastric vessels and exp ose and obstruction. Repair of a retracted, stenotic stoma fre-
the p osterior fascia for the next cru ciate incision. The tract quently requires laparotomy.
shou ld be blu ntly d ilated to about a 2 finger w id th, for Sm all bow el obstru ction, the m ost com m on com plica-
w ithd raw al of the m obilized term inal ileu m . tion of ileostom y form ation after skin breakd ow n, is m ost
HRFischer '04
C
FIGURE 37.5. (Continued) C: Eversion.
often cau sed by intra-abd om inal ad hesions. Other reasons notable d ifferences exist. Fu rtherm ore, closu re of the
for bow el obstru ction inclu d e fibrinous food bolus, p aras- ileostom y su m m ons a w hole d ifferent grou p of p otential
tom al herniation, intra-abd om inal torsion, and recu rrent com p lications.
Crohn’s d isease. Closing the lateral space or sew ing the Loop ileostom y form ation begins w ith the sam e p rinci-
mesentery to the abd om inal w all appears to have no p les as an end ileostomy (Fig. 37.6). Ascertainm ent of no
im pact on the long-term obstruction rate (101). tw ist in the bow el and m esentery is essential p rior to orien-
Parastom al herniation is essentially a ventral hernia- tation of the stom a lim bs. Placing the d istal limb in the
tion. The actu arial risk is about 16% and risk factors are d ep end ent p osition is stand ard techniqu e and can be help-
id entical to those of other incisional hernias: age, obesity, fu l for fu tu re op erative p lanning. In the event that the loop
pulm onary d isease, steroid d epend ence, and a history of ileostom y is to be converted to an end ileostom y, appropri-
hernias. Sym p tom relief can be provid ed by a cu stom ized ate orientation can help to p revent closing the w rong (prox-
truss. Ru bin and others reported a 76% recurrence rate im al) limb. Wrap p ing the intestinal loop in an ad hesion
w ith p rim ary fascia repair, 33% recu rrence rate w ith stom a barrier p rior to d elivery throu gh the fascia can greatly facil-
translocation, and an overall operative comp lication rate of itate fu tu re stom a closu re.
62% (102). Based on these d ata, the authors recom m end ed Loop ileostom ies are m ore p rone to p rolap se, w hich can
translocation as the initial repair strategy, follow ed by be qu ite d istressing to the p atient. Fortu nately, ad verse
mesh p lacem ent for recu rrent herniation. sequ elae are rare. Data are inconclu sive regard ing effec-
Peristomal fistu lae d evelop in abou t 7% of patients, tiveness of fixing the m esentery to p revent p rolap se.
most of w hom have Crohn’s d isease. Tacking su tu re Complications of ileostomy closure center on obstruction
throu gh the d erm is only, thus avoid ing a tract throu gh the and leakage. Because the distal limb may be substantially
epid erm is, and a w ell-fitted stom a appliance that lim its narrow ed , a sid e-to-sid e closure is best. In a rand omized
skin p ressu re m ay help to m inim ize this p roblem . trial of stapled versus sutured closure, H asegaw a and col-
Ileostom y p rovid es an ad d itional com m u nication leagues d etermined that a stapled closure was associated
betw een the p ortal and system ic venou s system s. Bleed - w ith 80% few er postoperative bow el obstructions (37).
ing varices can p otentially d evelop in cirrhotic p atients. H ow ever, hospital stay, read mission rates, and reoperative
Tem p orizing m easu res inclu d e oversew ing the bleed ing rates w ere the same.
site, cau terization or sclerosis, or even d isconnecting and
reanastom osing the m u cocu taneou s ju nction. Longer
term m anagem ent requ ires changing the p ortal flow or
■ J ejunostomy tube complications
cu ring the cirrhosis w ith a liver transp lant. Feeding jejunostomy tube placement has been an adjunct to a
variety of abdominal operations, but is associated with
Loop Ileostomy respective major complication and mortality rates of 4% to
A loop ileostom y is intend ed to be tem p orary. Althou gh 10% and 1.4% to 3.2% (103–106). The classic method for
the loop ileostom y is associated w ith m any of the sam e jejunostomy placement has been a sizeable tube through an
short-term com p lications as the end ileostom y, a few imbricated tract (Fig. 37.7) at least 30 cm beyond the ligament
HRFischer '04
B
E
F
FIGURE 37.6. Loop ileostomy formation. A: Delivery of intestine through the stoma incision, B: Proper orientation of the bowel: no bowel
torsion and distal limb inferior, C: Mechanical prevention of reduction prior to healing, D: Eversion of both limbs in a Brooke fashion, Eand
F: Final loop ileostomy appearance.
A B
FIGURE 37.7. Witzelling a jejunal feeding tube.

A: Placement of sutures longitudinally in the seromuscu-
lar layer, B: Imbrication of the tube, C: Prevention of tor-
C sion or kinking by fixing the bowel to the abdominal wall.
of Treitz, with sutures to the abdominal wall to prevent kink- 11. Ching SS, Mu ralikrishnan VP, Whiteley GS. Relap arotom y: a five-year
review of ind ications and ou tcom e. Int J Clin Pract 2003;57(4):333–337.
ing or torsion. 12. Ellozy SH , H arris MT, Bau er JJ, et al. Early p ostop erative sm all-bow el
A p rim ary ind ication for jejunostom y over gastrostomy obstru ction: a p rosp ective evalu ation in 242 consecu tive abd om inal
has been a p ercep tion of red u ced risk of aspiration. Fox and op erations. Dis Colon Rectum 2002;45(9):1214–1217.
13. Fraser SA, Shrier I, Miller G, et al. Im m ed iate p ostlap arotom y sm all
others retrosp ectively review ed gastrostom y and jeju nos- bow el obstruction: a 16-year retrospective analysis. Am Surg 2002;68(9):
tom y tu be p lacem ents and reported aspiration in 4 of 69 780–782.
patients w ith a gastrostom y tu be com pared w ith 2 of 86 14. Rou kem a JA, Carol EJ, Prins JG. The p revention of p u lm onary com -
plications after u p per abd om inal surgery in patients w ith noncom -
patients w ith a jeju nostom y tube (107). In contrast, Weltz prom ised pu lm onary statu s. Arch Surg 1988;123(1):30–34.
and others fou nd a su bstantially red uced rate of asp iration 15. H all JC, Tarala RA, Tap per J, et al. Prevention of resp iratory com p lica-
w ith feed ing by jeju nostom y tu be com p ared w ith feed ing tions after abd om inal su rgery: a rand om ised clinical trial. BMJ 1996;
312(7024):148–152; d iscu ssion 152–143.
by nasogastric tu be (105). 16. Gu im araes MM, El Dib R, Sm ith AF, et al. Incentive sp irom etry for
Leakage, torsion, and erosion w ith perforation of vis- prevention of p ostop erative pulm onary com plications in upp er
cera occu r infrequ ently bu t consistently. The trad itional abd om inal surgery. Cochrane Database Syst Rev 2009;(3):CD006058.
17. Eagle KA, Berger PB, Calkins H , et al. ACC/ AH A gu id eline u p d ate
jeju nostom y tu be m ay soon be ou tm od ed by new er enthu - for perioperative card iovascu lar evaluation for noncard iac su rgery–
siasm for p ercu taneou s, laparoscop ic, and need le catheter executive su m m ary: a rep ort of the Am erican College of Card iol-
placem ent. H ow ever, no clearly superior m ethod has been ogy/ Am erican H eart Association Task Force on Practice Gu id elines
(Com m ittee to Up d ate the 1996 Gu id elines on Periop erative Card io-
established thu s far. vascular Evalu ation for N oncard iac Su rgery). J Am Coll Cardiol 2002;
39(3):542–553.
■ SUMMARY
18. Potyk D, Raud askoski P. Preop erative card iac evalu ation for elective
noncard iac surgery. Arch Fam Med 1998;7(2):164–173.
19. Kern JW, Shoem aker WC. Meta-analysis of hem od ynam ic op tim iza-
In sum m ary, intestinal surgery is perform ed for an enor- tion in high-risk patients. Crit Care Med 2002;30(8):1686–1692.
mous variety of u nd erlying d iseases. Com plications that 20. Giner M, Laviano A, Megu id MM, et al. In 1995 a correlation betw een
m alnutrition and poor outcom e in critically ill patients still exists.
arise as a resu lt of technical errors can be associated Nutrition 1996;12(1):23–29.
broad ly w ith obstru ction or anastom otic leakage. Carefu l 21. Mid d leton MH , N azarenko G, N ivison-Sm ith I, et al. Prevalence of
postoperative attention to the patient w ill permit an earlier m alnu trition and 12-m onth incid ence of m ortality in tw o Syd ney
teaching hosp itals. Intern Med J 2001;31(8):455–461.
d iagnosis, w hich u su ally allow s m ore effective interven- 22. Post S, Betzler M, von Ditfurth B, et al. Risks of intestinal anastom oses
tion. Com p lications that arise as a result of errors of ju d g- in Crohn’s d isease. Ann Surg 1991;213(1):37–42.
ment m ay be m ore sp ecific to the und erlying d isease or 23. Wicke C, H allid ay B, Allen D, et al. Effects of steroid s and retinoid s on
w ou nd healing. Arch Surg 2000;135(11):1265–1270.
operation. Prevention of errors of ju d gm ent rests on a 24. Anstead GM. Steroid s, retinoid s, and w ou nd healing. Adv Wound Care
tim ely and thorou gh preoperative evalu ation, and a treat- 1998;11(6):277–285.
ment p lan based on specific features of the und erlying d is- 25. Slavin J, Unem ori E, H u nt TK, et al. Transform ing grow th factor beta
(TGF-beta) and d exam ethasone have d irect op p osing effects on colla-
ease. Op tim ization of the patient’s preoperative nu tritional gen m etabolism in low p assage hu m an d erm al fibroblasts in vitro.
statu s, ap p rop riate tim ing of surgery, and appreciation of Growth Factors 1994;11(3):205–213.
alternative treatm ent strategies are keys to the prevention 26. Marchal L, D’haens G, Van Aasche G, et al. The risk of p ost-op erative
com p lications associated w ith inflixim ab therapy for Crohn’s d isease:
and m anagem ent of com plications. a controlled cohort stu d y. Aliment Pharmacol Ther 2004;19:749–754.
27. Ap p au KA, Fazio VW, Shen B, et al. Use of inflixim ab w ithin 3 m onths
of ileocolonic resection is associated w ith ad verse p ostop erative ou t-
■ REFERENCES com es in Crohn’s p atients. J Gastrointest Surg 2008;12(10):1738–1744.
28. Kunitake H , H od in R, Shellito PC, et al. Periop erative treatm ent w ith
1. Ashley SW, Wells SA Jr. Tu m ors of the sm all intestine. Semin Oncol inflixim ab in patients w ith Crohn’s d isease and u lcerative colitis is not
1988;15(2):116–128. associated w ith an increased rate of p ostop erative com p lications. J
2. Fleming CR, Remington M. Intestinal Failure. In: Hill GL, ed . Nutrition Gastrointest Surg 2008;12(10):1730–1736; d iscu ssion 1736–1737.
and the Surgical Patient. New York: Churchill Livingstone; 1981:219–235. 29. H olm d ahl L, Risberg B, Beck DE, et al. Ad hesions: p athogenesis and
3. Periop erative total parenteral nu trition in su rgical p atients. The Veter- prevention-panel d iscussion and sum m ary. Eur J Surg Suppl 1997(577):
ans Affairs Total Parenteral N u trition Coop erative Stu d y Grou p. N 56–62.
Engl J Med 1991;325(8):525–532. 30. Thom pson J. Pathogenesis and p revention of ad hesion form ation. Dig
4. Bu zby GP. Overview of rand om ized clinical trials of total p arenteral Surg 1998;15(2):153–157.
nutrition for m alnourished su rgical p atients. World J Surg 1993;17(2): 31. Cu llen JJ, Kelly KA, Moir CR, et al. Su rgical m anagem ent of Meckel’s
173–177. d iverticu lum . An ep id em iologic, p op u lation-based stu d y. Ann Surg
5. N ightingale JM. The m ed ical m anagem ent of intestinal failu re: m eth- 1994;220(4):564–568; d iscu ssion 568–569.
od s to red u ce the severity. Proc Nutr Soc 2003;62(3):703–710. 32. Fisher KS, Ross DS. Guid elines for therap eu tic d ecision in incid ental
6. Ziegler TR, Evans ME, Fernand ez-Estivariz C, et al. Trop hic and cyto- app end ectom y. Surg Gynecol Obstet 1990;171(1):95–98.
protective nutrition for intestinal ad ap tation, m u cosal rep air, and bar- 33. Snyd er TE, Seland ers JR, Strom PR, et al. Incid ental ap p end ectom y—
rier fu nction. Annu Rev Nutr 2003;23:229–261. yes or no? A retrosp ective case stu d y and review of the literatu re
7. Tera H , Aberg C. Relap arotom y. A ten-year series. Acta Chir Scand Safety of incid ental ap pend ectom y. Infect Dis Obstet Gynecol 1998;6(1):
1975;141(7):637–644. 30–37.
8. Zer M, Du x S, Dintsm an M. The tim ing of relap arotom y and its influ- 34. Strom PR, Turkleson ML, Stone H H . Safety of incid ental ap p end ec-
ence on p rognosis. A 10 year su rvey. Am J Surg 1980;139(3):338–343. tom y. Am J Surg 1983;145(6):819–822.
9. van Goor H , H u lsebos RG, Bleichrod t RP. Com p lications of planned 35. Warren JL, Penberthy LT, Ad d iss DG, et al. Ap p end ectom y incid ental
relap arotom y in p atients w ith severe general p eritonitis. Eur J Surg to cholecystectom y among eld erly Med icare beneficiaries. Surg Gynecol
1997;163(1):61–66. Obstet 1993;177(3):288–294.
10. Golu b R, Golu b RW, Cantu R Jr, et al. A m u ltivariate analysis of factors 36. Brund age SI, Ju rkovich GJ, Grossm an DC, et al. Stap led versu s
contribu ting to leakage of intestinal anastom oses. J Am Coll Surg 1997; su tu red gastrointestinal anastom oses in the trau m a p atient. J Trauma
184(4):364–372. 1999;47(3):500–507; d iscu ssion 507–508.
37. H asegaw a H , Rad ley S, Morton DG, et al. Stap led versu s su tu red clo- 63. Sudan DL, Kaufman SS, Shaw BW Jr, et al. Isolated intestinal transplan-
sure of loop ileostom y: a rand om ized controlled trial. Ann Surg 2000; tation for intestinal failure. Am J Gastroenterol 2000;95(6):1506–1515.
231(2):202–204. 64. Abu -Elm agd K, Reyes J, Bond G, et al. Clinical intestinal transp lanta-
38. H ym an N , Manchester TL, Osler T, et al. Anastom otic leaks after tion: a d ecad e of exp erience at a single center. Ann Surg 2001;234(3):
intestinal anastom osis: it’s later than you think. Ann Surg 2007;245(2): 404–416; d iscussion 416–407.
254–258. 65. Abu -Elm agd K, Bond G. Gu t failu re and abd om inal visceral trans-
39. Zieren H U, Mu ller JM, Pichlm aier H . Prosp ective rand om ized stu d y plantation. Proc Nutr Soc 2003;62(3):727–737.
of one- or tw o-layer anastom osis follow ing oesop hageal resection and 66. Bernell O, Lap id u s A, H ellers G. Risk factors for su rgery and recu r-
cervical oesop hagogastrostom y. Br J Surg 1993;80(5):608–611. rence in 907 p atients w ith p rim ary ileocaecal Crohn’s d isease. Br J
40. Ku m ar S, Wong PF, Leap er DJ. Intra-p eritoneal p rop hylactic agents Surg 2000;87(12):1697–1701.
for preventing ad hesions and ad hesive intestinal obstru ction after 67. Yam am oto T, Allan RN , Keighley MR. Risk factors for intra-abd om i-
non-gynaecological abd om inal su rgery. Cochrane Database Syst Rev nal sepsis after su rgery in Crohn’s d isease. Dis Colon Rectum 2000;
2009;(1):CD005080. 43(8):1141–1145.
41. Vrijland WW, Tseng LN , Eijkm an H J, et al. Few er intrap eritoneal 68. Bruew er M, Utech M, Rijcken EJ, et al. Preoperative steroid administra-
ad hesions w ith use of hyalu ronic acid -carboxym ethylcellu lose m em - tion: effect on m orbid ity am ong patients und ergoing intestinal bow el
brane: a rand om ized clinical trial. Ann Surg 2002;235(2):193–199. resection for Crohn’s d isease. World J Surg 2003;27(12):1306–1310.
42. Becker JM, Dayton MT, Fazio VW, et al. Prevention of postop erative 69. Tay GS, Binion DG, Eastw ood D, et al. Mu ltivariate analysis su ggests
abd om inal ad hesions by a sod iu m hyalu ronate-based bioresorbable im proved perioperative outcom e in Crohn’s d isease p atients receiv-
m em brane: a p rosp ective, rand om ized , d ou ble-blind m u lticenter ing im m u nom od u lator therapy after segm ental resection and / or
stu d y. J Am Coll Surg 1996;183(4):297–306. strictu rep lasty. Surgery 2003;134(4):565–572; d iscu ssion 572–563.
43. Beck DE, Cohen Z, Fleshm an JW, et al. A p rosp ective, rand om ized , 70. Borley N R, Mortensen N J, Jew ell DP. Preventing p ostop erative recu r-
m u lticenter, controlled stu d y of the safety of Sep rafilm ad hesion bar- rence of Crohn’s d isease. Br J Surg 1997;84(11):1493–1502.
rier in abd om inop elvic su rgery of the intestine. Dis Colon Rectum 71. Lichtenstein GR. Treatm ent of fistu lizing Crohn’s d isease. Gastroen-
2003;46(10):1310–1319. terology 2000;119(4):1132–1147.
44. Rem zi FH , Oncel M, Chu rch JM, et al. An u nu su al com p lication after 72. Broe PJ, Bayless TM, Cam eron JL. Crohn’s d isease: are enteroenteral
hyaluronate-based bioresorbable m em brane (Seprafilm ) application. fistu las an ind ication for su rgery? Surgery 1982;91(3):249–253.
Am Surg 2003;69(4):356–357. 73. Wu llstein C, Gross E. Lap aroscop ic com p ared w ith conventional
45. Klingler PJ, Floch N R, Seelig MH , et al. Sep rafilm -ind u ced p eritoneal treatm ent of acu te ad hesive sm all bow el obstru ction. Br J Surg 2003;
inflam m ation: a p reviou sly u nknow n com p lication. Report of a case. 90(9):1147–1151.
Dis Colon Rectum 1999;42(12):1639–1643. 74. Yam am oto T, Keighley MR. Long-term resu lts of strictu rep lasty for
46. David M, Sarani B, Moid F, et al. Parad oxical inflam m atory reaction to ileocolonic anastom otic recu rrence in Crohn’s d isease. J Gastrointest
Seprafilm : case rep ort and review of the literatu re. South Med J Surg 1999;3(5):555–560.
2005;98(10):1039–1041. 75. d e Jong E, van Du llem en H M, Slors JF, et al. Correlation betw een early
47. Carroll J, Alavi K. Pathogenesis and m anagem ent of postop erative recu rrence and reoperation after ileocolonic resection in Crohn’s d is-
ileu s. Clin Colon Rectal Surg 2009;22(1):47–50. ease: a p rosp ective stu d y. J Am Coll Surg 1996;182(6):503–508.
48. Seror D, Feigin E, Szold A, et al. H ow conservatively can p ostop era- 76. Tytgat GN , Mu ld er CJ, Bru m m elkam p WH . End oscop ic lesions in
tive sm all bow el obstru ction be treated ? Am J Surg 1993;165(1): Crohn’s d isease early after ileocecal resection. Endoscopy 1988;20(5):
121–125; d iscussion 125–126. 260–262.
49. Shih SC, Jeng KS, Lin SC, et al. Ad hesive sm all bow el obstru ction: 77. William s JG, Wong WD, Rothenberger DA, et al. Recu rrence of
how long can patients tolerate conservative treatm ent? World J Gas- Crohn’s d isease after resection. Br J Surg 1991;78(1):10–19.
troenterol 2003;9(3):603–605. 78. Wobbes T, Verschu eren RC, Lu bbers EJ, et al. Su rgical asp ects of rad i-
50. Fevang BT, Jensen D, Svanes K, et al. Early op eration or conservative ation enteritis of the sm all bow el. Dis Colon Rectum 1984;27(2):89–92.
m anagem ent of p atients w ith sm all bow el obstruction? Eur J Surg 79. Sw an RW. Stagnant loop synd rom e resu lting from sm all-bow el irrad i-
2002;168(8–9):475–481. ation injury and intestinal by-p ass. Gynecol Oncol 1974;2(4):441–445.
51. Thom pson JS. Surgical consid erations in the short bow el synd rom e. 80. Dietz DW, Rem zi FH , Fazio VW. Strictu rep lasty for obstru cting sm all-
Surg Gynecol Obstet 1993;176(1):89–101. bow el lesions in d iffu se rad iation enteritis–su ccessfu l ou tcom e in five
52. Thom pson JS. Ed gar J. Poth Mem orial Lectu re. Su rgical aspects of the p atients. Dis Colon Rectum 2001;44(12):1772–1777.
short-bow el synd rom e. Am J Surg 1995;170(6):532–536. 81. Agha FP. Intussu sception in ad u lts. AJR Am J Roentgenol 1986;146(3):
53. N ightingale JM, Lennard -Jones JE, Gertner DJ, et al. Colonic p reserva- 527–531.
tion red uces need for p arenteral therap y, increases incid ence of renal 82. Lvoff N , Breim an RS, Coakley FV, et al. Distingu ishing featu res of self-
stones, but d oes not change high p revalence of gall stones in p atients lim iting ad ult sm all-bow el intu ssu scep tion id entified at CT. Radiology
w ith a short bow el. Gut 1992;33(11):1493–1497. 2003;227(1):68–72.
54. Tang SJ, N ieto JM, Jensen DM, et al. The novel u se of an intravenou s 83. N aef M, Bu hlm ann M, Baer H U. Small bow el tu m ors: d iagnosis, ther-
proton p u m p inhibitor in a p atient w ith short bow el synd rom e. J Clin apy and prognostic factors. Langenbecks Arch Surg 1999;384(2):176–180.
Gastroenterol 2002;34(1):62–63. 84. N etterville RE, H ard y JD, Martin RS Jr. Sm all bow el hem orrhage. Ann
55. Scolap io JS, Cam illeri M, Flem ing CR, et al. Effect of grow th horm one, Surg 1968;167(6):949–957.
glu tam ine, and d iet on ad ap tation in short-bow el synd rom e: a ran- 85. Rabe FE, Becker GJ, Besozzi MJ, et al. Efficacy stu d y of the sm all-
d om ized , controlled stu d y. Gastroenterology 1997;113(4):1074–1081. bow el exam ination. Radiology 1981;140(1):47–50.
56. Scolap io JS. Effect of grow th horm one and glu tam ine on the short 86. Lew is BS. Sm all intestinal bleed ing. Gastroenterol Clin North Am 2000;
bow el: five years later. Gut 2000;47(2):164. 29(1):67–95, vi.
57. Szku d larek J, Jep p esen PB, Mortensen PB. Effect of high d ose grow th 87. Mata A, Bord as JM, Feu F, et al. Wireless cap su le end oscop y in
horm one w ith glu tam ine and no change in d iet on intestinal absorp- patients w ith obscure gastrointestinal bleed ing: a com p arative stud y
tion in short bow el p atients: a rand om ised , d ou ble blind , crossover, w ith pu sh enteroscop y. Aliment Pharmacol Ther 2004;20(2):189–194.
placebo controlled stu d y. Gut 2000;47(2):199–205. 88. Mylonaki M, Fritscher-Ravens A, Swain P. Wireless capsule endoscopy:
58. H allgren T, Fasth S, Delbro DS, et al. Lop eram id e im p roves anal a com p arison w ith push enteroscop y in patients w ith gastroscopy
sp hincter fu nction and continence after restorative p roctocolectom y. and colonoscop y negative gastrointestinal bleed ing. Gut 2003;52(8):
Dig Dis Sci 1994;39(12):2612–2618. 1122–1126.
59. Bianchi A. Intestinal loop lengthening—a techniqu e for increasing 89. Zu ckerm an GR, Prakash C, Askin MP, et al. AGA technical review on
sm all intestinal length. J Pediatr Surg 1980;15(2):145–151. the evalu ation and m anagem ent of occult and obscu re gastrointesti-
60. Bianchi A. Experience w ith longitu d inal intestinal lengthening and nal bleed ing. Gastroenterology 2000;118(1):201–221.
tailoring. Eur J Pediatr Surg 1999;9(4):256–259. 90. Lewis B, Goldfarb N. Review article: The advent of capsule endoscopy–a
61. Thom pson JS. Strategies for p reserving intestinal length in the short- not-so-fu tu ristic app roach to obscu re gastrointestinal bleed ing. Ali-
bow el synd rom e. Dis Colon Rectum 1987;30(3):208–213. ment Pharmacol Ther 2003;17(9):1085–1096.
62. Fishbein TM, Matsumoto CS. Intestinal replacement therapy: tim ing 91. Riord an SM, McIver CJ, Walker BM, et al. The lactu lose breath hyd ro-
and indications for referral of patients to an intestinal rehabilitation and gen test and sm all intestinal bacterial overgrow th. Am J Gastroenterol
transplant program . Gastroenterology 2006;130(2 Suppl 1):S147–S151. 1996;91(9):1795–1803.
92. Livingston EH . Proced u re incid ence and in-hosp ital com p lication 102. Ru bin MS, Schoetz DJ Jr, Matthew s JB. Parastom al hernia. Is stom a
rates of bariatric surgery in the United States. Am J Surg 2004;188(2): relocation su p erior to fascial rep air? Arch Surg 1994;129(4):413–418;
105–110. d iscu ssion 418–419.
93. Pop e GD, Birkm eyer JD, Finlayson SR. N ational trend s in u tilization 103. Holmes JH IV, Brund age SI, Yuen P, et al. Complications of surgical
and in-hospital ou tcom es of bariatric su rgery. J Gastrointest Surg feed ing jejunostomy in trauma patients. J Trauma 1999;47(6):1009–1012.
2002;6(6):855–860; d iscu ssion 861. 104. Sonaw ane RN , Thom bare MM, Ku m ar A, et al. Technical com p lica-
94. Fernand ez AZ Jr, Dem aria EJ, Tichansky DS, et al. Mu ltivariate analy- tions of feed ing jeju nostom y: a critical analysis. Trop Gastroenterol
sis of risk factors for d eath follow ing gastric bypass for treatm ent of 1997;18(3):127–128.
m orbid obesity. Ann Surg 2004;239(5):698–702; d iscu ssion 702–693. 105. Weltz CR, Morris JB, Mu llen JL. Su rgical jeju nostom y in asp iration
95. Backm an L, H allberg D. Som e som atic com p lications after sm all intes- risk patients. Ann Surg 1992;215(2):140–145.
tinal byp ass operations for obesity. Possible factors of significance in 106. Sim on T, Fink AS. Recent exp erience w ith p ercu taneou s end oscop ic
the incid ence. Acta Chir Scand 1975;141(8):790–800. gastrostom y/ jeju nostom y (PEG/ J) for enteral nu trition. Surg Endosc
96. Dean P, Joshi S, Kam inski DL. Long-term ou tcom e of reversal of sm all 2000;14(5):436–438.
intestinal bypass operations. Am J Surg 1990;159(1):118–123; d iscu s- 107. Fox KA, Mu larski RA, Sarfati MR, et al. Asp iration p neu m onia fol-
sion 123–114. lowing surgically placed feeding tubes. Am J Surg 1995;170(6): 564–566;
97. Sugerm an H J, Kellu m JM, DeMaria EJ. Conversion of Proxim al to Dis- d iscussion 566–567.
tal Gastric Byp ass for Failed Gastric Byp ass for Su p erobesity. J Gas- 108. Joelsson I, Raf L. Late injuries of the sm all intestine follow ing rad io-
trointest Surg 1997;1(6):517–525. therapy for u terine carcinom a. Acta Chir Scand 1973;139(2): 194–200.
98. H irsh EH , Brand enbu rg D, H ersh T, et al. Chronic intestinal pseud o- 109. Sw an RW, Fow ler WC Jr, Boronow RC. Su rgical m anagem ent of rad i-
obstru ction. J Clin Gastroenterol 1981;3(3):247–254. ation inju ry to the sm all intestine. Surg Gynecol Obstet 1976;142(3):
99. Mann SD, Debinski H S, Kam m MA. Clinical characteristics of chronic 325–327.
id iopathic intestinal p seu d o-obstru ction in ad u lts. Gut 1997;41(5): 110. Schmitt EH III, Symm onds RE. Surgical treatment of radiation induced
675–681. injuries of the intestine. Surg Gynecol Obstet 1981;153(6):896–900.
100. Brooke BN . The m anagem ent of an ileostom y, inclu d ing its com plica- 111. Lillem oe KD, Brigham RA, H arm on JW, et al. Su rgical m anagem ent of
tions. Lancet 1952;2(3):102–104. sm all-bow el rad iation enteritis. Arch Surg 1983;118(8):905–907.
101. Leong AP, Londono-Schimmer EE, Phillips RK. Life-table analysis of 112. Galland RB, Spencer J. N atu ral history and su rgical m anagem ent of
stomal complications follow ing ileostomy. Br J Surg 1994;81(5):727–729. rad iation enteritis. Br J Surg 1987;74(8):742–747.
CHAPTER
38
Complications of Appendectomy
and Colon and Rectal Surgery
Emily Finlayson
Ap p end icitis is the m ost com m on cau se of acu te p ain in peritonitis may occur. Generalized peritonitis is more com-
the abd om en requ iring su rgical intervention and m u st be mon in children, w ho possess a less generous omentum.
consid ered in any p atient com p laining of abd om inal p ain. Although localized peritonitis may occur in patients w ith a
The lifetim e incid ence of acu te ap p end icitis is 6.7% to 20%, periappend iceal abscess d ue to perforated append icitis, gen-
w ith the lifetim e incid ence of ap p end ectom y of 12% for eralized peritonitis may also occur if the abscess loses its
m en and 23% for w om en (1). The p resentation of ap p en- containment. Associated sepsis is due to mixed colonic flora,
d icitis is often confu sing and m ay cau se d elayed d iagno- includ ing anaerobic Bacteroides, aerobic Escherichia coli, and
sis, esp ecially in p atient p op u lations in w hich other streptococci. Antimicrobial treatment should be targeted to
changes in p hysiology, su ch as p regnancy or extrem es in these organisms.
age, m ay exist. The accep ted p athop hysiology of ap p en- When a patient presents several days after the onset of
d icitis contribu tes d irectly to p resentation, d iagnosis, and symptoms, a contained perforation w ith abscess is common.
com p lications. In this setting, operative d rainage with or without appen-
The classic history of pain—first d iffuse, then localizing d ectomy is associated w ith a high morbidity of 18% to 50%
to the right low er qu ad rant of the abd om en—associated (4,5). Radiologic imaging in the form of ultrasound or CT
w ith fever is obtained in only half of patients (2). Associ- scan can confirm the diagnosis and facilitates nonoperative
ated sym p tom s of anorexia and vom iting m ay be absent. management. Small ( 3 cm) abscesses respond to bow el rest
Therefore, clinical suspicion m u st be m aintained in and intravenous antibiotics, w hereas larger abscesses
patients still p ossessing an append ix w hen history or p hys- require percutaneous drainage. With this approach, an ini-
ical exam ination is atyp ical. Diagnosis can be particu larly tial failure rate of 12% necessitates urgent appendectomy,
d ifficu lt in sm all child ren, w ho are u nable to give a history, w hich has a complication rate of 12% (6). Because recurrent
and in the eld erly. Ultrasound or com puted tom ograp hy append icitis occurs w ith an incid ence of 8% to 14% follow -
(CT) can often clarify an atypical clinical picture. The rad io- ing resolution of the acute episod e, the practice of routine
logic literature reports d iagnostic sensitivities as high as interval append ectomy after the resolution of symptoms is
92% (3) w hen these stu d ies are used as ad ju ncts to history controversial (7). Although the risk of recurrence is low,
and p hysical exam ination. Rad iographic stud ies are help - ad d itional pathology may be id entified in the append ix or
fu l in confirm ing the d iagnosis of append icitis, and they cecum. A barium enema or colonoscopy can be performed to
d ecrease the incid ence of negative append ectom y. In ad d i- d etermine w hether other pathology exists.
tion, abd om inal im aging can id entify patients w ith p erfo-
rated ap p end icitis w ith a w ell-d efined p eriap p end iceal
abscess collection w ho w ould benefit from percu taneou s
d rainage follow ed by interval ap p end ectom y. The m ost com m on postoperative com plication of appen-
d icitis is w ou nd infection. Sim ilar to m u ch of the m orbid ity
of ap p end icitis, this com p lication’s incid ence is correlated
■ COMPLICATIONS AT PRESENTATION
w ith the p athology’s severity. In p atients w ith nonperfo-
Peritonitis is a common complication of append icitis, and it rated ap p end icitis, the incid ence of w ou nd infection is
implies that the d isease process has progressed , w ith associ- 10%; w ou nd infection increases w ith p erforated appen-
ated ischemia, mucosal ulceration, transmural necrosis, and d icitis to 15% to 20% and is highest w ith d iffu se peritonitis
leakage of bacteria and fecal material. Peritonitis may be (35%) (8). Wou nd infection is significantly less com m on
localized if the surround ing organs—the sm all bow el, colon, after ap p end ectomy p erform ed lap aroscop ically (9). The
omentum, or colonic epiploicae—contain the perforation. In offend ing organism s are colonic bacteria, especially Bac-
the absence of this protective host response, generalized teroides fragilis and E. coli.
If the patient d oes not resolve fever postoperatively and
Emily Finlayson: Dep artm ent of Su rgery, University of the w ou nd is exclu d ed as a sou rce of infection, an intraab-
California, San Francisco d om inal abscess shou ld be su sp ected . The m ost com m on
483
locations for abscesses are the iliac fossa, the pericecal area, d ep end s on size and histologic featu res. Right hem icolec-
and the p elvis. Both CT scan and ultrasound are u sefu l tomy is ind icated for tumors 2 cm, for those w ith evid ence
im aging techniqu es for d iagnosis, and both provid e a of lym p hovascu lar invasion, and for tu m ors of interm ed i-
guid e for d rainage. ate size in you nger p atients.
Continu ed feculent d rainage raises concern for a fecal Mu cocele of the ap p end ix is cau sed by either benign or
fistu la. Usu ally, a fecal fistu la is the resu lt of a necrotic m alignant d isease. In the benign form , m u cu s accu m ulates
append iceal stu m p or cecu m . A fecal fistula m ay also su g- d istal to an obstru ction of the ap p end iceal lu m en. The
gest a new d iagnosis of Crohn d isease. Im aging stu d ies malignant form is d ue to mucous cystad enocarcinoma, a
shou ld be u sed to ensu re that d rainage is ad equ ate and to tumor that usually d oes not metastasize but that prod uces
d eterm ine the sou rce of the fistu la. A low -outpu t fistu la mucus. If the malignant form ruptures, intraperitoneal
should close in the absence of d istal obstru ction, neop lasia, tumor causes pseud om yxoma peritonei. The large amounts
rad iation, or inflam m atory bow el d isease. of gelatinous material may cause mechanical obstruction,
w ith d ebulking and chemotherapy necessary for sym pto-
■ Special considerations m atic relief. For the benign form of d isease, ap p end ectom y
is su fficient. For the m alignant form , right hem icolectom y
Pregnancy is recom m end ed .
The gravid u teru s alters both the p resentation and the m or- Ad enocarcinom a of the append ix is rare and presents
bid ity of ap p end icitis. The increasing size of the uteru s d is- either as ap p end icitis or as ru p tu red , d issem inated d isease.
places the ap p end ix out of its usual pelvic position, into the Right hem icolectom y is recom m end ed to rem ove the asso-
mid and u p p er abd om en. N ausea and vom iting, w hich ciated lym ph nod es.
often accom p any early p regnancy, further confu se the p ic-
tu re. Ultrasou nd is key to d eterm ine the viability of the
pregnancy and to d iagnose append icitis. CT scan and m ag- ■ COLORECTAL SURGERY
netic resonance im aging (MRI) have been used , bu t fear of Surgical proced ures for d iseases of the colon and rectum
rad iation to a fetu s and u nknow n effects of MRI have m ad e are am ong the m ost com mon p roced u res p erform ed . Brief
these m od alities less p op u lar. sum m aries of d isease processes for w hich colorectal resec-
Since m iscarriage is associated w ith append icitis, early tion is necessary follow, w ith d iscu ssion of the com plica-
d iagnosis and therap y are critical. The incid ence of m iscar- tions that are com m on to all the d isease processes for w hich
riage is 10% in the absence of perforation, bu t it increases to colon or rectal resection is requ ired . Uniqu e com plications
30% in the p resence of p erforation (10). Concerns abou t the of the ileal p ou ch–anal anastom osis w ill then be ou tlined ,
laparoscop ic ap p roach, includ ing d ecreased uterine blood follow ed by com p lications d istinct to p roced u res in w hich
flow, fetal hyp otension and hypoxia, and acid osis d u e to an anastom osis is not created —that is, to p erm anent stom a
CO 2, d o not seem to be m ajor issu es; how ever, cu rrent form ation.
inform ation is retrospective in nature. In ad d ition, the com -
plications that have been reported w ith lap aroscop y have
been associated also w ith append icitis, general anesthesia, ■ INDICATIONS FOR SURGERY
and the op en su rgical proced u re (11).
■ Diverticular disease
Elderly Althou gh initial rep orts early in the 20th centu ry d escribed
Althou gh p eop le old er than 70 years constitu te only 5% to an incid ence of d iverticu losis in the 5% to 10% range (16),
10% of p atients w ith app end icitis, m orbid ity and m ortality cu rrent estim ates d escribe an occu rrence as high as 65% in
in this age grou p is high. These patients m ay have signifi- those old er than 85 years. Althou gh d iverticu losis is qu ite
cant com orbid ities, w hich, w ith atypical and d elayed p recom m on, only 10% to 30% of p atients w ill becom e sym pto-
sentations, contribute to an incid ence of perforation as high m atic (17) from inflam m ation, obstru ction, or bleed ing.
as 70% (12,13). Often, elderly patients with append icitis are Mu ltip le classification schem es have been d evelop ed to
incorrectly diagnosed with d iverticulitis and bow el obstruc- categorize acute inflammatory episod es. The most quoted is
tion, and op erative intervention m ay be d elayed (14). the H inchey classification (18). In the absence of generalized
Recent ad vances in im aging and laparoscopy have facili- p eritonitis, stage I and II presentations may be treated w ith
tated the d iagnosis and treatment of append icitis. H ow ever, antimicrobial agents and percutaneous d rainage as need ed ,
ad option of these mod alities has not yet influ enced results allow ing a d elayed , elective proced u re. H ow ever, the more
in the eld erly, w ith consistently elevated rates of perforation severe presentations of pu ru lent peritonitis (stage III) or
and morbidity (15). fecal p eritonitis (stage IV) m and ate em ergent resection of
the perforated sigm oid colon.
Tumors of the Appendix Low er gastrointestinal tract hem orrhage d u e to d iver-
Carcinoid tum or is the m ost com m on neoplasm of the ticu la w ill often cease sp ontaneou sly (19) and p resents one
append ix. Many carcinoid tum ors are d iscovered incid en- of the m ost d ifficu lt d iagnostic d ilem mas w ithin su rgery.
tally and often only as a histopathologic find ing. Therap y Angiod ysp lasia is more com m on on the right sid e of the
Chapter 38 • Complications of Appendectomy and Colon and Rectal Surgery 485
colon. Exclu sion of both an anorectal source of bleed ing w ith ileostom y, ileal p ou ch reconstru ction, or ileorectal
and an u p p er gastrointestinal cau se is necessary. Once anastom osis.
these sou rces have been exclu d ed , colonoscopy is the next
step . The op p ortunity for therapeu tic em bolization and Rectal Prolapse
localization exists w ith angiography. Prior to op erative Rectal p rolap se is an intu ssu scep tion of the fu ll thickness of
resection, localization is requ ired to ensu re a su ccessfu l the rectal w all throu gh the anal sp hincter. The other d isease
segm ental resection. p rocess that m ay be confu sed w ith rectal prolapse is rectal
m u cosal or hem orrhoid al p rolap se. In contrast to rectal
Ulcerative Colitis p rolap se, w here m u cosal fold s are circu lar, in hem or-
In the United States, this enigm atic d isease has an inci- rhoid al p rolap se, these fold s are orientated rad ially.
d ence of 5 to 15 p er 100,000 (20). The causative agent or Since p athop hysiology is p oorly u nd erstood , a variety
provoking elem ents for ulcerative colitis have not been of p roced u res are available for treating this entity. The m ost
id entified . Fam ilial tend encies d o exist. Ind ications for su r- p opu lar perineal approaches includ e those of Altem eier
gery inclu d e toxic m egacolon, perforation, bleed ing, and Delorm e, w hereas the choices for the abd om inal
grow th retard ation in child ren and , m ost com m only, ap p roaches inclu d e su tu red rectop exy, the Rip stein proce-
intractability to med ical therapy. One of the m ost seriou s d u re, anterior resection, abd om inal rectop exy, and sigm oid
com p lications of extensive or long-stand ing u lcerative resection, w ith lap aroscop ic op tions available for the
colitis is the d evelopm ent of colon or rectal carcinom a. abd om inal ap p roaches. Variations in recu rrence rates have
Early in the d isease process, the risk is 5%. With an been reported and m ay influence the choice of p roced ure.
increased d u ration of the d isease, the risk rises to 50% and
75%, resp ectively, after 30 and 40 years (21). Ischemic Colitis
Total p roctocolectom y w ith ileostom y is the stand ard The m ost com m on form of gastrointestinal ischem ia is
against w hich other op erations are m easured . The ileal ischemic colitis. The etiology is believed to be “w atershed ”
pou ch–anal anastom osis w as first d escribed in 1978 and areas of colonic blood su pply, inclu d ing the splenic flexure
has becom e the m ost popular curative reconstru ction. Usu - and the rectosigmoid . Treatment of ischemic colitis d epend s
ally created w ith a d iverting loop ileostom y, w hich may on the d egree of injury. With early d iagnosis of mild cases,
itself becom e the sou rce of com p lication, this p roced u re bow el rest w ith ad junctive intravenous antibiotics is benefi-
rem oves the d iseased tissue and allow s for m aintenance of cial. Optimization of blood flow to prevent further ischemia
continence. Total abd om inal colectom y w ith ileostom y and is mand atory. More severe cases, w ith peritonitis, perfora-
the H artm ann p roced u re or m u cu s fistu la m ay be p er- tion, sepsis, clinical d eterioration d espite m ed ical therapy,
form ed in the em ergent setting. or gangrene, require colectomy.
Crohn Disease Colorectal Carcinoma

In the United States, the incid ence of Crohn d isease is Recent cancer statistics show that colorectal cancer rem ains
approximately 5 per 100,000. The etiology is unknown. the third m ost com m on cau se of cancer d eath in the United
Crohn d isease is not limited to the colorectum and may States (23). In 2003, ap p roxim ately 147,000 new cases of col-
involve the gastrointestinal tract anywhere from mouth to orectal cancer w ere d iagnosed , w ith ap p roxim ately 55,100
anus. Ileocolic disease is the most common, but Crohn colitis d eaths. In N orth Am erica, there is a 6% lifetim e risk. Since
may be the only manifestation in up to 45% of patients (22). surgical resection is the only cu rative treatm ent for colon
Disease limited to the anorectum occurs in 5% of patients. cancer, colectom y, inclu d ing the tu m or, ad equ ate margins,
For intractable Crohn colitis, proctocolectom y w ith segm ented blood su p p ly, and d raining lym p h nod es, is the
ileostom y is the stand ard of treatm ent. For lim ited d isease, m ainstay of treatm ent.
segm ental colectom y or total abd om inal colectom y is p os-
sible, p rovid ed that grossly norm al bow el is available for
anastom osis. ■ POSTOPERATIVE COMPLICATIONS
OF COLORECTAL SURGERY
Familial Adenomatous Polyposis
Fam ilial ad enom atous polyposis is an autosom al d om inant
■ Ileus
d isease characterized by the d evelop m ent of m ultip le Postoperative ileus is a form of temporary bow el motor d ys-
polyp s in the colon. The d isease is cau sed by a d eletion function that follows operative procedures in the abdomen.
mu tation in chrom osom e 5q21 at the ad enom atou s p olyp o- This reflex is caused by excitation of the splanchnic sympa-
sis coli gene, w hich norm ally acts as a tu m or su p p ressor. thetic nerves that occurs during manipulation of the bow el,
Relatively comm on, w ith an incid ence of 1 in 7,000 to but it may also be associated w ith surgery or trauma to other
10,000, sp ontaneou s m u tations d o occu r and represent 15% organs. The stom ach recovers from this state w ithin several
to 20% of p atients. Since transform ation to m alignancy is hou rs, w hereas the sm all bow el requ ires 1 to 2 d ays and the
ensu red by the age of 40 years, total p roctocolectom y is colon 2 to 3 d ays. Recovery that inclu d es coord inated
recom m end ed . Total proctocolectom y has been com bined m otor fu nction m ay requ ire u p to 5 d ays. Althou gh the
auscu ltation of bow el sound s or resumption of appetite The risk of op erative m ortality increases 10-fold w ith an
have been used to herald the resolution of ileus, the passage anastom otic leak. Am ong the m ost significant risk factors
of flatus is the only true ind icator that colonic ileus has for anastom otic leak is the location of the anastom osis. In
resolved. An ileus lasting for longer periods may be associ- large series, intraabd ominal leak rates range from 1% to 5%
ated with peritonitis or hematoma. and p elvic leak rates range from 5% to 30%. The closer the
Prolonged ileu s m ay be d ifficu lt to d istinguish from anastom osis is to the anal verge, the higher the p robability
mechanical sm all bow el obstru ction. CT scan is help fu l in of leakage. Several stu d ies have noted that anastom oses
assessing the p ossibility of intraabd om inal abscess and to d istal to 7 cm from the anal verge are at the highest risk for
d eterm ine w hether the p atient has an ileus or a m echanical leakage (25). H istorically, leakage occu rred in 30% of low
sm all bow el obstru ction (24). In the absence of other p elvic anastom oses. Contem p orary rates are 10%. The
pathology, su p p ortive care w ith nasogastric d ecom p res- im provem ent m ay be d u e to the practice of air insu fflation
sion is all that is necessary. Most partial m echanical sm all at the tim e of creation of the anastom osis to verify the
bow el obstru ctions resolve w ithin 1 w eek w ith this p lan. absence of a leak and d u e to im p roved stap ling d evices.
Because ad hesions m ay be very d ense in the perioperative Diversion of stool in the form of an ostom y d oes not p re-
period , reop eration for p artial sm all bow el obstru ction vent leak.
shou ld be avoid ed in the absence of signs of intestinal Typically, anastom otic leak is d iscovered 5 to 7 d ays after
ischem ia. For p rolonged postoperative ileus, an alternative surgery (Fig. 38.1). H ind sight usually reveals earlier signs
is continu ed bow el rest and nu tritional sup port in the ou t- that should make the surgeon more suspicious of a leak,
patient environm ent. including fever, leukocytosis, localized or generalized ten-
d erness, generalized ileus with abd ominal d istention, and
Leak tachycard ia. CT scan is helpful to d eterm ine w hether there is
Anastom otic healing occurs as a fu nction of the patient’s an associated abscess. In cases where leak is suspected, a
general cond ition, and , im portantly, of local factors su ch as gentle Gastrografin enema may assist the d iagnosis.
blood su p p ly, tension, and the health of the bow el utilized . Once recognized , aggressive m anagem ent of the anas-
The m esentery shou ld p rovid e ap p rop riate vascu latu re to tomotic leak is m and atory. Patients w ith generalized p eri-
the bow el, w ith clearance of 5 m m from the cu t ed ge. Ten- tonitis requ ire exp loration. At exp loration, d ism antling of
sion on the anastom osis m ay cau se d isru p tion and com p ro- the intraabd om inal anastom osis and fecal d iversion is the
mise of the blood su p ply. Thin, healthy bow el is preferred goal. In the case of a d istal left-sid ed anastom osis, the
to thickened , inflam ed , or ed em atous bow el. inflam m atory response m ay be so intense as to im pair safe
FIGURE 38.1. Algorithm for anastomotic

1
leak. Drainage may usually be accomplished Extravasation of dye Subtle signs/symptoms
percutaneously, but it may be accomplished
either transrectally or by open laparotomy if
necessary. 2If the abscess is associated with
an anastomotic leak, a fistulogram or con- Generalized Localized Exclude other
trast study may be helpful to determine the peritonitis peritonitis sources of sepsis
location, size, and so on, which may be help-
ful to determine subsequent management.
3,4
In the case of low or distal anastomoses,
the inflammatory response may be so intense Resuscitate; CT scan
that dismantling the anastomosis may be dif- antimicrobials;
ficult. In this situation, lavage, wide drainage, mark site for stoma;
and proximal diversion is the most appropri- explore
ate operative approach. Drainage1
Identified leak Small or

unidentified Sinogram or
leak; contrast study2
distal
Proximal anastomosis3
anastomosis;
exteriorize Inadequate drainage
both ends
Drain
anastomosis;
Distal proximal
anastomosis; diversion
Hartman’s
procedure4
recognition of the anastom osis. In these cases, p ru d ent m obilization. If a p resacral vein is torn, bleed ing is brisk
management includ es p roxim al d iversion w ith lavage of bu t m ay be controlled w ith tacks, bone w ax, or cau tery.
the p eritoneal cavity and p lacem ent of d rains near the Massive hem orrhage occu rs in p atients w ho have basiver-
anastom osis. tebral connections to the p resacral vein. This anatom y is
If the p atient has low -grad e sep sis and the leak is su btle encou ntered in ap p roxim ately 15% of ind ivid u als (26).
enough to require a contrast stu d y to d em onstrate and if Occlu sion w ith the d irect p ressu re is necessary for tem p o-
there is no concu rrent abscess, close observation w ith intra- rary arrest of the hem orrhage; p erm anent hem ostasis is
venou s antibiotics and bow el rest is initiated . If there is fail- p ossible by inserting a thu m btack into the sacru m over
ure of im p rovem ent, exploration is necessary. the area of bleed ing.
Abscess Anastomotic Hemorrhage

An intraabd om inal abscess m ay be the presenting sign of The incid ence of anastom otic hem orrhage is low, w ith an
acu te inflam m atory cond itions su ch as app end icitis, d iver- incid ence of 0.5% to 1% (27). Many anastom otic bleed s are
ticu litis, p erforated colon cancer, or Crohn d isease. In the self-lim ited and d o not requ ire intervention. Gastrointesti-
case of elective colorectal su rgery, postop erative intraab- nal hem orrhage in the early p ostop erative p eriod can be
d om inal abscess m ay be d u e to a break in techniqu e— challenging to m anage. An u p p er gastrointestinal sou rce
spillage of enteric or colonic contents, especially into a shou ld be exclu d ed . Distal anastom oses m ay be view ed
hem atom a or other d evitalized tissu es. It m ay also be the end oscop ically and controlled w ith injections of d ilu te ep i-
resu lt an anastom otic leak. CT scan is the surest means to nep hrine or short bu rsts of cau tery. The m anip ulation m ay
d eterm ine the p resence of an abscess. Althou gh u ltrasou nd increase the incid ence of anastom otic leakage. More proxi-
may d ocu ment the am ount and the location of flu id , there m al anastom oses m ay requ ire exp loration for control. If
are no sp ecific sonographic characteristics to d istingu ish sutu re reinforcem ent is not effective or if the bleed ing point
free p ostop erative fluid from an abscess cavity. Abscesses is not obviou s, d ism antling the anastom osis w ith resection
are u su ally id entified at a tim e w hen reentry into the and reanastom osis m ay be requ ired .
abd om en m ay be d ifficult or hazard ous, and thu s p ercu ta-
neous d rain placem ent is often a safer and less m orbid Splenic Injury
option for abscess d rainage. To treat bacterem ia, antibiotics Splenic inju ry m ay occu r d uring operations in w hich the
are ind icated . sp lenic flexu re is m obilized (3%) (28). The inju ry is u sually
sm all, involving a cap su lar tear at the anterior or m ed ial
Fistula su rface of the sp leen’s inferior p ole. The inju ry is cau sed by
Fecal fistu la m ay be the expression of an intraabd om inal d isru p ting the norm al sp lenic attachm ents or by traction
leak or abscess. CT scanning is necessary to id entify the on the om entu m . In the case of inju ry cau sed by traction on
abscess and to d irect appropriate d rain placem ent. Antibi- the om entu m , the inju ry m ay extend to the splenic hilum .
otics and su p p ortive care are initiated . In the absence of To avoid su ch inju ries, the d istal om entu m shou ld be m obi-
d istal obstru ction, foreign bod y, rad iation, or inflam m atory lized p rior to the initiation of sp lenic flexu re m obilization.
bow el d isease, m any fistulas resolve. Low -ou tp u t d istal There are several techniqu es to p reserve the sp leen
colonic fistulas d o not routinely requ ire p arenteral nutri- (Fig. 38.2). Pressure, topical hemostatic agents, and cautery
tion. Fistu las originating from p roxim al sm all bow el or can be used for hemostasis for small injuries. For larger
proxim al colonic sou rces m ay require this ad d itional su p - injuries, the spleen must be mobilized so that it becomes
portive care. Fistu las that d o not resolve or recu r m ay nearly a mid line organ. For larger parenchymatous injuries,
requ ire su rgical correction once the acu te inflam m ation has an absorbable mesh may be u sed to w rap the sp leen to facil-
subsid ed (Fig. 38.1). itate tamponad e.
Shou ld these m easu res fail, sp lenectom y is ind icated .
Presacral Hemorrhage The lifelong risk of p ostsp lenectom y infection is nontriv-
Preservation of the p resacral fascia is p aram ou nt to p re- ial. Protective vaccination shou ld inclu d e encap su lated
venting this com p lication, w hich occu rs d u ring rectal bacteria su ch as Streptococcus pneumoniae (p neu m ococcu s),
Pack Mobilize spleen Segmental splenic resection4 FIGURE 38.2. Algorithm for intraoperative
splenic capsular tear. 1Cautery placed on a
high setting may be used to achieve hemo-
stasis. 2Topical agents such as thrombin
Cautery1 Splenic wrapping3 Splenectomy with Gelfoam may be used in addition to the
above measures. 3Use of the omentum or
polyglycolic mesh may facilitate hemostasis.
4
Preservation of a portion of the spleen in the
Topical agents2 Topical agents2 Prophylactic vaccination absence of central arterial supply may not
maintain immunocompetency.
Haemophilus influenzae (typ e B), and Neisseria meningitidis.

Recognition of Suspect
Pneu m ococcu s is the m ost com m on and is associated w ith intraoperative injury ureteral ligation
a m ortality rate of 60%. The vaccination for p neu m ococcu s
(Pneu m ovax, Merck, Sharp & Dohm e, West Point, N ew
York) u tilizes a 23-valent p olysaccharid e cap su lar vaccine,
Suspect transection Dissection to
w hich is 90% effective in ad u lts old er than 55 years. The
or laceration identify site2
reim m u nization sched u le is every 5 to 10 years. Vaccina-
tion for H. influenzae is now ad m inistered to m ost child ren.
Im m u nity from the initial vaccination series m ay not be
su fficient in the asp lenic host, and rep eat vaccination or Give intravenous methylene Remove ligature
blue1 or indigo carmine to
d eterm ination of effective titers m ay be necessary. Vacci- identify location
nation for m eningococcu s is u nnecessary for the asp lenic
patient, excep t w hen traveling to an area w ith increased
risk.
Extravasation of dye If nonviable
Ureteral Injury
Inflam m ation, rad iation, previous su rgery, or m alignancy
alter the anatom ic relationship of the colorectum and the Surgical repair3
ureter and is associated w ith iatrogenic u reteral inju ry. For
colorectal su rgery, an incid ence of 0.3% to 10% has been FIGURE 38.3. Algorithm for intraoperative ureteral injury. If the ureteral injury
is confirmed urologic consultation is indicated. 1Administration of methylene
reported (29). Recognition of inju ry is critical, since im m e-
blue causes the urine to have a blue color and may transiently decrease oxy-
d iate rep air resu lts in im p roved healing. Delayed recogni- genation as measured by pulse oximetry. Indigo carmine is not associated with
tion is associated w ith significant m orbid ity, and it this transient decrement. 2If the ureter is not able to be clearly delineated, cys-
increases the incid ence of nephrectom y sevenfold (30). totomy with passage of a ureteral catheter proximally may aid in the identifica-
tion. 3Proper surgical repair depends on the injury’s area and extent. Proximal to
In colonic op erations, the left ureter is m ore com m only the pelvic rim, a ureteroureterostomy may be used. To facilitate a tension-free
injured than the right u reter. The abd om inal u reter origi- repair, not only is the ureter mobilized but also both the bladder and the kidney
nates at the renal pelvis and travels su perficial to the psoas may be mobilized. The repair should be spatulated, sutured with absorbable
mu scle. As the u reter enters the pelvis, it crosses the bifu r- monofilament suture over a stent, and drained. Injuries to the ureter within 5 cm
of the bladder may be repaired with a ureteroneocystostomy. To minimize the
cation of the iliac arteries, p assing posteriorly and inferi- tension on this repair, a psoas hitch or Boari flap may be indicated.
orly along the p elvis to the levator m u scles before entering
the posterior blad d er. In w om en, the d istal ureter passes in
the u reterosacral ligam ent behind the ovary and continu es Althou gh preoperative ureteral stenting in situations in
inferiorly in the broad ligam ent. In colorectal proced u res w hich a d ifficu lt d issection is anticip ated has not been
several typ es of inju ries may occur: crush, partial or com - show n to d ecrease the incid ence of inju ry, stenting m ay
plete transaction, ligation, or d evascu larization. facilitate id entification of inju ries (31). A sm all num ber of
These inju ries occu r in association w ith ligation of the com p lications have been d ocu mented , inclu d ing failu re to
inferior m esenteric vessels, d ivision of the lateral rectal p ass the stents, hem atu ria, and reflex anu ria u p on stent
stalks, and su rgery in the cu l-d e-sac or sacral p rom ontory rem oval.
or d u ring rep eritonealization. Intraop eratively, if the su r-
geon is su sp iciou s of u reteral inju ry or is u nable to id en- Bladder Dysfunction
tify the u reter, ad m inistration of ind igo carm ine or This com plication of proced u res on the rectu m is m ultifac-
m ethylene blu e m ay be help fu l (Fig. 38.3). Unfortu nately, torial. Inju ry to the p arasym p athetic nerves that innervate
these m aneu vers d o not aid in the id entification of a the d etru sor m u scle or to the sym p ath etic nerves that
u reteral ligation bu t only of a transection inju ry. If transec- innervate the blad d er neck, trigone, and u rethra d uring the
tion is su sp ected , a retrograd e stud y, either w ith contrast or p elvic d issection m ay be contribu tory. Postop erative blad -
via cystoscop y w ith stent placem ent, m ay id entify the d er d istension, prostatic hypertrophy, m ed ication, and pain
injury (Fig. 38.3). m ay all contribu te.
If an inju ry is id entified , a u rologist should be consu lted Blad d er d ysfunction occurs in 20% to 30% of patients fol-
to perform the rep air. The princip les involved in rep air low ing rectal d issection (32). Leaving the Foley catheter in
includ e d ebrid em ent of d evitalized tissues, a tension-free place for several d ays after surgery may allow for some of
anastom osis that is spatulated and rep aired w ith fine, the immediate operative edema, pain, and diuresis to
absorbable, m onofilam ent sutures over a stent, w ith resolve. The patient w ho is maintained on medication for
d rainage. For m ost injuries, u reteroureterostom y is su ffi- prostatic hypertrophy should reinitiate this med ication for
cient. With significant tissue loss, the kid ney, blad d er, and 48 hours prior to an attempt at spontaneous void ing. If the
ureter m ay requ ire ad d itional m obilization and ad vanced patient d evelops frequency, especially of small amounts of
reconstru ction, inclu d ing a psoas hitch, Boari flap, uretero- urine, the catheter is replaced and the trial of void is reiniti-
neocystostom y, or transureteroureterostom y (Fig. 38.4). ated in a few d ays. Urinalysis shou ld be p erform ed to
Pull
through
Psoas
muscle
Ureter
HRF '0
4
Injury Reimplanted
ureter
B
FIGURE 38.4. Surgical options for repair of ureteral injury. A: Ureteroureterostomy. The repair is completed in a tension-free manner.
The ends are spatulated, and monofilament absorbable suture is used to affect the repair over a stent. The area is drained. B: Psoas hitch.
In the pelvis, if the ureter is injured, the ureter may be reimplanted into the bladder and tension on the repair alleviated by approximation
of the superior bladder to the psoas tendon. (continued )
FIGURE 38.4. (Continued) C: Boari flap.

The bladder flap is spiraled and approxi-
mated to the psoas, with ureteroneocys-
tostomy.
HRF '0
Injury
4
Bladder flap
exclud e a urinary tract infection as a contributing factor. Fail- Fecal Incontinence

ing these measures, with intermittent catheterization, most For most lesions in the midd le and lower third of the rectum,
patients improve with time, suggesting that nerve dysfunc- restoration of intestinal continuity has become a standard
tion is most likely second ary to traction injury or postopera- practice. The dissemination of sphincter-sparing procedures
tive ed ema. In a minority of patients, prostatic hypertrophy has resulted in the recognition of fecal incontinence as a com-
is revealed and may require urologic management. plication of rectal cancer surgery. The incidence of this out-
Sexual Dysfunction come in very low anastomoses may reach 20% to 50% (36,37).
The etiology of this d ysfunction is multifactorial. The
Inju ries to the sym p athetic and p arasym p athetic nerves in introd uction of stapling d evices through the anus may injure
the pelvis cau se sexu al d ysfunction. Sexual d ysfu nction the sphincter and rectal mobilization may lead to denerva-
ranges from 15% to 60% (33,34). The neu rologic inp u t for tion of the pelvic muscles. The absence of the rectal reservoir
erection arises from the parasymp athetic nervi erigentes, and rad iation to the sphincter complex contribute to fecal
w hereas sym p athetic inp u t is requ ired for ejacu lation. incontinence. Clustering of bow el movements, incomplete
Wom en exp erience less frequ ent d ysfu nction. The contrib- evacuation, soiling, and urgency are ad d itional troublesome
utory factors for both m en and w om en are m u ltifactorial, sym p tom s. Med ical treatm ent w ith fiber, antid iarrheal
includ ing age, p reoperative libid o, the availability of a agents, and barrier cream to protect the perianal skin may
partner, and rad iation. improve symptoms.
Preservation of the m ain nerve trunks is p ossible and
may d ecrease the incid ence of sexual d ysfu nction. The
sacral nerve roots 2, 3, and 4 m ay be injured d uring p oste- Femoral and Peroneal Neuropathies
rior rectal m obilization ju st above the sacral p rom ontory. Fem oral neu rop athies are u su ally d u e to self-retaining
The nerves m ay be seen in the film y p lane of d issection ju st retractors. An incid ence of 0.7% has been rep orted follow -
d eep to the p roxim al m esorectum . The pelvic p lexu s m ay ing colon resection (38). Inju ry occu rs as the fem oral nerve,
also be inju red d u ring ligation of the rectal stalks. the largest branch of the lu m bar p lexu s, p asses throu gh the
Sexu al d ysfu nction m ay sp ontaneou sly im p rove over p soas m ajor m u scle. Either d irect retraction of the psoas
the 6-m onth to 12-m onth period follow ing proctectom y. m u scle w ith the nerve or im p ingem ent of the nerve against
Sild enafil (Viagra) im p roves erectile d ysfu nction in nearly the lateral abd om inal w all cau ses inju ry. Patients at risk are
80% of these p atients and greatly alleviates this sou rce of those w ho are thin, w ho are short, or w ho have m inim al
postop erative m orbid ity (35). rectu s m u scles. N eu rop athy can be avoid ed by ap propriate
placem ent of retractor blad es so that only the anterior and should a leak d evelop. Most agree that a breach in anasto-
lateral abd om inal w alls are m obilized . motic integrity, und ue anastomotic tension, and high-d ose
The p atient p resents w ith w eakness of the qu ad ricep s immunosuppression are indications for diversion.
fem oris, hyp oesthesia of the anterom ed ial thigh, and
d ecreased or absent patellar tend on reflex. Early in the Pouch–Vaginal Fistula
postop erative p eriod , the signs and sym ptom s of inju ry This type of fistula occurs w ith an incid ence of 4% to 16%
may not be obviou s in the patient w ith an epid ural catheter after proctocolectomy and is associated w ith significant
for p ain control. Prognosis for recovery is good . Physical morbidity. Seen early after restorative proctocolectomy, fis-
therap y shou ld be initiated , w ith the expectation that tula is often due to an infectious anastomotic source. Patients
90% of p atients w ill recover (39,40). complain of pain, fever, and purulent vaginal discharge.
Peroneal nerve injury is d ue to positioning. Du ring d is- Careful exam ination should be completed w ith attention
tal colonic and rectal proced u res, w ith m od ified lithotomy given to the vaginal septum. If the examination fails to
position for access and w ith placem ent of the legs in stir- reveal signs of fistula but clinical suspicion remains, a w ater-
ru ps, the calves m ay be subjected to p rolonged lateral p res- soluble contrast enema may demonstrate the fistula.
sure. The p eroneal nerve is at risk as it cou rses from the Repairs take several forms. If the pouch is neither scarred
posterior asp ect of the knee, p assing laterally arou nd the nor inflamed, advancement of a pouch-based flap is usually
head of the fibu la. Pressu re, if there m u st be any, shou ld be the first approach. If this procedure is difficult, concomitant
med ially p laced . Id eally, p ressu re w ou ld be on the heels, loop ileostomy may be required. If there is significant scarring
and all other p ortions of the low er leg shou ld be ad e- or inflammation of the distal pouch, consideration should be
qu ately cushioned and free from com pression. given to an anal advancement procedure. If there is circum-
The clinical p resentation of p eroneal nerve inju ry is ferential scarring, transanal or abdominal approaches to read-
footd rop . The rapid test to d ocu m ent intactness is d orsi- vance the pouch, with reestablishment of a diverting stoma,
flexion of the great toe. Fortu nately, w ithou t p reexisting may be necessary. In cases where the pouch was completed
neu rop athy, p rognosis for this injury is excellent. for a diagnosis of ulcerative colitis, this complication may
indicate a true diagnosis of Crohn disease. Overall, approxi-
Wound Infection mately half of the patients will achieve healing, with 25% hav-
Wou nd infections are a com m on com plication of colorectal ing persistent fistulas and 22% requiring pouch excision (46).
surgery and —althou gh rarely life threatening—are associ-
ated w ith increased cost and length of stay (41). Althou gh, Pelvic Abscess
historically, p atients u nd ergoing elective colorectal su rgery The incid ence of pelvic abscess follow ing restorative proc-
und erw ent a m echanical bow el preparation in an effort to tocolectom y is ap p roxim ately 5%. The etiology is u sually
red u ce the risk of infectiou s com plications, m u ltip le m eta- contam ination of the p resacral sp ace d u ring the d issection
analyses have show n no benefit of bow el prep aration in or a leak of the p ou ch–anal anastom osis. Presenting com -
red u cing the risk of postoperative w ound infection (42,43). p laints inclu d e p elvic or low back p ain, accom panied by
Proced u re and p atient factors includ ing blood transfu sion, fever and leu kocytosis.
long op erative tim e, obesity, and steroid therapy can con- CT scan is helpful for d iagnosis and to plan the thera-
tribu te to w ou nd infections. The m ainstay of treatment is p eu tic strategy. CT-gu id ed d rainage m ay be p ossible. If the
opening the w ou nd to evacu ate pus in a tim ely m anner, fol- p atient has a d iverting ileostomy, the stom a shou ld be left
low ed by local w ou nd care in the ou tpatient setting. in p lace u ntil the sep tic p rocess has resolved . Unfortu-
nately, p elvic sep sis is strongly associated w ith p ouch d ys-
fu nction and is resp onsible for nearly half of the cases
■ Complications after ileal pouch–
requ iring p ou ch excision (47). If the ileostom y has been
anal anastomosis closed or no ileostom y had been m ad e, strong consid era-
Leak tion for establishm ent of an ileostom y shou ld be given.
Anastomotic leakage follow ing an ileal pouch–anal anasto-
mosis proced ure occurs in up to 12% of patients (44,45). Stricture
Leakage may lead to significant morbidity, includ ing local- Strictures at the anastomosis are common but usually not
ized or generalized peritonitis, abscess formation, fistulas, problematic. In approximately 5% to 15% of patients, signifi-
anastomotic stricture, and a dysfunctional pouch. The pres- cant stricturing occurs (44,48). Strictures may be palpable
ence of an asymptomatic leak may be documented by a con- prior to ileostomy closure and may be manually d ilated .
trast stud y obtained prior to ileostom y closure. If present, Lew is et al. (49) identified some contributory factors, includ -
closure is d eferred for several months, prior to w hich ing use of a sm all-d iameter stapling gun, construction of a
another contrast study documenting resolution is necessary. W-pouch, defunctioning ileostomy, and anastomotic dehis-
The routine use of d iverting ileostomy at the time of ileal cence w ith pelvic abscess. For strictures in which dilation is
pouch–anal anastomosis is controversial. Diversion does not not possible or has failed , investigators have d escribed a
prevent leak, but it eliminates some symptoms and sequelae technique for pouch advancement (50).
Pouchitis correctly sized aperture to avoid im prop er placem ent or

Pouchitis represents acute or chronic inflammation of the p ancaking. Pancaking refers to lack of air in the appliance,
ileal reservoir. Although it is common in patients w ith ulcer- w hich creates negative p ressu re and cau ses the ap p liance’s
ative colitis, pouchitis is essentially absent in those who have p lastic sid es to stick together, thu s p reventing stool from
had restorative proctocolectomy for polyposis. Pathogenesis p assing freely into the ap p liance. Other cau ses of effluent
is poorly understood and includ es bacterial stasis, ischemia, d erm atitis inclu d e an overfu ll ap p liance, an ap p liance that
recurrent ulcerative colitis, and fatty acid deficiency. Other is left on too long, or an excessively liqu id ou tp u t.
theories includ e overprod uction of nitric oxid e and free rad - Other etiologies relate to p reop erative and intraop era-
ical production (51). The incidence of pouchitis is not related tive m anagem ent. For exam p le, a p oor stom a site lead ing
to the type of pouch created . The prevalence of acute pouch- to p oor visu alization of the ap p liance or an inad equ ate seal
itis varies from 10% to 60% (52). How ever, 5% to 15% of m ay contribu te to leakage. Sim ilarly, the creation of a
patients suffer from chronic pouchitis, although only 1% to stom a that lacks an ad equ ate sp ou t w ill cau se leakage d eep
3% of the patients require pouch excision (53). to the ap p liance. Id eally, ileostom ies shou ld be created
Symptoms of p ou chitis includ e bleed ing, increased stool w ith a 2- to 3-cm sp ou t and shou ld be everted . Techniqu es
frequ en cy, abd om in al d iscom fort, an d fever. In ad d ition to enhance eversion inclu d e circu m ferential su tu re p lace-
to these clinical sym p tom s, end oscop ic find ings inclu d e m ent before tying d ow n. The m esentery of the end of the
mucosal ed ema, granularity, friability, loss of vascular pat- ileum m u st p rovid e good blood sup ply w ithout tension;
tern, mu cou s exu d ates, and ulceration, w ith histologic evi- lack of these factors contributes to retraction.
dence of acute leukocyte infiltration and ulceration. Initial Allergic contact d erm atitis is cau sed by an antigenic
treatment includes administration of metronidazole. Alterna- resp onse to a stom al p rod u ct. A system atic review of possi-
tives include ciprofloxacin, erythromycin, and tetracycline. ble etiologic agents is necessary so that a nonoffend ing su b-
Topical anti-inflammatory agents, including steroid enemas, stitu te p rod u ct m ay be id entified .
mesalamine enemas, and suppositories, may be attempted. If Enterostom al nu rses are instru m ental for the p reop era-
there is no response, oral agents may be used to supplement tive siting, ed u cation, and continu ed su p p ort of these
local measures. Unfortunately, this strategy returns patients p atients. Their inp u t has been d ocu m ented to im prove the
to the regimens they so wanted to leave behind. Oral bismuth lives of ostom ates (58,59).
or other immunosuppressants, including azathioprine, may Prolapse
be successful in aborting symptoms. Ultimately, if the cond i-
Alth ou gh alarm in g to th e p atien t w h en p rolap se initially
tion persists, pouchitis may necessitate pouch excision.
occu rs, th ere is u su ally no fu nctional significance
Poor Pouch Function (Fig. 38.5). An overly large fascial d efect contribu tes to
the p ath op h ysiology. Prolap se is m ore com m on w ith
Although 85% of p atients are pleased w ith p ouch activ-
loop th an w ith en d stom as and is m ore com m on w ith
ity, a m inority w ill have p oor pouch function. The inci-
colostom ies th an w ith ileostom ies. In th e acu te settin g,
d ence of total failu re requiring pou ch excision, w ith the
osm otic th erap y w ith table su gar m ay sh rink an incarcer-
establishm ent of p erm anent ileostom y, is 3% to 10% (54).
ated p rolap se su fficiently to allow red u ction (60). The
The m ost com m on cau ses lead ing to p ou ch failu re inclu d e
pelvic sep sis, p ou ch fistulization, and Crohn d isease (55).
HRF '04
■ Stoma complications
Although m any com plications are avoid able w ith carefu l
creation and siting of the stom a and enterostom al nu rsing,
a significant nu m ber of patients w ill have problem s rang-
ing from a m ild skin irritation to parastom al hernia.
Dermatitis
Derm atitis is very com m on ( 30%), w ith m ost cases occu r-
ring d u ring the first year after stom a form ation (56). Con-
tact d erm atitis m ay take tw o form s: d u e to the stom al Prolapsed stoma
effluent or d u e to the pouch, its solvents, or ad hesives.
Effluent d erm atitis is an inflam m ation or excoriation of the
skin d u e to leakage of the stom a ou tput. More com m on in
patients w ith an ileostom y or urostom y, approxim ately
20% of colostom y p atients w ill have this type of d erm atitis
(57). Gu t enzym es and bile are irritating to the skin and
d am age the keratinized surface. Som e aspects m ay be cor-
rected w ith p atient ed u cation by teaching p atients to cu t a FIGURE 38.5. Stomal prolapse.
long-term p rolap se rate for all typ es of stom as is ap p rox-

im ately 11% to 12% (61,62).
Simple prolapse may be repaired by mobilizing the
mucocutaneous junction and resecting the red und ant bow el
through a local incision. Recurrence may require laparotomy
and resiting of the stoma. For patients in w hom a fu ll
laparotom y is ill-ad vised w ith p rolapse from either a loop
or transverse colostomy, a proced ure that strips the red un-
d ant mucosa w ith plication of the bow el from the apex to
the mucocutaneous junction may be perform ed (63).
Retraction
Stom al retraction occu rs as a resu lt of the failu re to m obi-
lize sufficient bow el and its m esentery to avoid tension.
Retraction occu rs in 1% to 6% of colostomies (64,65) and 3%
to 17% of ileostom ies (62). Retraction perm its the stom al
effluent to seep u nd erneath the app liance and m ay result in
pou ch loosening.
Althou gh local proced u res m ay be su fficient for the FIGURE 38.6. Parastoma hernia associated with nonprotruding stoma may
management of retraction, laparotomy is often necessary. be associated with obstruction, peristomal skin care, and pouching difficulty.
For left-sid ed end colostomies, m obilization of the splenic
flexu re m ay be required to prod uce a tension-free mu cocu-
For colostom ies, strictu re alm ost alw ays occurs at the
taneous apposition. If the mesentery is provid ing tension,
skin level. Since m ost colostom ies are now m atu red at the
the use of the “end -loop” or “d ivid ed loop” stoma, in w hich
tim e of creation, strictu re is the resu lt of necrosis of the d is-
the stapled end s are left in place, w ith opening and matura-
tal stom a. Minor strictu re m ay be m anaged by d aily m an-
tion of only the stapled proximal end , may provid e ad d i-
u al d ilation. Long length narrow ing, esp ecially w hen d ue
tional length.
to ischem ia, tension, or Crohn d isease, requ ires laparotom y
for com p lete m obilization.
Necrosis
Early p ostop erative necrosis is second ary to vascu lar Parastomal Hernia
insu fficiency at the d istal ed ge of the stom a, either d u e to Parastomal hernias are challenging p roblem s, occurring in
arterial insu fficiency or venou s congestion. This com p lica- u p to 37% of colostom ies and 16% of ileostom ies (58). Sim i-
tion is cau sed by m esenteric ischem ia w ith overtrim m ing lar to other typ es of incisional hernias, p arastom al hernias
of the m esentery from the end of the bow el, inad equ ate are m ore com m on in p atients w ith obesity, m alnu trition,
p roxim al m obilization, or too tight a fascial op ening. steroid d ep end ency, or w ou nd infection (Fig. 38.6).
Im m ed iately p ostop eratively, a norm al stom a m ay ap p ear Ind ications for rep air inclu d e d ifficu lty w ith ap p liance
d u sky d u e to venou s engorgem ent or stom al ed em a; this ad herence, pain, incarceration or strangu lation, poor loca-
ap p earance shou ld evolve to a bright p ink color as these tion, or an association w ith other stom a-related problem s
p rocesses resolve. N ecrosis is m ore likely in p atients w ho such as strictu re. Options to rep air the hernia locally includ e
are obese and in those w ho have u nd ergone an em ergent application of mesh. N ew er op tions for mesh repair or rein-
p roced u re, encom p assing 1% to 10% of colostom ies and forcem ent inclu d e p orcine collagen, w hich is resistant to
1% to 5% of ileostom ies (66). absorp tion, p erm itting a scaffold for native collagen, resist-
If necrosis is su spected , the im m ed iate question relates ing infection and an inflam m atory resp onse.
to the d ep th and extent of necrosis. This d eterm ination is The recu rrence rate of p arastom al hernia is qu ite high,
facilitated by the placem ent of a clear glass or plastic tu be ranging from 33% to 50% after relocation (67), 50% to 100%
insid e the stom a and shining a p en flashlight d ow n the bar- after fascial rep air, and 50% after p rosthetic repair. In ad d i-
rel. If necrosis extend s to the level of the fascia, reop eration tion, after relocation nearly half of p atients w ill d evelop an
is necessary to p revent tension, retraction, strictu re, or p as- incisional hernia.
sage of fecal m aterial into the p eritoneal cavity.
■ ANORECTAL SURGERY
Stenosis
Stom al stenosis occurs in 2% to 10% of end ileostom ies and
■ Hemorrhoidectomy
colostom ies (58). The stricturing of Crohn d isease m ay Vascu lar “cu shions” consisting of bu nd les of su bm u cosa
increase stom al stenosis (62). At the m inim u m , stenosis w ith an arteriovenou s netw ork, sm ooth m u scle, and elastic
may cau se loud passage of air and bow el content into the and connective tissu es are p resent in every patient. The
app liance, and at w orst, it m ay cau se obstruction. term hemorrhoids u su ally refers to p athologic cond itions
associated w ith these “cushions.” Prim ary internal hem or- With a resid u al 500 cc, the catheter shou ld be rem oved ,
rhoid s lie in constant positions: right anterior, right p oste- and a trial of void ing reinitiated . Urinary retention m ay
rior, and left lateral. External hem orrhoid s are d istal to the also be an early sign of severe p erineal infection—a rare
d entate line, w hereas internal hem orrhoid s are proxim al to com plication of hem orrhoid ectom y.
the d entate line.
Fecal Impaction
■ Early complications of hemorrhoidectomy Fecal im p action is seriou s, althou gh rare, occu rring in 0.4%
Bleeding of p atients after hem orrhoid ectom y (72). Most patients
d read their first p osthem orrhoid ectom y bow el m ovem ent
Bleeding that occurs in the recovery room is due to technical
d u e to the anticip ated d iscom fort. They m u st be w arned
error, most commonly the result of inadequate ligation of the
that constipation that evolves into im paction is even more
vascular ped icle. To control significant hem orrhage, a Foley
u ncom fortable. Constip ation shou ld be p revented w ith
catheter w ith the balloon inflated can be inserted to tampon-
laxatives, stool softeners, oral fiber, ad equ ate hyd ration,
ade the hemorrhage as the operating room is prepared .
and activity.
Pain Im p action m ay be d ifficu lt to d iagnose p ostop eratively.
Perineal d iscomfort, lack of bow el fu nction, and overflow
The mod erate degree of anal pain and rectal spasm is com-
d iarrhea are d om inant sym p tom s. Discom fort ou t of pro-
mon after hemorrhoid ectomy. Pain not only is challenging to
p ortion to op erative trau m a is a com m on find ing. If rectal
manage but also contributes to urinary retention and fecal
examination is p ossible, the fecal bolu s is p alp able. A high
impaction. Multiple approaches have been used to minimize
enem a given w ith a red ru bber catheter m ay be all that is
this expected outcome. Ketorolac trometham ine has been
requ ired to allow stool egress. In cases w hen d iscom fort is
given intravenously, w ith subsequent recommend ations for
severe and d isim p action is not p ossible, evacu ation in the
the outpatient intake of anti-inflamm atory agents. In the
op erating room w ith the assistance of anesthesia m ay be
belief that low-grad e infection may contribute to pain,
necessary.
metronid azole has been given intravenously, w ith follow -up
outpatient d osing for 3 to 7 d ays. Although initially noted to
Late Complications of Hemorrhoidectomy
have positive responses, later studies reveal no efficacy (68).
Perioperative application of 0.2% glyceryl trinitrate oint- Anal Tags. After hem orrhoid ectom y, the anal area becom es
ment, in an effort to increase blood flow and relax the ed ematous. Occasionally, external thrombosed hemorrhoid s
sphincter muscles, has also been attempted , w ith mixed suc- m ay occu r, and in the resolu tion, a skin tag is left. Tags m ay
cess (69). Even postoperative pain pumps placed d irectly also sim p ly be a m anifestation of w ou nd healing. N uisance
into the anal canal have received some attention (69). skin tags m ay cause d iscomfort to the patient if they im pair
Severe anal p ain m ay be a sign of a p erianal hem atom a. local hygiene.
The d ressing shou ld be rem oved and the w ou nd insp ected .
Und u e tension in the closu re is the m ost likely cause of d is- Stricture. Rem oval of an excessive am ou nt of m u cosa, es-
com fort; it is better to leave a w ound open than to close it p ecially anod erm , is resp onsible for anal strictu re. Acu te
w ith excessive tension. m anagem en t of hem orrhoid s w ith extirp ation of all the
ed em atou s, in flam ed , or th rom bosed tissu e m ay lead to
Urinary Retention in ad equ ate elastic an al tissu e, w h ich , as h ealin g p ro-
Urinary retention occu rs w ith an incid ence from 3% to gresses, lead s to a fibrou s scar. This com p lication m ay re-
20% (70,71). This com p lication’s etiology is m u ltifactorial. su lt in the elective setting as w ell, and ad equ ate anod erm al
Contribu ting factors inclu d e p rostatic hyp ertrop hy flu id brid ges are necessary to p reserve su fficient tissu e to p re-
overload , rectal pain and spasm, high ligation of the hemor- ven t its occu rren ce. In d icators to h elp p revent this com -
rhoidal ped icle, heavy suture material, tight packing, bulky p lication inclu d e tension-free p lacem ent of a large-sized
dressings, anticholinergics, and narcotics (70). Anorectal sur- H ill–Fergu son retractor and at least 1-cm brid ges betw een
gery may d ecrease parasympathetic input to the d etrusor each excised area.
muscle, w hereas pain may increase sympathetic input to the If stricture is a long-term outcome of the procedure, post-
urethral sphincter, both contributing to spasm. operative dilation, ensuring the passage of stool, and main-
Intraop erative flu id s shou ld be lim ited to avoid p eriop - tained physician observation is necessary. If stricturing
erative blad d er d istension. Patients are asked to void p rior ensues and is epithelialized and fixed, anoplasty is indicated.
to entry into the op erating room , w here intravenou s flu id s Anop lasty involves m obilization of p erianal skin to
are lim ited to 500 m L or less. Patients w ho receive a local cover a d efect in the anal canal. If the strictu ring p rocess
anesthetic w ith sed ation have a d ecreased incid ence of this involves the sp hincter, a carefu l lateral sp hincterotom y
com p lication. m ay be ind icated as w ell. Anop lasty flap s take m any
If the p atient is u nable to void , the subject shou ld shap es, inclu d ing V–Y, Y–V, hou se, and rotational flap s.
und ergo catheterization. If resid u al is 500 cc, the catheter The strictu re’s length and d ep th, along w ith the local tis-
should be left in p lace, w ith a trial of void ing in 24 hou rs. su e availability, d ictate w hich flap is p referred (Fig. 38.7).
' 04
hrf
B
'04
hrf
C
FIGURE 38.7. Anoplasty for stricture/stenosis. A: Bilateral V-flaps advance into the anal canal. B: V–Y flap may be
repeated bilaterally. C: House flaps are a modification of the V–Y flap, may be repeated on the contralateral side, and
may advance additional anoderm into the canal.
Mucosal Prolapse and Ectropion. Inad equ ate rem oval of re- When failu re of sp hincterotom y is d ocu m ented , an u ltra-
d u nd ant m u cosa at the tim e of hem orrhoid ectom y con- sou nd and anal m anom etry are ind icated p rior to p erform -
tribu tes to p rolap sing m u cosa. Patients w ill rep ort a w et ance of a second lateral sp hincterotom y on the op p osite
lum p of tissu e d ischarging m ucu s that requires m anual resid e. If the initial sp hincterotom y is anatom ically correct
d u ction. The w et p erianal tissu e contributes to local p ru ri- and fears of incontinence are p resent, treatm ent w ith botu -
tu s. Ru bber band ligation m ay effectively d eal w ith this linu m toxin is ind icated . The p ossibility of another process,
com plication. p articu larly Crohn d isease, m u st be exp lored .
An ectropion results w hen rectal mucosa descends and
heals outside the anal canal. Ectropion may result from Incontinence. The length of internal sphincter that m ay be
mobilization of the rectal mucosa and fixing the mucosa to safely d ivid ed to treat p atients w ith anal fissu re and the
the anod erm. Similar to m ucosal prolapse, the “w et anus” closed versus open approach to sphincterotomy continue to
prod uces mucus that contributes to discomfort and pruritus. be d ebated . Althou gh m ost sym p tom s are d u e to inconti-
If the ectrop ion is evid ent in a lim ited area, the m u cosa nence to flatu s, w hich u su ally resolves, there is p ersistence
may be excised , w ith su tu re fixation of the remaining d istal of fecal incontinence of 1% to 2%. When the length of
rectal ed ge to the p roxim al sphincter. If the ectrop ion is sp hincter d ivid ed is exam ined by u ltrasou nd , m ore sphinc-
more p ronou nced , an anop lasty m ay be ind icated . ter m ay have been transected than w as intend ed (79). With
short follow -up, a 0.5-cm open sphincterotomy yield ed only
Incontinence. Anal sensation m ay be im p aired in u p to 50% a 3% incid ence of p ostp roced u ral incontinence to fluid and
of p atients after hem orrhoid ectom y, bu t by 6 w eeks, the flatu s (80). Others have su ggested tailoring the length of
m ajority resolve their sym p tom s (73). Classically, hem or- sp hincter d ivid ed , d ep end ing on the length of the fissu re,
rhoid ectom y rem oves vascu lar tissu e su p erficial to the w ith no incid ence of incontinence of feces or stool leakage
sphincter m u scles. The eld erly are esp ecially at risk for this (81). Preop erative assessment of continence of gas and stool
comp lication. Careful preoperative questioning is necessary is essential for ap p rop riate p atient selection.
to d iscern preexisting incontinence, although the symptoms
may be m ild .
■ Anorectal abscesses
Anorectal abscess is a com m on su rgical em ergency. In the
■ Anal fissure
acu te p hase the abscess p rod u ces signs of inflam m ation:
A fissu re is a p ainfu l linear tear or u lcer in the anal canal, erythema, p ain, heat, and loss of fu nction, seen at or near
d istal to the d entate line that m ay extend to the anal m ar- the anal verge. However, an intersphincteric abscess may not
gin. Prim ary fissu res are m ost often d ue to a change in be visible at this level and may require examination under
bow el habits and are located p osteriorly, w ith 10% in anesthesia both for diagnosis and management. Likewise, a
w om en and 1% in m en located anteriorly. Second ary fis- d eep ischiorectal abscess may be difficult to detect on prelim-
sures are d u e to inflam m atory bow el d isease, sexu ally inary physical examination, especially in the im m u nocom -
transm itted d iseases, neoplasm s, or trau m a and are located p rom ised host.
laterally. The p resence of an abscess m and ates su rgical d rainage.
At least 85% of acu te fissu res w ill resp ond to m ed ical Although d rainage m ay often be accom plished in the
management (74,75). Relief of constip ation and m anage- office, large abscesses, p ain w ithou t an ap p reciable sou rce,
ment of sp asm w ith a high-fiber d iet, stool softeners, sitz significant cellu litis, or an u ncoop erative p atient m ay
baths, and m ild analgesics are forem ost in the nonop era- requ ire examination and d rainage in the op erating room .
tive ap p roach. “Chem ical sp hincterotom y” w ith nitroglyc- The d rainage site is selected over the area of greatest flu ctu -
erin or nifed ipine ointm ent or botu linu m toxin can ance, close to, bu t not into, the sp hincter com p lex.
d ecrease anal resting pressure and increase blood flow to
facilitate healing. When m ed ical m anagem ent fails, lateral Complications of Abscess Drainage
internal sphincterotom y should be consid ered . Incomplete Drainage. The m ajor cau se of recu rrent anorectal
abscesses is inad equ ate d rainage. Most cau ses are d u e to
Complications of Internal Sphincterotomy cryp togland u lar d isease, and d rainage is necessary. If the
Abscess. The incid ence of abscess follow ing the closed in- origin cannot be ascribed to an anorectal sou rce, extra-anal
ternal sp hincterotom y is 1%, nearly alw ays associated sources includ e hid rad enitis sup purativa or pilonid al d is-
w ith an anal fistu la (76). As w ith other abscesses and fistu - ease. Chrabot et al. (82) reported that 70% of patients w ith
las related to cryp togland u lar d isease, p rincip les of treat- recu rrent abscesses have fistu la, w ith 30% of these patients
m ent inclu d e d rainage of the abscess and m anagem ent of having u nd ergone a p rior p roced u re.
the fistu la. H orseshoe abscesses p resent a sp ecial challenge and
can p resent recu rrently if the op p osite arm of the abscess is
Recurrence/Nonhealing Wound. Follow ing lateral internal incom p letely d rained . H orseshoe abscesses m ay occu r in
sphincterotom y, the recu rrence rate ranges from 0% to 12% three p lanes: the intersp hincteric p lane, the ischioanal
(77,78). Recent literatu re su ggests a failu re rate of 5%. p lane, or the su p ralevator p lane. Classically, the horseshoe
originates from the p osterior m id line and enters the d eep and m aintain continence. Althou gh the su rest m ethod for
postanal sp ace w ith arms extend ing anteriorly. The op p o- abolishing the infection is to p erform a fistu lotom y, this
site configu ration m ay also occu r. Entrance into the d eep techniqu e also d ivid es the m ost m u scle and m ay con-
postanal sp ace and d rainage, consisting of counterincisions tribu te to incontinence. Anterior fistu las, esp ecially in
placed rad ially, allow d rainage of pu s and rapid healing of w om en, m ay requ ire alternative m anagem ent, inclu d ing
the tracts. seton p lacem ent, m u cosal ad vancem ent flap s, or ligation
Intersp hincteric abscess m ay p resent w ithou t external of intersp hincteric fistu la tract, to achieve the goals ou t-
signs of inflam m ation in p atients w ho have sym p tom s of lined earlier.
an abscess. These patients often w ill not perm it d igital rec-
tal exam ination and w ill requ ire an exam ination u nd er Complications of Surgery for Fistula-in-Ano
anesthesia. Once the abscess is id entified , it is unroofed to Recurrence after Fistulotomy. After fistu lotom y, recu rrence is
the level of the d entate line, allow ing d rainage of the noted in 4% to 10% of cases (84). The most common cause of
offend ing cryp t. The ed ges of the w ou nd are sutu red for recu rrence is failure to id entify the p rim ary internal open-
hem ostasis, w hich also p erm its continued d rainage. ing. Other factors inclu d e com p lex fistu las w ith horseshoe
or upw ard extensions, prior surgery, and failure of ad equate
Necrotizing Perineal Infections. In few er than 1% of cases,
fistu lotomy for fear of cau sing incontinence. Crohn d isease
anorectal su p p u ration m ay be the cau se of necrotizing p er-
m ay also contribu te to recu rrence. Managem ent of acu te
ineal infection (83). Patients p articu larly at risk inclu d e
su p p u ration, follow ed by ad ju nctive im aging, by using u l-
those w ith im m u nocom p rom ise, inclu d ing d iabetes, renal
trasou nd or MRI, is help fu l to d efine the tract and the of-
insu fficiency, and inflam m atory bow el d isease. In these
fend ing anal gland .
high-risk grou ps, necrosis can occur in the absence of an ob-
viou s sou rce of infection, and system ic toxicity can be
Incontinence after Fistulotomy. The reported rates for incon-
severe.
tinence follow ing fistu lotom y range from 10% to 50% (85).
Aggressive resu scitation is required w ith p arenteral Although most agree that severance of the anorectal ring re-
antibiotics and extensive d ebrid em ent. Return trip s to the sults in incontinence, the question of how much muscle may
op erating room m ay be necessary to rem ove d evitalized be safely d ivid ed is still u nansw ered and m ay d ep end on
tissu e. The anorectal fistulous origin mu st be id entified and age, gend er, p reviou s anorectal or local p roced u res (e.g., an
app rop riately m anaged . ep isiotomy), and location (anterior vs. p osterior). When d e-
creased continence is a consid eration, staged m anagem ent
Fistula. Although not truly a com plication, a fistula remains
of the tract is m ost p ru d ent.
in 30% to 70% of p atients presenting w ith an abscess. The
abscess is the d istal exp ression of the fistu la.
■ REFERENCES
■ Fistula-in-Ano 1. Ad d iss DG, Shaffer N , Fow ler BS, et al. The ep id em iology of ap p en-
d icitis and app end ectom y in the United States. Am J Epidemiol 1990;132:
An abscess is u sually d ue to a cryptogland u lar infection 920–925.
from anal d u ct obstruction. Approxim ately half d o not heal 2. Lew is FR, H olcroft JW, Boey J, et al. Ap p end icitis: a critical review of
the d iagnosis and treatm ent in 1000 cases. Arch Surg 1975;110:677–684.
bu t eventu ate into a fistula. A fistu la is an abnorm al con- 3. Peck J, Peck A, Peck C, et al. The clinical role of noncontrast helical
nection betw een tw o ep ithelial stru ctu res—in this case, the com p u ted tom ograp hy in the d iagnosis of acu te ap p end icitis. Am J
mu cosa of the anal canal and the skin. Other cau ses of fis- Surg 2000;180:133–136.
4. Gale ME, Birnbau m S, Step hen GG, et al. CT ap p earance of ap p end ici-
tu las inclu d e inflam m atory bow el d isease, anorectal m alig- tis and its local com p lications. J Comput Assist Tomogr 1985;9:34–37.
nancy, actinomycosis, trauma, sexually transmitted diseases, 5. Oliak D, Yam ini D, Ud ani VM, et al. Initial nonop erative m anagem ent
and p elvic sep sis. for p eriapp end iceal abscess. Dis Colon Rectum 2001;44(7):936–941.
6. Bagi P, Du eholm S. N onop erative m anagem ent of the u ltrasonically
Althou gh m ost fistulas stem from an original inter- evalu ated app end iceal m ass. Surgery 1987;101:602–605.
sphincteric sou rce (56%), other fistulas are transsp hincteric 7. Deakin DE, Ahm ed I. Interval ap p end ectom y after resolu tion of ad u lt
(21%), su p rasp hincteric (4%), or extrasphincteric (3%). inflam m atory ap pend ix m ass—is it necessary? Surgeon 2007;5(1):45–50.
8. Lem ieu r TP, Rod rigu ez JL, Jacobs DM, et al. Wou nd m anagem ent in
Patients p resent w ith interm ittent pain, w hich m ay herald perforated ap p end icitis. Am Surg 1999;65:339–443.
blood y or p u ru lent d ischarge. An external opening is u su - 9. Sauerland S, Lefering R, N eu gebau er EA. Lap aroscop ic versu s op en
ally id entified , bu t the internal op ening m ay not be obviou s su rgery for su spected ap p end icitis. Cochrane Database Syst Rev 2004;(4):
CD001546.
on rou tine office anoscop y. 10. Fisher KS, Ross DS. Gu id elines for therap eu tic d ecision in incid ental
Intraop erative techniques for id entification of the inter- ap p end ectom y. Surg Gynecol Obstet 1990;171:95–98.
nal opening inclu d e the instillation of m ethylene blu e or 11. Fatu m M, Rojansky N . Lap aroscop ic su rgery d u ring p regnancy. Obstet
Gynecol Surv 2001;56(1):50–59.
hyd rogen p eroxid e. Com plex fistu las m ay requ ire u ltra- 12. H ard in D. Acu te ap pend icitis: review and u p d ate. Am Fam Physician
sou nd , CT, or MRI to d eterm ine the pathw ay of the tract 1999;60:2027–2036.
and the p ossible sou rce. 13. Yam ini D, H ernan V, Bongard F, et al. Perforated ap p end icitis: is it tru ly
a su rgical urgency? Am Surg 1998;64:970–975.
Managem ent is ind ivid u alized , bu t the goals are to 14. Storm -Dickerson TL, H orattas MC. What have w e learned over the past
erad icate the infection and the sou rce, p revent recu rrence, 20 years about app end icitis in the eld erly? Am J Surg 2003;185:198–201.
15. H u i TT, Major KM, Avital I, et al. Ou tcom e of eld erly p atients w ith 43. Slim K, Vicau t E, Lau nay-Savary MV, et al. Up d ated system atic review
ap pend icitis. Arch Surg 2002;137:995–1000. and m eta-analysis of rand om ized clinical trials on the role of m echani-
16. Painter N S, Bu rkitt DP. Diverticu lar d isease of the colon: a 20th centu ry cal bow el p reparation before colorectal su rgery. Ann Surg 2009;249(2):
p roblem . Clin Gastroenterol 1975;4:3. 203–209.
17. Ryan P. Tw o kind s of d iverticu lar d isease. Ann R Coll Surg Engl 1991;73: 44. Fazio VW, Ziv Y, Church JM, et al. Ileal p ou ch-anal anastom osis com -
73–79. p lications and fu nction in 1005 p atients. Ann Surg 1995;222(2):120–127.
18. H inchey EJ, Schaal PGH , Richard s GK. Treatm ent of p erforated d isease 45. Grobler SP, H osie KB, Keighley MR. Rand om ized trial of loop
of the colon. Adv Surg 1978;12:86–109. ileostom y in restorative proctocolectom y. Br J Surg 1992;79:903–906.
19. Ford e KA, Treat MR. Colonoscop y for low er gastrointestinal bleed ing. 46. Shah N S, Rem zi F, Massm ann A, et al. Managem ent and treatm ent ou t-
In: Dent TL, Stru d el SF, Tu rcotte JG, et al., ed s. Surgical endoscopy. com e of p ouch-vaginal fistu las follow ing restorative p roctocolectom y.
Chicago, IL: Yearbook Med ical Pu blishers; 1988:261–275. Dis Colon Rectum 2003;46(7):911–917.
20. Garland CF, Lilienfeld AM, Mend eloff AI, et al. Incid ence rates of ulcer- 47. Fazio VW, Wu JS, Lavery IC. Rep eat ileal p ou ch-anal anastom osis to
ative colitis and Crohn’s d isease in fifteen areas of the United States. salvage septic com p lications of p elvic p ou ches. Ann Surg 1998;228(4):
Gastroenterology 1981;81:1115–1124. 588–597.
21. Devroed e G. Risk of can cer in in flam m atory bow el d isease. In : 48. Senap ati A, Tibbs CJ, Ritchie JK, et al. Stenosis of the p ou ch anal anas-
Win aw er SJ, Sch otten feld D, Sh erlock P, ed s. Colorectal cancer: pre- tom osis follow ing restorative p roctocolectom y. Int J Colorectal Dis 1996;
vention, epidemiology and screening. N ew York, N Y: Raven ; 1980: 11:57–59.
325–334. 49. Lew is WG, Ku zu A, Sagar PM, et al. Strictu re at the p ou ch-anal anasto-
22. Ritchie JK. The resu lts of su rgery for large bow el Crohn’s d isease. Ann m osis after restorative proctocolectom y. Dis Colon Rectum 1994;37:
R Coll Surg Engl 1990;72:155–157. 120–125.
23. Jem al A, Mu rray T, Sam u els A, et al. Cancer statistics. CA Cancer J Clin 50. Fazio VW, Tjand ra JJ. Pou ch ad vancem ent and neoileoanal anastom o-
2003;53(1):5–26. sis for anastom otic strictu re and anovaginal fistu la com plicating
24. Frager DH, Baer JW, Rothpearl A, et al. Distinction betw een postopera- restorative proctocolectom y. Br J Surg 1992;79:694–696.
tive ileus and m echanical small-bow el obstruction: value of CT com- 51. Kuhbacher T, Schreiber S, Ru nkel N . Pou chitis: p athop hysiology and
pared with clinical and other rad iographic findings. AJR Am J Roentgenol treatm ent. Int J Colorectal Dis 1998;13:196–207.
1995;164(4):891–894. 52. Stein RB, Lichtenstein GR. Com p lications after ileal p ou ch-anal anasto-
25. Vignali A, Fazio VW, Lavery IC, et al. Factors associated w ith the occu r- m osis. Semin Gastrointest Dis 2000;11(1):2–9.
rence of leaks in stapled rectal anastom oses: a review of 1014 p atients. 53. Stahlberg D, Gu llberg K, Liljeqvist L, et al. Pou chitis follow ing p elvic
J Am Coll Surg 1997;185:105–113. p ou ch op eration for ulcerative colitis: incid ence, cu m u lative risk, and
26. Wang O, Shi W, Zhaw Y, et al. N ew concep ts in severe p resacral hem or- risk factors. Dis Colon Rectum 1996;39:1012–1018.
rhage d uring p roctectom y. Arch Surg 1985;120:1015–1020. 54. MacRae H M, McLeod RS, Cohen Z, et al. Risk factors for p elvic p ou ch
27. Dochetry JG, McGregor JR, Akyol AM, et al. Com p arison of m anu ally failu re. Dis Colon Rectum 1997;40:257–262.
constru cted and stap led anastom oses in colorectal su rgery. Ann Surg 55. Breen EM, Schoetz DJ, Marcello PW, et al. Fu nctional resu lts after p er-
1995;221:176–184. ineal com plications of ileal p ou ch-anal anastom osis. Dis Colon Rectum
28. Langevin JM, Rothenberger DA, Gold berg SM. Accid ental sp lenic 1998;41(6):691–695.
inju ry d u ring surgical treatm ent of the colon and rectu m . Surg Gynecol 56. Leon g APK, Lond on o-Sch im m er EE, Phillip s RKS. Life-table an alysis
Obstet 1984;159:139–144. of stom al com p lication s follow ing ileostom y. Br J Surg 1994;81:
29. Fry DE, Milhalen L, H arbeecht R. Iatrogenic ureteral inju ry. Arch Surg 727–729.
1983;118:454. 57. Collett K. Practical aspects of stoma management. Nurs Stand 2002;17(8):
30. McGinty DM, Mend ez R. Trau m atic u reteral inju ries w ith d elayed 45–52.
recognition. Urology 1977;10:115–117. 58. Du chesne JC, Wang YZ, Weintrau b SL, et al. Stom a com p lications: a
31. Bothw ell WN , Bleicher RJ, Dent TL. Prop hylactic u reteral catheteriza- m u ltivariate analysis. Am Surg 2002;68(11):961–966.
tion in colon su rgery: a five-year review. Dis Colon Rectum 1994;37: 59. Bass EM, Del Pino A, Tao A, et al. Does p reop erative stom a m arking
330–334. and ed u cation by the enterostom al therapist affect outcom e? Dis Colon
32. Janu N C, Bokey EL, Chap u is PH , et al. Blad d er d ysfu nction follow ing Rectum 1997;40(4):440–442.
anterior resection for carcinom a of the rectum . Dis Colon Rectum 1986;29: 60. Myers JO, Rothenberger DA. Su gar in the red uction of incarcerated pro-
182–183. lapsed bow el: rep ort of tw o cases. Dis Colon Rectum 1991;34:416–418.
33. Walsh PC, Schlegel PN . Rad ical p elvic su rgery w ith p reservation of 61. William s N S, N asm yth DG, Jones D, et al. Defu nctioning stom as: a
sexu al fu nction. Ann Surg 1988;208:391–400. p rosp ective controlled trial com p aring loop ileostom y w ith loop trans-
34. H ojo K, Saw ad a T, Moriya Y. An analysis of survival and void ing, sex- verse colostom y. Br J Surg 1986;72:566–570.
u al function after w id e iliop elvic lym p had enectom y in p atients w ith 62. Carlsen E, Bergen A. Technical asp ects and com p lication of end
carcinom a of the rectu m , com p ared w ith conventional lym p had enec- ileostom ies. World J Surg 1995;19:632–636.
tom y. Dis Colon Rectum 1989;32:128–133. 63. Abu lafi AM, Sherm an JW, Fid d ian RV. Delorm e op eration for p ro-
35. Lind say I, George B, Kettlew ell M, et al. Rand om ised , d ou ble-blind , lapsed colostom y. Br J Surg 1989;76:1321–1322.
p lacebo-controlled trial of sild enafil (Viagra) for erectile d ysfu nction 64. Shellito PC. Com plications of abd om inal stom a su rgery. Dis Colon Rec-
after rectal excision for cancer and inflam m atory bow el d isease. Dis tum 1998;41(12):1562–1572.
Colon Rectum 2002;45(6):727–732. 65. Doberneck RC. Revision and closu re of the colostom y. Surg Clin North
36. Rasm u ssen OO, Peterson IK, Christianson J. Anorectal fu nction follow - Am 1991;71(1):193–201.
ing low anterior resection. Colorectal Dis 2003;5(3):258–261. 66. Leenan LP, Kyu yp ers JH . Som e factors influ encing the ou tcom e of
37. Ikeu chi H , Kasu noki M, Shoji Y, et al. Clinicop hysiological resu lts after stom a surgery. Dis Colon Rectum 1989;32:500–504.
sp hincter-preserving resection for rectal carcinom a. Int J Colorectal Dis 67. Ru bin MS, Schoetz DJ, Matthew JB. Parastom al hernia: is stom a reloca-
1996;11:172–176. tion su p erior to fascial rep air? Arch Surg 1994;129:413–418.
38. Brasch RC, Bufo AJ, Kreienberg PF, et al. Fem oral neu rop athy second - 68. Balfou r L, Stojkovic SG, Botterill ID, et al. A rand om ized , d ou ble-blind
ary to the use of self-retaining retractor. Rep ort of three cases and trial of the effect of m etronid azole on p ain after closed hem orrhoid ec-
review of the literatu re. Dis Colon Rectum 1995;38:1115–1118. tom y. Dis Colon Rectum 2002;45:1186–1190.
39. Gold m an JA, Feld berg D, Dicker D, et al. Fem oral neu rop athy su bse- 69. Gold stein ET, William son PR, Lach SW. Su bcu taneou s m orp hine p u m p
qu ent to abd om inal hysterectom y: a com p rehensive stu d y. Eur J Obstet for p ostoperative hem orrhoid ectom y p ain m anagem ent. Dis Colon Rec-
Gynecol Reprod Biol 1985;20:385–392. tum 1993;36(5):439–446.
40. Dillavou ED, And erson LR, Bernert RA, et al. Low er extrem ity iatro- 70. Bailey H R, Fergu son JA. Prevention of u rinary retention by flu id
genic nerve inju ry d u e to com p ression d u ring intraabd om inal su rgery. restriction follow ing anorectal op erations. Dis Colon Rectum 1976;19:
Am J Surg 1997;173(6):504–508. 250–252.
41. Sm ith RL, Bohl JK, McElearney ST, et al. Wou nd infection after elective 71. Bled ay R, Pena JP, Rothenberger DA. Sym p tom atic hem orrhoid s, cu r-
colorectal resection. Ann Surg 2004;239(5):599–605. rent incid ence and com p lications of op erative therap y. Dis Colon Rec-
42. Pined a CE, Shelton AA, H ernand ez-Bou ssard T, et al. Mechanical tum 1992;35:477.
bow el preparation in intestinal su rgery: a m eta-analysis and review of 72. Bu ls JG, Gold berg SM. Mod ern m anagem ent of hem orrhoid s. Surg Clin
the literature. Gastrointest Surg 2008;12(11):2037–2044. North Am 1978;58:469–478.
73. Roe AM, Bartolo DCC, Vellacort KD, et al. Su bm u cosal versu s ligation 79. Su ltan AH , Kam m MA, N icholls RJ, et al. Prosp ective stu d y of the
excision hem orrhoid ectom y: a com p arison of anal sensation, anal extent of internal anal sphincter d ivision d uring lateral sphinctero-
sp hincter m anom etry, and p ostop erative p ain and fu nction. Br J Surg tom y. Dis Colon Rectum 1994;37(10):1031–1033.
1987;74:948–951. 80. Garcia G, Su tton C, Mansoori S, et al. Resu lts follow ing conservative
74. Jensen SL. Treatm ent of first ep isod es of acu te anal fissu re: prosp ective lateral sp hincterotom y for the treatm ent of chronic anal fissu res. Col-
rand om ized stu d y of lignocaine ointm ent versu s hyd rocortisone oint- orectal Dis 2003;5:311–314.
m ent or w arm sitz baths p lu s bran. Br Med J 1986;292:1167–1169. 81. Littlejohn DR, N ew stead GL. Tailored lateral sp hincterotom y for anal
75. Lund JN , Arm itage N C, Scholefield JH . Use of glyceryl trinitrate oint- fissu re. Dis Colon Rectum 1997;40(12):1439–1442.
m ent in the treatm ent of anal fissu re. Br J Surg 1996;83:776–777. 82. Chrabot CM, Prasad ML, Abcarian H . Recu rrent anorectal abscesses.
76. Oh C, Divino CM, Steinhagen RM. Anal fissu re: 20-year exp erience. Dis Dis Colon Rectum 1983;24:105–108.
Colon Rectum 1995;38(4):378–382. 83. H u ber J, Kissack AS, Sim onton CT. N ecrotizing soft tissu e infection
77. Rom ano G, Rotond ano G, Santangelo M, et al. A critical ap p raisal of from rectal abscess. Dis Colon Rectum 1983;26:507–511.
pathogenesis and m orbid ity of su rgical treatm ent of chronic anal fis- 84. Lilius H G. Fistula-in-ano, an investigation of hu m an fetal anal d u cts
su re. J Am Coll Surg 1994;178:600–604. and intram u scular gland s and a clinical stu d y of 150 p atients. Acta Chir
78. H iltunen KM, Metikainen M. Closed lateral su bcu taneou s sphinctero- Scand Suppl 1968;383:1–88.
tom y und er local anesthesia in the treatm ent of chronic anal fissure. 85. Joy H , William s JG. The ou tcom e of su rgery for high anal fistu las. Col-
Ann Chir Gynaecol 1991;80:353–356. orectal Dis 2002;4(4):254–261.
CHAPTER
39
Complications of Abdominal
Wall and Hernia Operations
Michael G. Franz
■ COMPLICATIONS OF ABDOMINAL WALL com m on goal has been a safe and efficient operation that
yield s the low est hernia recu rrence rate. The best operation
AND HERNIA SURGERY
is the one tailored to each patient’s u nique problem based
The m ajority of m ajor su rgical p roced u res are p erform ed in on a thorou gh u nd erstand ing of abd om inal w all anatom y
the abd omen or on the abd om inal w all. By d efinition, this and p hysiology and the highest level clinical evid ence.
activity resu lts in inju ry to the abd om inal w all. Rising
Cesarian section rates increases the incid ence of abd om inal
w all com p lications. H ernia repair is the m ost com m on elec- ■ Laparotomy incisions
tive p roced u re in su rgery (1,2). Incisional hernia is the m ost Exposure
com m on com p lication in abd om inal surgery, lead ing to
The id eal laparotom y incision provid es exposu re for the
reoperation (3). Recu rrence is usually recognized as the
safe and effective exam ination and su rgical therapy of
most frequ ent com p lication of hernia rep air. Im p rove-
intraabd om inal organs and stru ctu res. The size of the inci-
m ents in techniqu e have red u ced recu rrence rates follow -
sion is d ictated by the need for a therapeu tic operation and
ing ingu inal hernia repair to 5%. Pain has em erged as the
shou ld not be com p rom ised for cosm etic reasons. The m ain
most frequent com plication follow ing inguinal hernia
p roven benefits follow ing m inim ally invasive proced u res
repair. Recu rrence rem ains the d om inant com plication fol-
are earlier retu rn to u su al activity, low er w ou nd infection
low ing incisional hernia repair. Level 1 stu d ies consistently
rates, less p ain, and less scarring. When an op en techniqu e
find incisional hernia recu rrence rates of 50% follow ing
is ind icated , safe exp osu re shou ld not be com p rom ised to
autologou s tissu e rep airs and 25% w ith the application of
achieve the benefits of m inim ized incisions, since the bene-
a m esh p rosthesis (4,5).
fits usually d o not outw eigh the risk of com p lications asso-
The abd om inal w all is a d ynam ic soft-tissu e stru ctu re
ciated w ith inad equ ate access to d iseased organs.
that fu nctions to m aintain up right posture, allow m ove-
The location of an incision is equal in importance to its
ment of the torso, stabilize the spine, and protect the
size. A misplaced incision of the abdominal w all may com-
enclosed p eritoneal organs. It is com posed of skin, subcu ta-
promise exposure and access. Examples includ e celiotomy
neous tissu es, fascia, m u scles, peritoneum , and associated
incisions placed too high on the abd ominal w all, lead ing to
blood vessels and nerves. H ernias are congenital or iatro-
d ifficulty mobilizing the low er bow el mesenteries and
genic openings in the abd om inal w all that can result in
increasing the risk of ureteral injury, and incisions placed too
the abnorm al m ovem ent of intraabd om in al organs an d
low, increasing the risk of inad vertent injuries to structures
stru ctu res across the d efects. H ernias are clinically d is-
of the upper abdomen, includ ing the bile d uct, esophagus,
abling w hen they becom e p ainfu l or im p air fu n ction of
or spleen. Preoperative imaging studies are useful in plan-
the abd om inal w all. H ernias present as su rgical em ergen-
ning the m ost effective abd ominal w all site for laparotomy.
cies w hen intraabd om inal organs becom e incarcerated or
When using computed tomography scans, the umbilicus
strangu lated w ithin the d efects, lead ing to bow el obstru c-
provid es a useful abd ominal w all surface land mark for
tion and organ infarction. Und erstand ing the pathology of
counting 5- or 10-mm image slices and measuring the opti-
hernias requires a thorough und erstand ing of abd om inal
mum location for incision. Laparotomy incisions extending
w all p hysiology.
to the xiphoid process or pubic symphysis should be
The history of hernia repairs and failures is, in m any
avoid ed . Laparotomy soft-tissue repair is d ifficult in these
w ays, the history of general surgery itself. The era of m od -
locations and can result in incisional herniation.
ern general surgery is fu ll of d escriptions of techniques for
Recom m en d ed abd om inal incision s for sp ecific op er-
the id eal hernia rep air. From the original local au tologou s
ations are d iscu ssed in d ed icated chap ters elsew here.
tissu e reconstru ctions to m od ern alloplastic im plants, the
General p rincip les m ay be ap p lied to all lap arotom y inci-
sions. Mid line celiotom y incisions are u su ally u sed for
Michael G. Franz: University of Michigan, Ann Arbor, MI em ergen cy access an d exp osu re, su ch as follow in g blu nt
48109. or p enetrating trau m a to the abd om en , esp ecially w h en a
500
Chapter 39 • Complications of Abdominal Wall and Hernia Operations 501
d efinitive d iagn osis h as not been m ad e. Th e m id lin e in ci- the abd om en becom es d istend ed p ostop eratively (7). The
sion is the m ost versatile in term s of access to the entire stitch interval m u st therefore elongate w ith the incision; if
p eritoneu m and m ay easily be exten d ed cep halad or cau - the tissu e bite is too sm all, there is an increased chance for
d ad . Elective p roced u res of th e colon and sm all bow el are the su tu re to tear throu gh tissu e. The length of su tu re u sed
also u su ally best p erform ed th rou gh m id line incision s to to close a celiotom y incision has been norm alized to w ou nd
p reserve lateral anterior abd om in al w all integrity in th e length and d efined as a su ture length to w ou nd length ratio
event of a concu rrent or fu tu re ileostom y or colostom y. (SL:WL). The low est w ound d ehiscence rates occurred
The liver, biliary tract, p ancreas, and sp leen are safely using a SL:WL ratio of 4:1, w here one d ehiscence d eveloped
an d com p letely exp osed throu gh bilateral su bcostal in ci- in 1,505 p rosp ective and continuous cases (0.07%). A 1-cm
sions. H ow ever, transverse incisions of the abd om inal stitch interval w ith 1-cm tissue bites achieves the 4:1 SL:WL
w all m ay d evascu larize th e rectu s com p on ents of the ratio (Fig. 39.1). A sim ilar stu d y found that the SL:WL ratio
m id abd om in al w all w hen th e ep igastric arteries are lig- used d u ring closu re of the abd ominal w all at the original
ated . The su bsequ en t atrop hy and fibrosis m ay lead to operation w as also a risk factor for incisional hernia forma-
incisional hernia and m ake later reconstru ction m ore d if- tion. This observation affirms d eveloping theories that the
ficu lt. Most su rgeons ap p ly u p p er m id line incisions for
access and exp osu re of th e stom ach an d intraabd om inal
esop hagu s. Intrathoracic extension of this incision can
im p rove p roxim al exp osu re.
Wound bu rsting strength in cad avers is tw ice as great Wound
for transverse as for m id line incisions w hen su tu res are
Suture
placed 1 cm from the w ound ed ge (6). H ow ever, w hen a
mid line incision is closed using a “w id e-bite” w ith a
throu gh-and -throu gh rectu s m u scle m ass closu re tech-
niqu e, w ou nd bu rsting strength w as 150% to 200% of the
transverse incision closu re. The pred om inant m echanism
of failu re in bu rst-tested cad aver incisions is su tu re cu tting
throu gh tissu e. Retrospective stud ies suggest that the rate
of d ehiscence is higher in m id line incisions than in trans-
verse incisions of the abd om inal w all. Critics of m id line
A
incisions interpret the d ata to show that m id line incisions
are nonanatom ic and cut across aponeurotic fibers, as
op p osed to transverse incisions that cu t p arallel to these 1 cm 1 cm
fibers. Contraction and load ing of the abd om inal w all tend
to p u ll the m id line incision apart, but brings the ed ges of
transverse incisions together. Fu rtherm ore, it is thou ght 1 cm SL = 1 cm + 1 cm
that su tu res in a m id line incision tear ou t m ore easily than WL = 1 cm
in the transverse w ou nd because ripping in the form er X cm
occu rs p arallel to d om inant collagen bu nd les. H ow ever, Celiotomy
incision
available p rosp ective controlled trials have not su bstanti-
ated the belief that transverse incisions su ffer few er d ehis- SL = 2 cm + X cm
cences than m id line incisions. Proponents of the mid line X2 = 4 + 1
laparotom y incision point out that this m ay in p art be d ue X = 2.2 cm
to a negative selection bias in stu d ies of m id line lap aro- SL = 4.2 cm
tom y, w hich are m ost frequently d one in em ergency situ a-
tions, w ith p atients suffering from hypop erfusion (shock)
or sep tic p eritonitis. Both of these clinical scenarios are
know n to im ped e w ound healing and increase w ou nd
com p lications, ind epend ent of the incision type.
Closure
B
Clinical stud ies of acute w ou nd failure report three princi-
FIGURE 39.1. A: Abdominal wall incisions may lengthen by 30% when the
ples of achieving low w ou nd d ehiscence rates: w id e tissu e abdominal wall is loaded for motion or if the abdomen becomes distended
bites, short stitch intervals, and nonstrangu lating tension postoperatively. The ideal stitch interval should elongate with the incision so
on the su tu re. Fu nd am ental to the d evelopm ent of an id eal that the suture does not tear through the fascia. B: The ideal length of suture
to close a celiotomy incision has been normalized to the wound length and
techniqu e of lap arotom y incision closu re is an ap p reciation
defined as the suture length to wound length ratio (SL:WL). The lowest wound
of the fact that the abd ominal w all incision m ay lengthen dehiscence rates occurred using a SL:WL ratio of 4:1. A 1-cm stitch interval
by 30% as a p atient begins to load the abd om inal w all or if with 1-cm tissue bites achieves the 4:1 SL:WL ratio.
majority of incision hernias are d erived from und etected or of abd om inal w all relaxation to com p lete the op tim u m clo-
occult fascial d ehiscences. The prepond erance of d ata su p - su re. Prosp ective stu d ies of abd om inal w all closu re tech-
ports the u se of a ru nning, mass closure w ith a SL:WL ratio niqu es su ggest that the op tim u m d ep th of a fascial stitch is
of 4:1 or greater (6). 1 cm into norm al fascia (7). Deep er fascial stitches, su ch as
Su tu re tension that raises the interstitial p ressu re in the those p laced as retention su tu res, increase the risk of bow el
center of the incision above capillary perfu sion pressu re (30 inju ry. Distend ed organs also increase the risk for injury.
to 40 m m H g) m ay cau se fascial necrosis. In anim al stu d ies,
this situ ation has increased the risk of acu te w ou nd failu re. Retained Instrument
Id eal su tu re tension shou ld ap p roxim ate fascia w hile m ain- A retained instru ment, sp onge, or need le is a technical
taining the p erfu sion of healing tissue. A short, 1-cm stitch error that can occu r d u ring lap arotom y. The com plication
interval w ith a m od erate tension load shou ld prevent occu rs m ost often d u ring em ergency p roced u res or w hen
om entu m or intestine from p rotru d ing throu gh the su tu re op erating in tw o or m ore w id ely sep arated field s and w hen
line. u sing p acks for hem ostasis (11). Retained gau ze cau ses
abscess form ation. Retained instru m ents or need les m ay
Unplanned Visceral Injury p enetrate viscera and cau se an abscess, fistu la, or obstruc-
Abd om inal organs m ay be inju red w hen the p eritoneu m is tion. The retention of need les is best avoid ed by the com -
op ened . The risk of visceral inju ry d u ring lap arotom y is p ulsive reapp lication of need les to need le d rivers and by
increased by the p resence of p reviou s abd om inal w all accou nting for every need le w hen an em p ty d river is
scars, ad hesions, and d istend ed organs. The risk of vis- retu rned . In m ost hosp itals, all instru m ents and need les are
ceral inju ry can be red u ced by incising the abd om inal w all cou nted .
in layers, carefu lly id entifying com p onent stru ctu res and The incid ence of retained gauze sponges may be reduced
layers, retracting as need ed , and id entifying the p eri- w hen restricted to using only large laparotomy pads when
toneu m . In the p resence of d ense scars or ad hesions, sharp operating in the abdomen. Sponge stick or peanut d issec-
d issection is u su ally recom m end ed u ntil p otential p lanes tors shou ld be avoid ed . Large gau ze p ad s are m ore easily
betw een organs and the p eritoneum are id entified . This p alpated d u ring a careful m anual search of the peritoneal
may avoid uncontrolled heat injury from electrocau tery. cavity. The su rgeons shou ld vigilantly accou nt for the
Often, a lateral d issection m u st be p ursued aw ay from the p lacem ent and rem oval of all lap arotom y p ad s. Su rgeons
mid line scar u ntil the uninju red peritoneum is id entified should rou tinely exam ine all locations w here gau ze pad s
and more safely and easily op ened . The introd uction of m ight have been p laced , su ch as behind the liver or spleen.
synthetic m esh p rostheses to rep air incisional ventral her- The nu rsing sp onge cou nt need s to be correct. An incom -
nias has led to an increased incid ence of unplanned bow el p lete closing cou nt requires a reexam ination of the peri-
injury and bow el resection d u ring a later abd om inal opera- toneal cavity and retrieval of the m issing sp onge. If the
tion (8,9). This is a significant d evelopm ent in the safety of final cou nt rem ains incom p lete, an intraop erative rad i-
mesh p rostheses, since som e estim ate that at least 12% of ograp h shou ld be p erform ed to p rove w ithou t any d ou bt
all abd om inal su rgery patients w ill be reoperated in their that no rad iopaque m arker rem ains in the abd om en.
lifetim e, w ith 25% of incisional hernia patients rep aired Desp ite system atic ap p roaches and a correct cou nt, a
w ith a synthetic m esh (3,10). gau ze p ad or even an instru m ent m ight be left. If this situ a-
Retractors m ay also cau se u nintend ed organ inju ry. tion is d etected in the p ostop erative p eriod , the surgeon
Great vigilance m u st be u sed in the safe ap p lication of shou ld first inform the p atient or the p atient’s fam ily, or
hand held and self-retaining abd om inal retractors. In a nor- both, of the p resence of the foreign bod y and then recom -
mal p eritoneu m , each retractor should be placed u nd er m end its rem oval at the safest interval.
d irect vision and the d eep ed ge palpated to ensu re safe
placem ent w ithou t u nd ue tension on organs. In a reop era- Incisional Pain
tive peritoneu m w ith d ense ad hesions, great care m u st be Clinical exp erience su ggests that som e abd om inal w all
used to p revent torqu e injuries caused by retractors p u lling incisions are m ore p ainfu l than others in the p eriop erative
on ad hered stru ctu res. Follow ing rem oval of retractors, p eriod . Method s for m easu ring incisional p ain inclu d e the
abd om inal organs should rou tinely be examined for inju ry. u se of pain analog scales and narcotic analgesic requ ire-
Retractor injury is not alw ays obvious at the tim e of m ents. Resp iratory sp linting d u e to abd om inal w all inci-
abd om inal w all closure, and the first sign of injury m ay be sional p ain and narcotic therapy both pred ispose to
d elayed hem orrhage or intestinal perforation d u ring the red u ced p u lmonary tid al volu m es and atelectasis. Urinary
convalescent p eriod . retention and d elayed gastrointestinal function m ay also
Su tu res m ay p enetrate the intestines d u ring closu re of follow increased narcotic u sage d u e to abd om inal w all
the abd om inal w all and can resu lt in bow el obstru ction and p ain. It is generally believed that p ain is greatest follow ing
fistu lization. This is m ost easily avoid ed by m aintaining vertical m id line and param ed ian incisions becau se they are
carefu l anatom ic id entification of abd om inal w all and vis- subject to the greatest d istractive forces d uring recovery.
ceral stru ctu res at the end of the case. Com m unication w ith Abd om inal w all flexion and extension and lateral traction
the anesthesiologist is help fu l to m aintain ad equ ate levels from the obliqu e m u scu latu re are the p rim ary sou rces of
vertical lap arotom y w ound m otion. Less pain is rep orted m ay incorp orate into the abd om inal w all better and be
follow ing transverse and obliqu e abd om inal w all incisions, m ore likely to clear a m esh-associated infection.
esp ecially retrop eritoneal flank incisions. In these incisions, Another approach to temporary closure of infected
the norm al abd om inal w all load forces are d istribu ted p ar- and/ or contaminated abd ominal wall defects has been the
allel to the abd om inal w all w ound s, thereby m inim izing use of absorbable implants such as polyglycolic acid poly-
d istractive w ou nd -load vectors. Many su rgeons believe mer mesh. These materials may also fistulize to bow el and
that a transverse incision m inim izes resp iratory d ysfu nc- alw ays result in a large incisional hernia that presents a set of
tion in p atients w ith p ulmonary d isease. A d efinitive stu d y significant second ary surgical problems and complications.
of p ain associated w ith abd om inal w all incisions is d ifficu lt Large series and a grow ing experience d emonstrate the suc-
to control and has not been d one. cessful management of infected or contaminated abd ominal
w all d efects using collagen-based biological soft-tissue
Abdominal Wall Wound Infections implants (12–14). Biological mesh sheets are derived from
Abdominal wall w ound infections may be categorized as porcine dermis, porcine submucosa (xenografts), or cad av-
superficial, deep, or organ space, depending on the anatomic eric dermis (allografts) follow ing the removal of all cells. Ide-
location of the infected wounded tissue. Most serious are ally, biological meshes act as an extracellular matrix scaffold.
deep laparotom y wound infections. The best-characterized The grafts are repopulated w ith host abd ominal wall cells
invasive organisms include hemolytic streptococci, staphy- like repair fibroblasts and become vascularized so that
lococci, clostrid ia, and synergistic combinations of gram- w ound infections may clear and long-term abd ominal w all
negative rods and anaerobes (streptococci or bacteroides). w ound mechanical integrity is maintained . Prospective, ran-
The invasive infections frequently cause intense pain and d omized stud ies are required to d etermine the safety and
tend erness. Patients d eveloping these signs and symptoms efficacy of new er abdominal w all implants.
as early as the second postoperative day must be follow ed Most abd om inal w all w ou nd infections are confined to
closely for p rogression to abd om inal w all crep itu s and the su bcu taneou s fat as cellu litis. There infections m anifest
signs of toxem ia. The p rim ary therap y for abd om inal w all as increasing w ou nd p ain and tend erness on p ostoperative
w ou nd infections is to op en the w ou nd , begin m oist d ress- d ays 5 to 7 w hen a norm al w ou nd inflam m atory response
ing changes, and allow healing by second ary intent. shou ld be resolving. Su bcu taneou s tissu e necrosis also pre-
Gram -p ositive cellu litis m ay resp ond to -lactam antibi- d isp oses to abscess form ation follow ing cau tery, m ass liga-
otics. All other invasive infections requ ire u rgent su rgical tu re, or creation of ischem ic su tu re lines. The incid ence of
d ebrid em ent of d estroyed tissue and intravenous antibiotics su bcu taneou s abscesses ap p ears to be higher in obese
directed toward the offending organism or organisms. Resis- p atients.
tant Staphylococcus aureus is increasingly the cause of w ound Once d iagnosed , esp ecially in the p resence of fever and
infection follow ing hernia repair, especially in the presence an elevated w hite blood cell cou nt, a su p erficial w ou nd
of a synthetic mesh implant. Repeated d ebrid ements may be shou ld be op ened throu gh the skin and all p u s shou ld be
required until the infection is controlled, including mesh d rained . Antibiotics are u su ally not necessary u nless the
explantation. abscess is associated w ith an invasive soft-tissu e infection
Debrid em ent of abd om inal w all infections m ay resu lt or an ad jacent p rosthesis, or both. These w ou nd s shou ld be
in fu ll-thickness d efects exp osing the p eritoneu m . These lightly packed w ith m oistened gau ze tw o to three tim es a
are d ifficult su rgical circu m stances requ iring a variety of d ay u ntil norm al granu lation tissu e ap p ears and w ou nd
approaches to effect su ccessfu l abd ominal w all w ou nd contraction begins.
management. Trad itionally, a temporary alloplastic im plant Mu ltifilam ent, nonabsorbable su tu res m ay harbor bac-
like polypropylene mesh has been used to brid ge the teria and p red isp ose a w ou nd to stitch abscess and sinu ses.
m yofascial d efect. Allop lastic m aterials m ay, how ever, A recu rrent stitch abscess d iagnosed m onths or years after
behave as foreign bod ies w ithin a contam inated field and an op eration shou ld be treated by excision of the offend ing
becom e chronically infected . In ad d ition, a high incid ence stitch. Waiting m ay resu lt in sp ontaneou s exp ulsion of the
of bow el fistu lization has been rep orted u sing m eshed allo- stitch, or the w ou nd m ay be op eratively reexplored u nd er
plastics. It is id eal if a large om entum or existing p rep eri- controlled cond itions.
toneal tissu e p rotects p eritoneal organs before allop lastic
im p lantation of a contam inated or infected field . Microp -
orou s allop lastics like extru d ed p olytetraflu oroethylene
■ Myofascial dehiscence and evisceration
(ePTFE) have also been successfully u sed for serial tem po- The reported incid ence of fascial d ehiscence (acu te laparo-
rary closu re of the abd om inal w all. This approach involves tom y w ou nd failu re) ranges from 0.2% to 10% (4,6). The
intensive care unit level sed ation or a retu rn to the operat- Veterans Affairs N ational Su rgical Qu ality Im p rovem ent
ing room every 2 to 3 d ays for w ou nd d ebrid em ent and Program (N SQIP) m aintains the largest prospective d ata-
“reefing” of the alloplastic brid ge closu re to red u ce the base of perioperative su rgical risk factors and ou tcom es in
implant surface area. Ultimately, closure w ith au tologous the United States (15). An analysis of 34,809 laparotom ies
ventral abd ominal w all myofascia is achieved . N ew er, p erform ed betw een 1996 and 2000 revealed a 3.3% inci-
lighter-w eight and larger pore size synthetic m esh im p lants d ence of fascial d ehiscence. This rate is in agreem ent w ith
the Eu rop ean exp erience and the Du tch H ernia Registry w ith gentle m oist irrigation and nonad herent d ressings
(3% to 5%) (16). A review of the fascial d ehiscence literatu re u ntil covered w ith granu lation tissu e. Ep id erm al closure
show s that the rates of rep orted fascial d ehiscence are m ay be accelerated w ith a sp lit-thickness skin graft if nec-
higher in prospective stu d ies than in retrospective review s. essary. An incisional hernia is inevitable w ith this approach
It ap p ears that obesity increases the rate of acu te d ehis- and w ill p resent a set of su rgical p roblem s at a later d ate.
cence, most likely to increased load forces on the su tu re line When the d efect is large enou gh to threaten evisceration,
(17). Exp ert consensu s is that the m ost com m on m echa- the acu te abd om inal d efect m ay require m echanical rein-
nism for acu te fascial d ehiscence is a technical error in forcem ent or rep lacem ent w ith an ap p rop riate im p lant.
sutu re line p lacem ent. This m ost frequ ently is the resu lt of In the p resence of abd om inal infection, m any su rgeons
inad equ ate closu re at the end s of the su tu re line, too tight u se absorbable m aterial like polyglycolic acid polym er
sutu re line closu re, and w ou nd ischem ia or suture p u ll- m esh. This ap p roach w ill also resu lt in the certain d evelop-
throu gh. In the Veterans Ad m inistration N SQIP stu d y, m ent of a ventral incisional hernia, bu t it is less likely to
d eep w ou nd sp ace infection w as the greatest risk factor for cau se a chronic, foreign bod y abscess. In very large ventral
fascial d ehiscence. It is probable that som e cases of d eep d efects, rap id ly absorbable m eshes m ay m echanically fail
sp ace infections follow ing lap arotom y are d erived from 2 to 3 w eeks after im p lantation, p lacing ad herent bow el at
apparent or evolving gastrointestinal fistu las. Other signif- risk for shear inju ries lead ing to enterotom y and fistu liza-
icant perioperative risk factors includ ed failu re to w ean tion. Polypropylene w oven m esh im plants m aintain greater
from the ventilator and em ergency proced u res. breaking and tensile strength bu t have an increased risk
Acute m yofascial w ound failure occurs for one of fou r of m esh infection and d elayed bow el inju ry. Both p olygly-
fu nd am ental reasons: a su tu re breaks, a knot u nties, a loose colic acid p olym er and p olyp rop ylene m esh are associ-
or excessive stitch interval that allow s the p rotru sion of vis- ated w ith a risk for fistu lization to the bow el (8,9). Every
cera, or su tu re p u lls through the fascia. Contemp orary d ata effort shou ld therefore be m ad e to interpose om entu m or
su ggest that tissu e tearing is the p red om inant cau se of p rep eritoneal fat betw een the m esh im p lants and viscera.
d ehiscence and that in the absence of recognized risk fac- N ew er reinforcing im p lants d erived from collagen-based
tors the p rim ary m echanism is an inad equ ate tissu e bite biological sou rces like p orcine d erm is, p orcine su bm ucosa,
w ith the su tu re need le (6). or cad averic d erm is m ay p rovid e an effective alternative.
Myofascial d ehiscence or the mechanical separation of The anticip ated m echanism of action w ith biological m esh
coapted fascial w ound ed ges follow s tw o major scenarios. im plants is to p rovid e the m echanical stability of a syn-
The first form of fascial d ehiscence occurs w ithout a w ound thetic im p lant w hile avoid ing the risk of chronic foreign
infection. The classic clinical find ing is the su d d en soaking bod y–ind u ced inflam m ation and infection. ePTFE m esh
of d ressings and sheets w ith serosanguineous fluid on post- p atches are microp orou s on the p eritoneal su rface, possibly
operative d ays 3 to 7. This sign is reported to occur in 23% to resu lting in low er visceral ad hesions and fistu las. This
84% of cases of d ocumented d ehiscence (6). Patients w ill sam e microm echanical d esign, how ever, lim its both fibrob-
report a “gush” of “w atermelon”-colored fluid . When the last and inflam m atory cell ingrow th and resu lts in a
area of the d ehiscence is small, evisceration may not occu r slightly greater risk for im p lant associated infections. PTFE
as the inflamed viscera ad here to each other and to the pari- p robably shou ld not be u sed for p erm anent rep air in the
etal peritoneu m . When fascial d ehiscence is su spected in setting of acu te d ehiscence, given the contam inated nature
the early postoperative period , the patient should urgently of these w ou nd s.
be sent back to the operating room for reclosure. Many series rep ort m ortality rates of 15% to 50% fol-
It is also now known that most fascial dehiscences are low ing d ehiscence and evisceration (19). It is not clear if
occult, remaining clinically undetected. One study found that this alarm ingly high m ortality is the resu lt of the clinical
94% of incisional hernias resulted from clinically occult fas- risk factors lead ing to d ehiscence, the su rgical and m ed ical
cial dehiscences of laparotomy wounds that had occurred as interventions requ ired follow ing d ehiscence, or a com bina-
early as postoperative day 30. The mechanically intact over- tion of both. Too often, d ehiscences associated w ith d eep
lying skin wound prevented earlier d iagnosis. In larger area sp ace w ou nd infections are not clearly sep arated from
dehiscences, small bowel and omentum may cross the those occu rring in the absence of an infection. Another fre-
myofascial closure and be visibly apparent (16,18). qu ent criticism of stu d ies of fascial d ehiscence is that they
The second m ost frequ ently encou ntered scenario inclu d e large nu m bers of p atients at extrem ely low risk for
involves m yofascial infection in the d eep w ou nd sp ace. acu te fascial w ou nd failu re.
The associated tissu e inflam m ation and necrosis p red is- The m ost frequ ently rep orted system ic risk factors for
pose to fascial failu re and the “pulling through” of su tu res acu te fascial w ou nd failu re inclu d e severe m alnu trition,
and w ou nd ed ge sep aration. In this circu mstance, the shock, obesity, u rem ia, and liver failu re. Local w ou nd fac-
w ound infection m ust be treated w ith ad d ed caution d u e tors inclu d e m echanical load ing of the abd om inal w all
to the anatom ic d efect. There is an increased risk for entero- d u e to ileu s or m echanical ventilation, ascites, and d eep
cu taneous fistulas w hen d ebrid ing necrotic tissue in the w ou nd infection (6). There is no p roof that m id line lap aro-
d eep sp ace of an infected celiotom y w ou nd . When clini- tom y incisions are m ore likely to resu lt in evisceration
cally ap p rop riate, a sm all area d ehiscence m ay be m anaged than transverse or oblique incisions. As alread y mentioned ,
Table 3 9 .1 Risk fa ct ors for m yofa scia l d eh iscen ce Acute serosanguinous wound fluid
Systemic Local
Malnutrition Abdominal distention from ileus
Shock Prolonged ventilation Earlier than postoperative day 7
Obesity Deep wound infection

Steroids and antiproliferative drugs Ascites No
Operative candidate
Uremia Poor surgical technique Yes No
Liver failure Ischemia
Immediate operative reclosure Rule out bowel
Age 65 Ostomy near incision incarceration or
Malignancy strangulation
Moist dressing
the best p rosp ective stu d ies of acu te abd om inal w all
changes
w ou nd failu re note that m id line celiotom y incisions are
m ore likely to be u sed in m u ltip ly inju red , sep tic, or can- FIGURE 39.2. If fascial dehiscence is suspected, most patients should be
cer p atients. returned to the operating room for careful wound examination and immediate
reclosure. Bedside probing does not have the sensitivity or specificity to diag-
Scoring systems used to predict acute w ound failure have nose fascial dehiscence. If the patient is not a candidate for operative inter-
focused on patient characteristics. One case–control study vention, frequent moist dressing changes with nonadherent dressings may be
empirically documented risk factors associated with fascial used, accepting the inevitability of an incisional hernia. When the nonopera-
tive path is chosen, it must be confirmed that there is no incarceration,
dehiscence as follow s: Age 65, w ou nd infection, p u l-
obstruction, or strangulation of bowel.
monary disease, hemodynamic instability, ostomy within the
incision, low serum albumin, sepsis, obesity, uremia, hyper-
alimentation, malignancy, ascites, steroid use, and hyperten- ap p lied alternative is the techniqu e of p lacing interru pted
sion. Patients with three to five of these characteristics were at internal retention sutures d uring the continu ou s closure of
a significantly increased risk for acute w ound failure. All a celiotom y incision, althou gh no d efinitive outcom es d ata
patients w ith eight or more characteristics d eveloped dis- are available.
rupted wounds (Table 39.1) (10). If d ehiscence is clinically su sp ected based on the su d -
The u se of long-acting absorbable versu s p erm anent d en ap p earance of serosangu ineou s flu id on d ressings in
su tu re m aterial has never been show n to affect w ou nd the early p ostop erative p eriod , p atients shou ld be sent
d ehiscence rates. Sim ilarly, it has not been d efinitively back to the op erating room for carefu l w ou nd exam ina-
show n that u sing continu ou s versu s interru p ted tech- tion and im m ed iate reclosu re. Bed sid e p robing d oes not
niqu e affects the incid ence of d ehiscence (6). One large have the sensitivity or sp ecificity need ed to d iagnose fas-
p rosp ective series d id rep ort that the u se of a continu ou s cial d ehiscence. If the p atient is not a cand id ate for op era-
su tu ring techniqu e w ith an SL:WL ratio of 4:1 resu lted in tive intervention, frequ ent m oist d ressing changes w ith
the low est incid ence of incisional hernia form ation over a nonad herent d ressings m ay be em p loyed , accep ting the
10-year follow -u p p eriod (7). This closu re is achieved by evolu tion of an incisional hernia. If the nonop erative p ath
taking a 1-cm bite back from the fascial ed ge and m aking is chosen, it m u st be confirm ed that there is no incarcera-
1 cm of p rogress w ith each stitch. The id eal continu ou s tion, obstru ction, or strangu lation of bow el (Fig. 39.2).
su tu re length resu lts in a coil arou nd the fascial closu re Rem arkably, the resu lts of reclosu re are u su ally good . It is
that exp and s w ith the w ou nd as the p atient recovers. This likely that healing of the second closu re is accelerated d u e
coil m inim izes high load s at the fascial-stitch interface, to the p resence in the second w ou nd of the cellu lar and
d ecreasing the incid ence of su tu res “p u lling throu gh” m olecu lar elem ents of tissu e rep air. Classic w ou nd stu d -
(Fig. 39.1). The only obviou s d isad vantage of the continu - ies show ed long ago that d elayed reclosu re of incisions
ou s su tu re techniqu e is that if the single su tu re fails, the resu lts in the accelerated recovery of w ou nd tensile
entire w ou nd is at risk. strength (20,21).
Som e su rgeons u se retention su tu res p assing throu gh
all layers of the abd om inal w all to prevent evisceration of ■ Preoperative risk factors for abdominal
patients at increased risk for d ehiscence. Available series
wall and hernia operations
find that this technique m ay p revent clinically d isastrou s
evisceration, bu t d oes not low er the incid ence of fascial Prospective, rand omized controlled trials of hernia opera-
d ehiscence or incisional hernia formation. Most su rgeons tions d escribe both mechanical and biological preoperative
believe that the ischemic and traumatic effects of external risk factors for hernia recurrence following repair. A level 1
retention sutures on the skin outw eigh the limited effect on study of incisional hernia repair found that recurrent hernia-
outcomes of high-risk abd ominal w all closures. A frequ ently tion w ithin 3 years of the operation w as significantly more
likely to occur in men w ith symptoms of prostatism or blad- The w ou nd infection rate ap p ears to be higher follow -
der outlet obstruction and in patients with a history of an ing abd om inal w all hernia repair than for other clean cases,
abd ominal aortic aneurysm (4,5). Presumably, prostatism althou gh the m echanism is u nclear (25,26). One p ossibility
contributes to the higher rate of hernia recurrence because of is that patients w ith significant com orbid cond itions are at
repetitive Valsalva maneuvers or loading of the repaired risk for both hernia form ation and w ou nd infection. A Vet-
abd ominal w all that occurs with urination. Patients who erans Ad m inistration N SQIP stu d y fou nd a 4.3% w ou nd
develop abd ominal aortic aneurysms express abnormal tis- infection rate and 15.1% hernia recu rrence rate. Another
sue collagen isoforms and m etalloproteinase levels. The stu d y rep orted a 16% w ou nd infection rate follow ing inci-
aberrant structural collagen and increased turnover cat- sional ventral hernia rep air (26). The exp ected clean surgi-
alyzed by tissue proteinases result in defective w ound repair cal w ou nd infection rate for nonhernia cases is closer to 1%.
(22,23). Mu ltip le logistic and linear regression analyses have d ocu-
Another established risk factor for recurrent herniation is m ented that coronary artery d isease, chronic obstructive
operating upon an alread y recurrent hernia. The incid ence p u lm onary d isease, low seru m albu m in, and steroid u se
of recurrent herniation follow ing repair increases w ith each are ind ep end ent risk factors for w ou nd infection and pro-
subsequent repair (3). A prospective, rand omized , con- longed hospital stay.
trolled trial of incisional hernia repair established a 24%
recurrence rate w ith the use of a polypropylene synthetic
mesh implant and a 54% recurrence rate follow ing a primary
■ Modification of preoperative risk factors
repair using in situ local autologous tissues after the initial On the basis of p rosp ective, rand om ized , controlled trials
hernia repair (4,5). Many less w ell- controlled studies and of hernia rep air, it is p ru d ent to screen p rosp ective hernia
large clinical experiences report hernia recurrence rate of rep air p atients for signs and symp tom s of p rostatism (4,5).
50% after the second hernia repair and 60% after the third. By logical extension, qu estions shou ld be asked d u ring the
Preclinical wound healing data suggest that part of the p reoperative evaluation abou t other sym p toms lead ing to
explanation for increased recurrent hernia rates follow ing chronic Valsalva m aneu vers or load ing of the abd om inal
each repair is the selection of a d efective, chronic w ound. w all. Increased d ifficu lties having bow el m ovem ents or a
Since incisional hernias are iatrogenic, they are associ- chronic cou gh are com m on exam p les. Im p ortant colorectal
ated w ith a u niqu e set of p reoperative risk factors. It w as p athology is often d iagnosed d u ring w orku ps for hernias.
long held in the surgical w ound healing literature that inci- When tim e p ermits, a u rologic or gastrointestinal evalu a-
sional hernias w ere a late event, d eveloping years after tion m ay be ind icated p rior to hernia su rgery to d iagnose
celiotom y closu re. Sm all series and class II d ata su ggested and treat occu lt p rocesses and to p otentially im prove the
that abnorm al p rogression throu gh all the p hases of w ou nd results of rep air.
healing (inflam m ation, fibrop lasia, and scar m aturation) Most biological risk factors are m ore d ifficu lt to cor-
ultim ately resu lted in w ound breakd ow n and herniation rect. Clearly, w hen there is an infection of the abd om inal
(24). Biochem ical m easu rem ents suggested d efects in colla- w all, all effort m u st be m ad e to red u ce bacterial biobu r-
gen isoform structure and tissue proteinase expression as a d en p rior to rep air or reconstru ction. Com m on clinical
late p henom enon. scenarios are an existing m esh infection or associated
A more recent and provocative hypothesis suggests that enterocu taneou s fistu la. Patients w ith abd om inal aortic
most incisional hernias occur as the result of very early aneu rysm s exp ress d efective tissu e rep air p athw ays that
occult abd ominal w all w ound d ehiscence (16,18). Prospec- cannot be treated tod ay (27,28). Op erating d u ring p eriod s
tively, at the time of celiotomy closure in 149 patients, metal of p rofou nd shock is often u navoid able w hen a life is at
clips w ere placed along the bord er of the myofascial incision stake. All efforts shou ld be d irected tow ard correcting
and the skin closed as usual. Plain film abdominal x-rays hem od ynam ics and u sing op tim u m su rgical techniqu e.
w ere then performed on postoperative d ay 30. Eighteen Cessation of cigarette sm oking has been show n to
(12%) of the patients d eveloped clinically obvious incisional im p rove skin healing, bu t it is not clear that cessation
hernias during the 43-month follow -up, as demonstrated by affects rates of abd om inal w all w ou nd failu re (29). It is
separation of the metallic markers on postoperative x-ray. Of likely that cigarette sm oking im p ed es tissu e rep air p ath-
the 18 patients w ho d eveloped incisional hernias, 17 (94%) w ays d ep end ent on oxygen d elivery and that associated
demonstrated 12 mm or greater fascial clip separation by chronic cou ghs overload abd om inal w all closu re. Obesity
postoperative d ay 30. By contrast, only one of the remaining has never been show n to cau se a w ou nd healing d efect.
131 patients w ho did not develop 12-mm fascial separation H ow ever, increased m echanical forces are likely to con-
by postoperative day 30 d eveloped a hernia. This simple, tribu te to abd om inal w all w ou nd failu re. Class I d ata
but well-done study indicates a much higher rate of occult show an increased incid ence of incisional hernia form a-
primary celiotomy wound failure—in the vicinity of 11% to tion in obese p atients (17). Efforts to lose w eight p rior to
15%. The high incidence appears to be due to the lag phase hernia rep air su rgery shou ld im p rove ou tcom es, althou gh
in the recovery of w ound tensile strength follow ing injury. It this belief has never been d efinitively p roven. Red uced
appears that obesity increases this already high baseline rate w eight red uces fascial w ound load forces and also pro-
of primary fascial d ehiscence (17). vid es locally m obile skin to assu re fascial w ound coverage.
External oblique
muscle
Internal oblique
muscle
Transversus
abdominis muscle
Inferior epigastric
vessels
Transversalis
fascia
Spermatic cord
External
HR
inguinal ring
Fis
ch
er
4'0
FIGURE 39.3. Normal anatomy of the left inguinal canal.
Inguinal Hernias herniate. Although proponents of each technique report very

low personal recurrence rates, prospectively controlled series
Inguinal hernia repair is the most common abdominal wall report recurrence rates of 6% to 11% w hen general surgeons
operation and the most frequent elective procedure per- use these techniques outsid e of dedicated centers (31).
formed by general surgeons (Fig. 39.3). Comparing the The p osterior w all of the ingu inal canal is com p osed of
results of d ifferent operative approaches to hernia repair is the transversalis m u scle, its ap oneu rosis, and the trans-
difficult. There is no agreed-upon definition of hernia recur- versalis fascia that together insert on Coop er ligam ent. In
rence, typically the most cited outcome measure. Most hernia the inferior abd om inal w all, there is a w eak area in the
surgeons support the appearance of any new hernia on the groin w here overlying m yofascia d o not reinforce this
operative side as the definition of a recurrence. Distinguish- p osterior layer. This area of the p osterior, inferior abd om -
ing a new hernia from a recurrent hernia through an existing inal w all is often referred to as the m yop ectineal orifice.
repair is often inexact. The other possibility is that an adjacent The area is d efined by the rectu s m u scle m ed ially, the
defect w ent undetected and a persistent hernia manifests in internal obliqu e and transversalis m u scles su p eriorly,
the postoperative period. The length of follow -up also affects the iliopsoas muscle laterally, and the pubis inferiorly. The
the quality of hernia repair outcome databases. Recurrence myopectineal orifice is crossed by the inguinal ligament and
rates increase with increased length of follow-up. Recurrence traversed by the spermatic cord and femoral vessels. All
rates also increase when dedicated, expert postoperative groin hernias begin as w eaknesses w ithin the myopectineal
examinations are used for assessment (30). orifice. The transversalis fascia d eteriorates, resulting in
The original operations designed for inguinal hernia peritoneal protrusion. Inguinal hernias are surgically treated
repair all depended on locoregional tissue transfers, usually by repairing all or part of the myopectineal orifice directly
based on repairing and reinforcing the posterior w all of the using autologous tissue or by implanting a prosthesis to
inguinal canal, or the transversalis muscle and fascia (Bassini augment or replace the defective transversalis fascia.
and Should ice repairs). The ad vantages of these approaches A method of classifying inguinal hernias helps to stan-
include simple operations w ithout the need for prostheses d ard ize the operations performed and to quantify surgical
and the reliable healing of well-vascularized tissues. The outcomes. One frequently used classification system for
problems associated with local tissue repairs include biome- inguinal hernias w as devised by Nyhus (Table 39.2). Type I
chanical limitations (closing “und er tension”) and the use of inguinal hernias occur most commonly in infants and chil-
abnorm al tissue that alread y d em onstrates a tend ency to d ren w here the internal ring is normal in size and structure
Table 3 9 .2 N yh u s cla ssifi ca t ion of op eration s. Th e resu lts of the Sh ou ld ice techn iqu e are
in gu in a l h er n ia s also w id ely rep orted in th e su rgical literatu re and m ain -
tained in a large d atabase. As p erform ed at The Shou ld ice
Type I indirect inguinal hernia Clinic, the Shou ld ice rep air p rom otes an integrated con-
Internal ring is normal cep t of hernia su rgery that inclu d es p reop erative p rep ara-
Type II indirect inguinal hernia tion and ed u cation, an extensive ingu inal floor d issection,
Internal ring is dilated, but the posterior inguinal wall is intact and closely su p ervised early p ostop erative convalescence.
Type III posterior inguinal wall defects It is generally consid ered a com p lex technical op eration,
Direct inguinal hernia w ith w id e variation in resu lts rep orted . The Shou ld ice
Indirect inguinal hernia with dilated internal ring and attenuated Clinic itself continu es to rep ort long-term total h ernia
medial transversalis fascia of the Hesselbach triangle recu rren ce rates of 1% (31). Th ese ou tstan d in g resu lts are
Femoral hernias rarely d u p licated ou tsid e of the Shou ld ice Clinic or in a
Type IVrecurrent inguinal hernias controlled and p ow ered , p rosp ective, rand om ized trial of
Direct ingu inal hernia rep air.
Indirect Shou ld ice p ioneered early p ostop erative am bu lation
Femoral w ithout increased com plications, a fund am ental principle of
Combined mod ern surgery. H ospital stays follow ing inguinal hernior-
rhaphy w ere reduced from 21 to 3 days. General or spinal
anesthetics were converted to local infiltration of anesthetic
to promote earlier ambulation and return to usual activity.
and the Hesselbach triangle is normal as well. The mecha- Fine silk su tu res w ere fou nd to be associated w ith an
nism of herniation is a patent processus vaginalis of variable increased risk of suture abscess and were exchanged for less
length from the internal ring. Type II inguinal hernias are reactive monofilaments like fine w ire, and now polypropy-
indirect defects where the internal ring is now enlarged with lene or PDS. Groin wound infection rates were also reduced
some impingement on the d eep inferior epigastric vessels by staging bilateral inguinal hernia repairs 2 days apart,
but without d efects within the Hesselbach triangle. Exami- w hich also facilitates the use of local anesthetics.
nation of the inguinal canal’s med ial floor may be performed The su ccessfu l m u ltifaceted ap p roach of the Shou ld ice
through the d ilated internal ring, confirming its integrity. Clinic and the Shou ld ice techniqu e m ay be extend ed to all
Type III inguinal hernias involve d efects in the posterior w all typ es of m anagem ent for ingu inal hernias. In ad d ition to
(floor) of the inguinal canal and have been classified into an op en techniqu e u sing local anesthetics and encou rag-
three subtypes: d irect, ind irect, and femoral. Type IIIA ing early am bu lation, the Shou ld ice Clinic ap p lies other
defects are d irect inguinal hernias without protrusion general p rincip les to its m anagem ent of ingu inal hernias.
through the internal ring. Type IIIB d efects are ind irect and Weight red u ction is a frequ ently overlooked p reop erative
occur through a much-d ilated internal ring w ith significant p rep aration that m ay m ake hernia rep air technically m ore
impingement and deterioration of the inguinal floor medial su ccessfu l. Most series of herniorrhap hy ou tcom es now
to the inferior epigastric vessels w ith or w ithout a scrotal show that increased w eight increases the risk of hernia
component to the hernia. The d istortion of the internal ring recu rrence. Weight loss im p roves the effectiveness of the
may occur w ithout d isplacement of the inferior epigastric local anesthetic techniqu e and im p roves anatom ic d issec-
vessels. The hernia may have both direct and indirect com- tions for bilateral and recu rrent hernias. They also believe
ponents, resulting in a pantaloon hernia surrounding the that the p ostop erative load p laced across the rep air is
inferior epigastric vessels. Femoral hernias are classified as m ore cond u cive for hernia rep air scar form ation, treating
type IIIC. Type IV inguinal hernias are recurrent. the abd om inal w all like an orthop ed ic stru ctu re. A 3-d ay
Prosp ective nonrand om ized d ata and many large su p ervised convalescence is follow ed by a retu rn to nor-
review s suggest that recurrence rates should be low er for m al activity as com fort p erm its. The m axim u m convales-
type I and type II inguinal hernia repairs. These includ e cence p eriod is 4 w eeks for p atients involved in strenuous
simple and complex internal ring plasties follow ing high activity (Table 39.3).
ligation of an ind irect hernia sac. Su rgical experience su p-
ports the concept that the most d ifficu lt inguinal hernias to
repair are types III and IV. These includ e ind irect and d irect Table 3 9 .3 Sh ou ld ice clin ic p r in cip les of
hernias w ith significant posterior inguinal canal w all d eteri- in gu in a l h er n ior r h a p hy
oration, femoral hernias, and recurrent inguinal hernias.
Weight reduction
Open technique with complete anatomic dissection
■ Autologous tissue repairs Use of local anesthetics
Shouldice Repair Autologous tissue repairs
The p rincip les of the Shou ld ice rep air are a p arad igm for Early return to usual activity
the u se of au tologou s tissu es d u ring ingu inal hernia
Local anesthetic infiltration is used in association w ith w all blad d er com p onents. Finally, the inferior prep eri-
consciou s sed ation (d iazepam and m eperid ine). Aw ake toneal space is explored beneath the inferolateral transver-
proced u res u sing local anesthesia m ay red u ce card iac and salis flap to again rule out a femoral hernia com ponent.
pu lm onary com plications, especially in eld erly p atient The Shou ld ice rep air incorp orates an ind irect and d irect
popu lations. The incid ence of d eep venous throm bosis, reconstru ction in all instances, overlap p ing ingu inal floor
pu lm onary em bolism , and pu lm onary atelectasis is w ell m u scle and fascia in w hat is d escribed as their natu ral
below 1%. The Shou ld ice series m ortality is rep orted as sequ ence. Continu ou s m onofilam ent p erm anent su tures
0.01%. are u sed on the p osterior w all. A continu ou s sutu ring tech-
A com p lete d issection of all groin anatom y, norm al and niqu e is ad vocated to evenly d istribu te tension and to leave
abnorm al, is p erform ed . Prior to opening the external no gap s. The Shou ld ice Clinic p reference has been 34- or
obliqu e fascia, the inferior ed ge of the inguinal ligam ent is 32-gau ge stainless steel w ire becau se it is inert in tissu es
exam ined in the thigh to ru le ou t a fem oral hernia com po- and p rovid es m axim u m breaking strength for its caliber
nent. The external oblique aponeu rosis is incised and (tensile strength) and w ell-p laced knots m aintain integrity.
op ened from the external ring to 3 cm lateral to the internal Tw o d isad vantages of steel w ire inclu d e a tend ency to kink
ring. The lateral d issection ru les ou t an u nsu sp ected and break if m ishand led and the risk of laceration to su r-
Spigelian or interstitial hernia. The ilioinguinal and iliohy- geons and assistants. One continu ou s su tu re w ith tw o
pogastric nerves are id entified , isolated , and p reserved op p osing lines of rep air is then u sed to rep air the ingu inal
w ithou t inju ry if possible. The crem asteric m u scle fibers floor. The first layers ap p roxim ate transversalis fascia and
are then incised longitud inally, and the sperm atic cord p eritoneu m ru nning from m ed ially to laterally, and the sec-
w ith any associated ind irect hernia is freed from its sheath. ond layer ap p roxim ates m u scle and ap oneu rotic fibers
Uniqu e to the Shou ld ice techniqu e, crem asteric fibers are from the internal obliqu e and transversalis m u scles d ow n
then excised to facilitate accu rate transversalis fascia to fas- to the ingu inal ligam ent. Relaxing incisions on the ipsilat-
cia rep air. Part of the p roxim al stu m p of the crem asteric eral rectu s sheath are seld om requ ired , bu t are recom -
fibers is u sed d uring reconstru ction of the internal ring. m end ed if necessary p rior to the initiation of the first half of
The inferom ed ial stum p of the excised crem asteric fiber is the su tu re line. Tw o m ore lines of ru nning su tu re are then
inclu d ed in the rep air of the ingu inal floor in ord er to su s- p laced to reinforce the rep air. This tim e, starting ju st m ed ial
pend the testicle. Concern has been raised abou t testicu lar to the internal ring, the external obliqu e ap oneurosis is pli-
d ep end ency or even ischem ia follow ing the extensive cre- cated tow ard the p u bic crest and then reversed back to the
m asteric d issection and excision. internal ring. The external obliqu e ap oneu rosis is then
The internal ring is thorou ghly d issected . The p eri- closed in a continu ou s m anner, recreating the external ring.
toneu m is id entified and com pletely d issected back along Fem oral hernias m ay be a cau se of recu rrence follow ing
the sp erm atic cord . Most m ales have protru sion of p rep eri- hernia rep air, w hich is the reason for ad vocating that the
toneal fat at the su perolateral quad rant of the internal ring, fem oral sheath be rou tinely exam ined and even exp lored
w hich is u su ally not the sou rce of hernia sym p tom s u nless d u ring su p raingu inal herniorrhap hy. In the Shou ld ice
it extend s significantly (2 cm ) d ow n the sperm atic cord . series, 1 in 400 ingu inal hernia rep airs recu rred as a fem oral
The incid ence of slid ing hernias in the Shou ld ice series is hernia. Most op erative m od ifications ap p lied to red uce the
1%. Great care should be u sed to recognize a slid ing vis- incid ence of recu rrent fem oral hernias involve op ening of
cous com p onent at the internal ring, to w ork d istally to the posterior w all of the ingu inal canal (transversalis fas-
proxim ally to separate it from the spermatic cord and to cia) and closing the sp ace m ed ial to the femoral ou tlet (the
protect the slid ing organ’s blood sup ply. If the ind irect her- fem oral ring) u sing Coop er ligam ent. Conversely, w hen
nia sac is transected at the internal ring, som e au thors rec- only a fem oral hernia w as su sp ected on clinical ground s,
om mend leaving the d istal end of the sac in situ to avoid sim ultaneous significant su praingu inal p athology w as
sp erm atic cord injury and to red uce the risk of an ischem ic d etected at op eration in 87% of m ales and 63% of fem ales in
testicle or testicu lar atrop hy. Others ad vocate d issection of the Shou ld ice series (31). This observation reinforces the
the rem nant sac from the sperm atic cord to eliminate the need for carefu l and com p lete su p raingu inal and infrain-
possibility of hyd rocele. Most series report an incid ence of gu inal examination d uring all inguinal hernia repairs in
testicu lar atrop hy of 0.1%. The Should ice experience also ord er to m inim ize recurrence rates.
su ggests that ligation of ind irect hernia sacs is not m and a- The incid ence of recu rrent hernia increases w ith each
tory. In their view, com plete red uction of the hernia sac su bsequ ent rep air, m ost likely d u e to tissu e loss and scar-
w ith m eticu lou s reconstru ction of the internal ring m ini- ring (32,33). H ighest recu rrence rates (12%) are reported
m izes recu rrence rates. follow ing rep airs of m u ltip ly recu rrent ingu inal hernias.
The Shou ld ice techniqu e requ ires incision and op ening Becau se recu rrent w ou nd failu re ap p ears to select abnor-
of the p osterior w all of the ingu inal canal (the ingu inal m al scar and fascia exp ressing a tissu e rep air d efect, the
floor), w hich is com posed m ainly of transversalis fascia. im p lantation of p rosthetic m aterial has been ad vocated .
Any d irect hernias thus encountered are carefully red u ced . The interval betw een the first and second op erations
If opening of a d irect hernia sac is required , it is perform ed shou ld be at least 6 m onths to allow op tim u m recovery of
from the lateral ed ge to avoid inju ry to p otential m ed ial the tissu e to be u sed again for rep air. When the inguinal
ligam ent w as intact, an au tologous tissue repair w as p ossi- Synthetic Tissue Implants (Mesh)
ble in 91% of the cases of recurrent hernia repair in the Billroth w rote in 1878, “If w e cou ld artificially prod uce tis-
Shou ld ice exp erience. For the rem aining 9% of patients, the sues of the d ensity and toughness of fascia and tend on, the
groin d efect w as d escribed as too extensive or the groin tis- secret of the rad ical cure of hernia w ould be d iscovered ”
su e as too friable and inelastic to allow au tologou s tissu e (34). In ad d ition to replacing d efective soft tissu e, synthetic
repair. In these cases, an allop lastic prosthetic im plant in mesh implants are believed to red uce the chance for
the prep eritoneal sp ace w as u sed . When the bow el w as “missed ” hernia. Recu rrent hernias often result from simul-
covered w ith p eritoneu m , p olypropylene m esh w as u sed . taneou s ingu inal d efects that w ere m issed at the tim e of the
When the bow el w as exposed , a m icroporou s PTFE p atch initial herniorrhap hy. Covering the entire m yop ectineal
w as u sed . With a m inim u m follow -up of 18 m onths, the orifice w ith a p rosth esis shou ld red u ce th e incid en ce of
reported recu rrence rate w as 2.2% (31). missed simultaneou s hernia. Finally, replacing or augment-
Cooper Ligament Repair ing abnormal inguinal soft tissue may prevent the d evelop-
ment of future hernias.
The first reported use of the Cooper ligament (the superior Tod ay, variou s p rosthetic m eshes are available for her-
pubic ligament) in hernia rep air w as to treat femoral hernias nia rep air. Knitted p olyp rop ylene m esh is u sed m ost com -
by su turing the ingu inal ligament d ow n to it, obliterating m only. This material ind uces a rapid and reliable fibroblastic
the femoral sheath space (30). Later, McVay popularized the response and is efficiently incorporated into the abdominal
technique by recommend ing a rectus sheath-relaxing inci- w all. Synthetic meshes, how ever, tend to stiffen and shrink
sion and transfer of the transversalis abd ominus aponeu ro- over time, inducing d isorganized scar tissue. Polyethylene
sis and muscle and transversalis fascia d ow n to the Cooper meshes are hyd rophilic and more pliable than most heavy-
ligam ent in ord er to repair the ingu inal canal’s posterior w eight or small-pore polypropylene meshes. PTFE meshes
w all. This maneuver requires opening the floor of the are extruded with a microporous surface to allow abdominal
ingu inal canal and exploring the p reperitoneal space. This w all fibroblast and macrophage ingrowth for abdominal wall
ad d ed d issection is also believed to red uce the incid ence of incorporation and immune surveillance, while at the same
missed hernias, especially femoral hernias. time minimizing ad herence to the bowel and other intraab-
In m ost d escrip tions, the ilioingu inal nerve is p re- d ominal viscera.
served . If the nerve is trau m atized d u ring groin d issection, The term “tension-free” hernioplasty was first published
many experts recomm end ligation and d ivision of the by Lichtenstein et al. in 1986 (35,36). That report d escribed an
nerve to red u ce the incid ence of postoperative chronic pain onlay technique using sutured polypropylene mesh. What
synd rom es. The sp erm atic cord is fu lly m obilized in the w as most significant about this approach w as that the mesh
inguinal canal. N o d issection is perform ed m ed ial to the w as not used as reinforcement to an antecedent autologous
pubic tu bercle in ord er to avoid inju ry to the external tissue reconstruction, but defined the repair itself. N o
pud end al blood su p p ly and to preserve collateral circu la- attempt is mad e to use abnormal autologous groin tissues in
tion to the testicles. Starting laterally, the anterior su rfaces the reconstruction. The initial report from this noncontrolled
of the fem oral artery and vein are cleared and the anterior or randomized, single experience cited 1,000 consecutive
fem oral fascia is id entified . Working m ed ial to the fem oral repairs w ith no recurrences over 5 years.
vein, fat and lym p hatics are d issected free from the fem oral
canal and any fem oral sac is red uced . The tend inou s p or-
tion of the transversu s abd om inis ap oneu rotic arch is then Mesh Plugs
id entified , and a relaxing incision is placed at the p oint of Another su rgical concep t d evelop ed to rep lace or au gm ent
fu sion of the external obliqu e mu scles and the rectu s biologically d efective groin tissu e and achieve tension-
sheath. This starts at the pu bic tu bercle and then extend s ap p rop riate rep airs w as m esh-p lu gging herniorrhaphy
sup eriorly by 6 to 8 cm . The rem aind er of the repair can be (Fig. 39.4). This w as first d escribed by Lichtenstein and
perform ed w ith the patient in the Trend elenbu rg p osition Shore in 1974 for the treatm ent of recu rrent or fem oral her-
to m inim ize intestinal injuries. In ind epend ent, noncon- nias (37). In this op eration, the hernia sac is d issected and
trolled , or rand om ized series, recurrence rates of 2% have red u ced to the level of the m yofascial hernia ring. The sac
been rep orted by high-volu m e su rgeons w ho lim it their neck is then d issected from the hernia ring, and the hernia
practice to herniorrhap hy (30). is invaginated w ithou t ligation or excision. A sheet of syn-
The d isad vantages of the Cop p er ligam ent (McVay) thetic mesh (u su ally knitted p olyp rop ylene) of d im ensions
rep air inclu d e the m ore extensive d issection and rep orted of ap p roxim ately 2 cm 20 cm is rolled into a cylind rical
prolonged recovery p eriod . Som e authors have argu ed that shap e that best fits the d efect. The p lu g is inserted into the
the tension p laced on the p osterior w all rep air is su bop ti- p reperitoneal space until the outer ed ge is flu sh w ith the
mal as w ell and that vascu lar injuries are m ore com m on hernia d efect m argin and secu red into p lace w ith circu m -
w ith the McVay rep air. Proponents of this proced u re rec- ferential interru p ted su tu res. Single institu tion series w ith
om m end relaxing incisions and carefu l d issections arou nd m inim u m follow -u p of 1 year rep orts recu rrence rates of
the fem oral vessels to achieve a reliable p roced u re w ith low 5%. Prop onents of the techniqu e argu e that it is sim ple to
recu rrence rates and m inim al m orbid ity. learn and safe. The minim u m d issection requ ired low ers
FIGURE 39.4. Mesh-plug inguinal

herniorrhaphy starts with a careful
dissection of the limits of the hernia
sac (A), reduction of the hernia sac to
HRFischer '04 the preperitoneal space and the siz-
ing of a cone-shaped mesh plug (B),
and anchoring of the seated mesh
plug to the surrounding transversalis
fascia or mature hernia ring with sev-
eral interrupted sutures. (continued)
Direct hernia sac
HRF '04
Hernia defect
Mesh plug
the incid ence of ingu inal nerve and ad jacent organ inju ry. ad jacent organ inju ry, w ith equ al m ed iu m -term resu lts.
In ad d ition, the absence of extensive groin d issection and The m esh p lu g and m esh p lu g com bined w ith a m esh sheet
op ening of the ingu inal floor p revents iatrogenic inju ry to onlay ap p ear m ost am enable to N yhu s typ es I and II (ind i-
the stru ctu res of the inguinal canal. A com m on m od ifica- rect) ingu inal hernia rep airs and to easily d efinable recu r-
tion of the m esh-p lu g techniqu e inclu d es the ad d ition of a rent ingu inal hernias.
sheet m esh onlay onto the floor of the ingu inal canal fol-
low ing im p lantation of the m esh plu g. Proponents of this Preperitoneal Inguinal Hernia Repair
techniqu e believe this rep air can be d one w ithou t su tu re The p osterior ap p roach to the ingu inal canal and iliop u bic
anchors, again low ering the risk of inguinal nerve and tract rep air u sing a p rosthetic bu ttress has rep orted su ccess
FIGURE 39.4. (Continued) Some

surgeons advocate the addition of a
mesh onlay, often without sutures or
tacks, to reinforce the plug and to
protect against herniation through HRF '04
adjacent tissue within the floor of
the inguinal canal (Cand D).
Mesh fixation
HRFischer '04
Mesh onlay
in both com plicated p rim ary and recu rrent ingu inal her- incision p laced 4 cm su p erior to the p u bic sym p hysis.
nias (N yhu s typ es III and IV) (38,39). Proced ures to rep air The incision is slightly higher than that u sed for anterior
the iliop u bic tract u sing a p osterior ap p roach have several ingu inal herniorrhap hies. The external ring is id entified so
im m ed iate ad vantages. Prim ary among these is operation that an estim ation of the location of the internal ring m ay
for recu rrent hernia, w here d issection can be carried ou t be m ad e. The p osterior ap p roach to the floor of the
throu gh u nscarred and u nd istorted p rep eritoneal tissu e ingu inal canal requ ires that the abd om inal w all incision be
planes. All d efects w ithin the m yopectineal orifice can be fashioned above the internal ring. The transversalis fascia
red uced and rep aired via the sam e incision. These p rinci- is incised transversely, and the p rep eritoneal sp ace is care-
ples have now been ad ap ted to m inim ally invasive tech- fu lly d evelop ed w ith blu nt d issection. It is u su ally u nnec-
nologies. The p rep eritoneal space can be entered and essary to ligate and d ivid e the d eep inferior ep igastric
d evelop ed u sing tw o or three 5- or 10-m m incisions and an vessels in ord er to achieve ad equ ate exp osu re. The inferior
id entical repair com p leted laparoscopically. ep igastric vessels can be inad vertently inju red at the lat-
An op en ap p roach to the p rep eritoneal sp ace is typ i- eral m argin of this incision. Care m u st be u sed to avoid
cally com p leted u sing a transverse low er abd om inal w all u nintend ed op ening of the p eritoneu m and entry into the
p eritoneal cavity. Exam ination of the p osterior w all of the location makes the incidence of significant postoperative
ingu inal canal allow s for d iagnosis and red u ction of her- bleeding very low following the preperitoneal approach.
nia d efects. Most d irect hernia sacs are easily red u ced and Investigators have reported a low er incid ence of testicular
inverted . A large d irect hernia sac m ay be invaginated atrophy and chronic neuropathic pain follow ing the poste-
u sing a p u rse-string su tu re carefu lly p laced in the trans- rior preperitoneal approach to inguinal hernias (39), believed
versalis fascia or ap oneu rosis. Inju ry to the ad jacent blad - to be the result of sparing injury to the inguinal nerve supply
d er shou ld be avoid ed , esp ecially if a d ecision is m ad e to that courses lateral and anterior to this operative field.
excise a d irect hernia sac. In p erform ing an au tologou s tis- Reported hernia recurrence rates average 3% to 6%.
su e rep air, the su p erior transversalis fascia and ap oneu ro- The p rep eritoneal p osterior rep air of recu rrent ingu inal
sis of the transversalis arch are typ ically sew n to the hernias is u su ally “bu ttressed ” w ith an ap p roxim ately
iliop u bic tract to close the d irect d efect. Med ially, the 5 cm 12 cm p olyp rop ylene m esh that is anchored to the
su tu re m ay also be p assed throu gh both the Coop er liga- Cooper ligam ent and the transversalis fascia sup erior to
m ent and the m ed ial iliop u bic tract for reinforcem ent. the p reviou s rep air. The p rep eritoneal p osition of the m esh
If there is an ind irect hernia, the sac is red u ced w ith im plant im p arts a m echanical ad vantage to the rad ial load
carefu l traction and a high ligation is perform ed . If d issec- forces of the abd om inal w all.
tion of a large ind irect hernia sac is d ifficu lt, abd om inal
organs are red u ced and the sac m ay be transected at its Laparoscopic Inguinal Herniorrhaphy
neck and closed w ith a pu rse-string su ture. The d istal sac is Various lap aroscopic techniques for repairing inguinal her-
left open to m inim ize the incid ence of postoperative hyd ro- nia are the new est d evelopm ents in the long history of her-
cele. An internal ring plasty is then perform ed . nia su rgery. Prop onents of lap aroscop ic ap proaches to
Fem oral hernias may also be gently red uced via the inguinal herniorrhaphy argue that they are the m ost
preperitoneal app roach. If there is an incarcerated femoral anatom ically ap p rop riate. The ad vantages are a clear, u p-
hernia, it m ight be released by incising the insertion of the close vid eoscopic exam ination of the posterior ingu inal
iliop ubic tract to the Cooper ligam ent at the m ed ial bord er floor and m yop ectineal orifice, sim u ltaneou s exam ination
of the femoral ring. Once red uced , the femoral sheath d efect of the three major sites of ingu inal herniation (internal ring,
is obliterated using su tures betw een the iliop ubic tract and H esselbach triangle, and fem oral triangle), and the m ost
the Cooper ligament. On rare occasion, a counter incision in mechanically ad vantageou s rep air. Follow ing red uction of
the upper thigh over an incarcerated femoral hernia may be hernia contents, reinforcem ent of all m yop ectineal d efects
necessary to affect a safe release from restricting fascia. This is com p leted in the p rep eritoneal p osition. Placem ent of a
should , how ever, be an uncommon maneuver. mesh prosthesis posterior to the inguinal floor is su ch that
Hemostasis is especially important during the preperi- d istractive forces originating in the p eritoneu m tend to
toneal approach. A relatively larger potential space exists for secu re the p rosthesis in p lace.
hematoma accumulation follow ing the preperitoneal dissec- The m ost com m only rep orted techniqu e for lap aro-
tion. However, the tamponading effect of the peritoneal sac scop ic ingu inal hernia rep air tod ay is the totally extrap eri-
and preperitoneum once it is returned to its normal anatomic toneal p rep eritoneal ap p roach (TEPPA) (Fig. 39.5). Like
FIGURE 39.5. The TEPPA during

laparoscopic inguinal hernia repair
requires the development of the
preperitoneal space of the lower
abdominal wall. This allows a poste-
Rectus Psoas muscle rior approach to the potential and
real defects of the inguinal canal.
abdominis
Important nearby structures are
muscle
Gonadal vessel illustrated, including the vas defer-
ens, iliac vessels, inferior epigastric
vessels, rectus muscle, and inguinal
Inferior ligament. Mesh delivered into this
epigastric preperitoneal space may be secured
vessels in place by the radial pressure of the
peritoneal sac following desuffla-
tion. This finding has led to the
Vas deferens successful development of TEPPA
Inguinal ligament inguinal hernia repairs without the
need for suture or tack fixation. It is
believed that this modification low-
ers the incidence of chronic pain
syndromes due to nerve injuries.
most lap aroscop y, TEPPA herniorrhap hy requ ires a general cou rse of the ilioingu inal, iliofem oral, and hypogastric
anesthetic. The op eration begins w ith d issection and d evel- nerves (40).
opm ent of a p rep eritoneal space. This d issection is typ i- The transabd om inal p rep eritoneal (TAPP) ap p roach for
cally achieved through an infrau mbilical incision w ith laparoscopic ingu inal hernia repair w as d escribed before
su bsequ ent incision of the anterior rectu s sheath and lateral the TEPPA techniqu e w as d evelop ed . The TAPP ap proach
retraction of the rectu s m uscle. A balloon d issector m ay be is intraabd om inal and has a higher risk of abd om inal organ
d irected tow ard the pu bic sym physis and inflated slow ly inju ry. The hernia d issection is som ew hat easier becau se
to create this op erating space. Som e su rgeons om it u sing a the sp ace is greater. The p rep eritoneal sp ace is u ltim ately
balloon d issector and create the p reperitoneal space u sing exp osed w ith this ap p roach as w ell. It is im p ortant to incise
finger or hem ostat d issection. com p letely throu gh the p eritoneu m and p rep eritoneu m
Great care m u st be exercised to avoid inad vertent entry p osterior to the ingu inal floor u ntil the areolar space of
into the p eritoneal sp ace, w hich obviates the ad vantages of Bogros is entered betw een the transversalis fascia and the
the TEPPA ap p roach. The m ost obvious ad vantage of the p eritoneu m . If not, d issection in the am orp hou s prep eri-
TEPPA ap p roach is the ability to stay ou t of the p eritoneal toneal fat and fascia m ay lead to bleed ing and confu sion
cavity and red u ce the chance of inju ry to abd om inal abou t ingu inal anatom y.
organs. The p rep eritoneal space is fairly avascu lar, w ith Com p lications u niqu e to the lap aroscop ic ap p roach to
occasional sm all vessels traversing betw een the transver- ingu inal herniorrhaphy includ e trocar inju ries and prob-
salis fascia and the reflected peritoneum . If a balloon d is- lem s w ith insu fflation. The op erating sp ace for the TEPPA
sector is u sed , it m ay rem ain inflated for several minu tes to p roced u re is a m u ch sm aller volu m e than for intraperi-
tam ponad e these crossing vessels. Significant hem atom as toneal lap aroscop ic op erations. Op erating p orts should
can form in the p reperitoneal space, especially in old er alw ays be p laced u nd er d irect vision so that inju ry to ad ja-
patients w ith m ore areolar tissu e planes. cent stru ctu res and organs m ay be avoid ed . Inju ry to the
An ad equ ate d issection shou ld extend ju st beyond the inferior epigastric vessels can cau se significant bleed ing.
mid line, below the Cooper ligam ent (6 to 8 cm below the Blu nt, rad ially d ilating p orts have low er incid ences of ad ja-
inguinal ligam ent), w ell above the transversus abd om inis cent organ inju ry and low er abd om inal w all com plications
aponeu rotic arch, and w id ely beyond the internal ring. than blad ed lap aroscop ic p orts. Occasionally, insufflation
Exp erts report that an inad equate d issection of the peri- of the p rep eritoneal sp ace w ill resu lt in u nexp ected p neu -
toneu m aw ay from the p osterior ingu inal w all is the m ost m op eritoneu m . This occu rrence su ggests the p resence of a
com m on reason for recu rrent hernias follow ing TEPPA d efect in the p eritoneu m. If a d efect in the p eritoneum is
rep airs. id entified , the hole shou ld be closed w ith su tu res or clips,
An ap p rop riately sized p iece of syn th etic m esh taking care to p rotect against inju ry to intraabd om inal
( 12 cm 6 cm ) is d elivered via the end oscopic p ort site organs. Prep eritoneal insu fflation m ay ind u ce the sam e
into the p reperitoneal space to reinforce the posterior w all hem od ynam ic changes observed d u ring intraabd om inal
of the ingu inal canal. Debate exists on w hether it is neces- lap aroscop ic p roced u res, u su ally the resu lt of red uced
sary to secu re this m esh in p lace w ith either su tu res or venou s retu rn. One d istressing effect of p rep eritoneal
tacks. It is also u nclear w hether it is necessary to split the insu fflation is the appearance of scrotal d issection and
m esh and encircle the sperm atic cord through a “keyhole.” p neu m oscrotu m . This d evelop m ent is alm ost u niform ly
Proponents argu e that a m inim u m of m esh anchors p laced self-lim iting, and p atients shou ld be reassu red . With expe-
into the transversalis fascia and encircling of the spermatic rience, TEPPA rep airs m ay be p erform ed at low er insuffla-
cord through a slit mesh results in low er hernia recurrence tion p ressu res to m inim ize su bcu taneou s em p hysem a.
rates. Opponents suggest that anchoring the mesh and the
additional dissection of the spermatic cord increases the inci- Autologous Tissue Transfers
dence of postoperative chronic pain. N o definitive rep orts Recu rrent hernias often occu r becau se of local tissu e loss
have resolved these technical issu es. and or the failu re of collagenou s tissu es to obliterate the
The TEPPA rep air can resu lt in recu rrence rates equ iva- cou rse of a hernia or becau se of infection and contraind ica-
lent to op en herniorrhaphy, w ithout significant w ou nd ing tion to synthetic m esh p lacement. When su fficient collage-
of the anterior abd om inal w all and , therefore, w ith a low er nou s m aterial is not p resent, it may be necessary to transfer
w ou nd com p lication rate. Recu rrences tend to occur m ed i- su ch tissu e into the op erative field . Frequ ently u sed tech-
ally w here the iliac vessels p ass beneath the m esh or later- niqu es inclu d e harvest and im p lantation of free tensor fas-
ally, esp ecially w hen there is d ilated internal ring. For these cia lata and the tensor fascia lata myocu taneou s flap .
reasons, the m ed ial and lateral m esh ed ges are often held in Tensor fascia lata free grafts are id eal for sm all area d efects
place d u ring d esu fflation after unilateral TEPPA rep airs. u nd er m ed iu m to low abd om inal w all load s. The risk of
There is a slightly earlier retu rn to u su al activities follow - u sing tensor fascia lata is m echanical failu re parallel to the
ing TEPPA ingu inal herniorrhaphy. The incid ence of neu roline of collagen bu nd les and the requ irem ent for lateral
pathic p ain follow ing laparoscopic ingu inal hernia rep airs thigh w ou nd s to harvest the grafts. Allop lastic im plants
is m inim ized if anchoring tacks or su tures, or both, are like p olyp rop ylene or p olyethylene have higher tensile
p laced above the ingu inal ligam ent and aw ay from the strengths, bu t have a higher incid ence of bow el fistulization
and foreign bod y infections. Collagen-based biological Table 3 9 .4 Risk fa ct or s for wou n d in fect ion
mesh im plants offer a potential alternative w ithou t the follow in g in cision a l h er n ia r ep a ir
need for the w ou nd ing of au tologous d onor sites.
Operative time
Strangulated Hernias
Devascularized tissue
If the preoperative evaluation raises any concern for a stran-
Obesity
gulated viscu s, a transperitoneal approach to the involved
bow el shou ld be strongly consid ered . Transperitoneal exp o- Hematoma formation
sure of the unaffected intestine at the hernia ring improves Foreign material (mesh)
the control of the gangrenous bow el segment. The posterior Bowel or bladder injury
iliop ubic tract repair m ay follow intestinal resection and
Malnutrition
anastomosis. In the obese p atient, it may be d ifficult to d iag-
nose im pend ing strangulation d u e to hernia incarceration. Advanced age
A high ind ex of su sp icion m u st be m aintained . Im aging Chronic disease
stud ies may show soft-tissue gas, bow el w all thickening, or Polypharmacy
free air. The skin overlying the strangulation may be firm,
erythem atou s, and tend er.
increases the risk of unplanned visceral inju ries d u e to the

■ Incisional hernias requ irem ent for ad hesiolysis and enterolysis. Blood loss
Incisional hernia is the m ost com m on ind ication for reop er- m ay also be increased , d ep end ing on the extent of the
ation in abd om inal su rgery p atients (3). Many recu rrent ad hesiolysis. Many p rosp ective series have d ocum ented
ingu inal hernias are also incisional hernias. Incisional her- the extrem ely high incisional hernia recu rrence rate follow -
nias are uniqu e becau se they are the only abd om inal w all ing rep air w ith local, au tologou s tissu e (24% to 54%) (3–5).
hernias consid ered iatrogenic. Because the reported inci- Recent large review s have also found an increased risk
d ence of acu te fascial d ehiscence is 0.5% and the incid ence of w ou nd infection follow ing incisional hernia rep air
of p rim ary incisional hernia form ation is 11%, it is clear that (25,26). The risk factors for incisional hernia form ation and
many incisional hernias go unrecognized in the early p ost- the risk factors for w ou nd infections are often the sam e.
operative p eriod (16,18). It ap pears that the incid ence of These risks inclu d e obesity, m alnu trition, ad vanced age,
incisional hernia approached one in three in patients w ith a chronic p u lm onary d isease, and p olyp harm acy. Wou nd s
BMI 35 (obese). follow ing incisional hernia rep air are at increased risk for
Fascial w ound healing achieves only 60% to 80% of infection d u e to technical factors like prolonged operations,
unw ounded fascial strength after 6 weeks (29). Collagen hematom a form ation, d evascu larized or ischem ic tissue,
deposition and fiber orientation along lines of stress occur bow el inju ry, and the p resence of foreign m aterial su ch as
during this interval. Nine to 12 months pass before fascial p reviou sly p laced mesh (Table 39.4).
scar approaches uninjured breaking strength. For this rea- A p rosp ective, rand omized , and controlled stud y of
son, m ost p atients shou ld be cau tioned to avoid overload - incisional hernia repair conclud ed that m esh im plantation
ing their abd om inal w all for at least 6 w eeks follow ing is requ ired to achieve the low est recu rrent hernia rate (4,5).
celiotom y. A com m on practice is to resum e near-norm al In p ractice, synthetic m esh im p lantation is not alw ays a
activity and abd om inal w all load s 2 w eeks follow ing fas- clinical op tion or the p atient’s p reference, and even w ith
cial closu re, w ith great care to load the abd ominal w ound m esh im p lantation, the recu rrent incisional hernia rate w as
only as comfort permits. Patients should be ed ucated about still 24%. For all these reasons, au tologou s tissue closu res
the biology of w ound repair and the need to restrict sud d en are still occasionally recom m end ed and u nd ertaken.
loads of their ventral wounds, as w ith coughing or sneezing. The size of the fascial d efect and the quality of the fascia
Su ccess of incisional hernia rep air d ep end s on basic su r- should guid e the selection of the hernia repair. The skin and
gical p rincip les. These precepts includ e the incorp oration subcutaneous tissue are d issected aw ay from the hernia sac,
of norm al fascial tissu e brou ght together u nd er a p hysio- bu t great care shou ld be u sed to preserve the blood su pply
logic abd ominal w all load and the avoid ance of the risk fac- to the overlying skin. Viable skin provid es the most impor-
tors for recu rrent herniation. tant coverage for the und erlying hernia repair, by w hatever
method . N ormal-appearing fascia should be id entified back
from the fascial hernia ring on both ventral and peritoneal
■ Autologous tissue repairs surfaces. A minimum of 3 cm of fascial exposure for suture
At first, incisional hernia repairs m ad e u se of local, au tolo- placement is the pu blished expert consensus (41).
gous abd om inal w all tissue to correct abd om inal w all If a fascial d efect is so large as to preclu d e incisional her-
d efects. Most often, this am ou nted to no more than reclo- nia rep air by sim p le reclosu re, a nu m ber of other repairs
su re of a lap arotom y incision or m atu re incisional hernia u sing au tologou s tissu e have been d escribed . Sim plest
ring. The reop erative nature of incisional herniorrhap hy am ong these is the u se of internal retention su tures. Other
variations of local m yofascial relaxing incisions are u sed . compromise the integrity of the rectus sheath. All variations
During the Keel p roced ure, vertical relaxing incisions are of abd ominal w all component separations increase the risk
placed along the lateral ed ge of the anterior rectu s sheath, for bleed ing and hematoma/ seroma form ation. Prolonged
allow ing m ed ial ad vancem ent of the m ed ial ed ge of the subcutaneous d rainage is frequently ind icated and recom-
anterior rectu s sheath. This app roach is especially u sefu l in mend ed . The risk for overlying skin necrosis is increased
upper m id line abd om inal w all hernias, w here a stout p os- because of the necessity for wid e skin flaps. Wound ischemia
terior rectu s sheath p rotects against fu rther iatrogenic is minimized by the preservation of periumbilical vascular
injury (42). For m id line d efects in the low er abd om en, stalks traveling from the myofascial of the rectus component
mobilization of the low er section of rectu s m u scle and to the ventral skin.
envelop ing fascia and reap proxim ation to the contralateral
sid e has been d escribed . Synthetic Abdominal Wall Meshes
Abdominal w all component separation techniques have The im plantation of synthetic tissu e prostheses w as intro-
gained in popularity in an effort to reconstruct large abd om- d u ced to incisional herniorrhap hy in an attem p t to red u ce
inal wall defects, restore abdominal wall function, and mini- the u nacceptably high incisional hernia recurrence rates
mize the use of synthetic mesh implants in contaminated or w hen u sing only local, au tologou s tissu e for reclosure (Fig.
infected operative fields (43). Fund amentally, these opera- 39.6) (44). Prosp ective, rand omized stu d ies fou nd that an
tions includ e the elevation of w id e, lateral skin flaps to id en- ind ep end ent risk factor for recu rrent incisional hernia is
tify the und erlying m yofascial anatomy and to release the the techn iqu e of p rim ary tissu e rep air w ith ou t th e u se of
fascia from its d ermal attachments. Next, the full length of a m esh im p lant (4,5). Synthetic im p lants are, how ever,
the external oblique muscle is incised , usually from the associated w ith a characteristic set of com p lications. First
costal margin to the pubis. Great care is used to preserve the am ong these com p lications is m esh-associated infection
integrity of the underlying internal oblique and transversalis and foreign bod y inflam m atory reaction. The risk of m esh
muscles. The subcostal and lateral segmental nerve supply infection and p rolonged inflam m ation is greatest follow ing
to the anterior abd ominal w all run in the plane betw een the incisional ventral hernia rep air (26). Other series report a
internal oblique and transversalis muscles. Inad vertent significant incid ence of chronic pain follow ing m esh
entry into this plane and nerve injury may cause anterior im p lantation (45–47).
eventration d ue to d enervation. The external oblique inci- The m ost com m only u sed m esh m aterials are knitted
sion is typically placed 1 cm lateral to the lateral ed ge of m onofilam ent p olyp rop ylene (Marlex), w oven p olyp rop y-
the rectus sheath (linea semilunaris). This maneuver pro- len e (Prolene), w oven p olyester (Mersilen e, Parietex),
vid es on average 4 to 6 cm of med ial ad vancement of the exp and ed or extru d ed p olytetraflu oroethylene (ePTFE,
rectus sheath. Anterior rectus sheath or posterior rectus Gore-Tex), knitted p olyglycolic acid (Vicryl), and knitted
sheath relaxing incisions may be ad d ed to increase the p olygalactic acid (Dexon) (48–50). N ew er fabric d esigns for
ad vancement d istance of the mid line, althou gh this may the w oven m eshes suggest that lighter polym er w eights
FIGURE 39.6. The best available evi-

dence suggests that a mesh “under-
lay” technique results in the lowest
recurrence rates following incisional
hernia repairs. Anatomically, retro-
fascial/retromuscular, preperitoneal,
and intraperitoneal mesh fixation is
described. Circumferential, transfas-
cial, or transabdominal fixation sutures
are frequently used following the
repair of large incisional hernias or
when using the laparoscopic technique.
and large w eave pore size low ers the foreign bod y inflam - p rim ary reclosu re w ithou t the u se of m esh, p ostoperative
matory resp onse and im proves incorporation. PTFE gained p rostatism , and a history of abd om inal aortic aneu rysm (4).
pop u larity becau se of its reported red u ced tissue reactivity These find ings p oint to p otential m echanism s for recu rrent
and ad hesion form ation, although concerns have been incisional herniation. The first tw o cond itions highlight the
raised abou t serom a form ation and m esh infection rates. im portance of increased m echanical load s on abd om inal
Most au thors conclu d e that absorbable m esh shou ld not be w all hernia recu rrence. The history of aortic aneurysm d is-
used for p erm anent abd om inal w all reconstru ction ease su ggests biological risk factors for hernia recurrence,
becau se of the u niversal d evelop m ent of recu rrent inci- su ch as the elevated exp ression of tissu e m etallop roteinase.
sional hernias and an increased risk for bow el fistu lization Typ ically, recu rrent incisional hernias are sm all in area or
(Fig. 39.6). volu m e as the resu lt of a limited d isru p tion, usu ally
Seriou s com p lications have been observed in p atients betw een the synthetic m esh and the fascia. Often, a sim ple
after incisional hernia rep airs w ith synthetic m esh im p lan- rep air can be u nd ertaken, d irected to the area of this d efect
tation. The m ost im portant seriou s p roblem s are m esh- (Fig. 39.7). When m esh failu re occu rs, it is alm ost alw ays at
associated infection, chronic skin sinu s tract form ation, the m esh:fascia interface rather than m esh m aterial central
erosion into ad jacent structures, inclu d ing bow el, and failu re.
chronically exp osed or extru d ed m esh (51,52). Mesh p lace- Infection increases the risk of hernia recu rrence. Deep
ment in the p resence of heavy contam ination w as rep orted w ou nd infections p rolong inflam m ation and imp ed e colla-
to be associated w ith a 50% acu te w ound failu re rate gen d ep osition. Elective rep air shou ld therefore not be
(d ehiscence) and 22% enteric fistulization rate. Ad m inistra- attem p ted if any signs of infection exist, su ch as a stitch
tive d atabases now rep ort that the p resence of a synthetic abscess or sinu s or overlying skin excoriation. Foreign
mesh in the intraperitoneal position increases the risk of an m aterials associated w ith infections shou ld be rem oved
unp lanned enterotom y or bow el resection from 3% to 23% and the overlying skin healed p rior to hernia repairs.
d u ring su bsequ ent abd om inal operations (8,9). The u se of au tologou s local tissu es is som etim es p re-
ferred d u ring ventral hernia rep air. A com mon situation
Recurrent Hernia occu rs w hen infected synthetic m esh is rem oved . The
A p rosp ective, rand om ized stud y of incisional hernia au tologou s tissu es m ay be m obilized u sing com ponent
rep air fou nd that risk factors for recu rrent hernias inclu d ed sep aration of the abd om inal w all. One or both sid es of the
FIGURE 39.7. When detected

HRFi early, recurrent incisional hernias
sc her '04 are usually of a small area or vol-
ume as a result of a limited disrup-
tion. The mechanism of recurrent
incisional hernia formation includes
a failure of tissue repair at the inter-
face between the mesh implant and
the native fascia. Often, a limited
salvage repair can be undertaken,
directed to the area of this defect.
Recurrent
inguinal hernia
abd om inal w all m ay not be am enable to com ponent sep a- controlled , 6 to 8 w eeks of bow el rest shou ld be allow ed to
ration becau se of p reviou s existing d efects su ch as stom a p ass to p erm it sp ontaneou s closu re. This is m ost likely in
sites. the setting of low or m ed iu m ou tp u t fistu lae. If closure
d oes not occu r, this p eriod of time w ill allow su rrou nd ing
Giant Ventral Hernias tissu e inflam m ation and infection to im p rove in anticip a-
Patients w ith m assive incisional hernias usu ally p resent tion of d efinitive rep air. When op erative closu re of an
w ith fu nctional loss of the abd om inal w all and su bstantial enteric fistula is planned in association w ith a recu rrent
protru sion of abd ominal viscera. Su ch hernias are fre- hernia rep air, p reop erative d iagnostic staging shou ld be
qu ently associated w ith chronic abd om inal pain, chronic d one to p recisely id entify the fistu la’s anatomy, and espe-
back p ain, and erosion of overlying skin. Severe skin lym - cially id entify and m anage d istal gastrointestinal strictures
phed em a m ay ensu e. Peritoneal volum e (abd om inal cau sing obstru ction. Every effort shou ld be m ad e to repair
d om ain) is grad ually lost as abd om inal viscera rem ain her- the abd om in al w all d efect w ith au tologou s tissu e, su ch as
niated . Massive ventral hernias w ith significant loss of a local ad vancem en t flap or free ten sor fascia lata. Com -
abd om inal d om ain also can cause d iaphragm atic d ysfu nc- m ercially available biological collagen p rostheses offer
tion and intestinal circu latory congestion (38). an alternative to the ad d ed w ou nd ing of au tologou s tissu e
The techniqu e of serial p reop erative therap eu tic p neu - harvesting and the u npred ictability of the m echanical
moperitoneum to reestablish abd om inal d om ain offers one integrity of tensor fascia lata, for examp le.
approach to the p roblem of peritoneal volum e loss (38).
This m ethod has lost p op u larity w ith the increased u se of Vascular Injuries
“tension-free” m esh-based repairs. Because the incid ence Inad vertent injury to an aberrant inferior ep igastric or
of p rim ary and recu rrent incisional hernias rem ains so high obtu rator artery m ay occu r d u ring low er abd om inal w all
and the com p lications associated w ith synthetic m esh hernia rep airs. Inferior ep igastric inju ries m ay result in sig-
im plantation have not been solved , there is renew ed inter- nificant hem orrhage. Another sou rce of inferior epigastric
est in tissu e expansion and other techniques for the d evel- artery inju ry is the placement of low er abd ominal w all ports
op m ent of au tologou s tissu e sou rces to rep air these for lap aroscop ic hernia op erations. Op en ingu inal floor
d ifficu lt w ou nd s (53,54). rep airs, su ch as the Coop er ligam ent rep air and lap aro-
Com pulsive preparation for operation is m and atory in scop ic ingu inal hernia rep airs, place the iliac and fem oral
patients w ith giant incisional hernias. All skin erosions vessels at risk for m ajor injury.
should be treated p rior to elective repair in ord er to red u ce
the risk of su bsequ ent infection. Pu lm onary function Nerve Injuries
should be op tim ized , inclu d ing sm oking cessation. Sm ok- Three nerves are exposed to inju ry d uring ingu inal hernia
ing is also a recognized im ped im ent to w ou nd healing. rep airs—the ilioingu inal, genitofem oral, and iliohypogas-
Weight loss is encou raged and m ed ically su pported . A tric nerves (Fig. 39.8). The ilioingu inal and genitofem oral
mu ltid iscip linary plan involving both general and plastic nerves are ad jacent to the sp erm atic cord and the iliohy-
su rgeons is often ap p lied . p ogastric runs w ithin the internal obliqu e mu scle of the
low er abd om inal w all. N erve transection u su ally resu lts in
Visceral Injuries self-lim iting groin or inner thigh anesthesia. N erve injury is
The bow el m ay be inju red d u ring the op ening or high liga- p resu m ably the mechanism for cases of d isabling postoper-
tion of an ind irect hernia sac. The comp lication is mini- ative p ain. Recent p rosp ective stu d ies rep ort a 29% inci-
mized by careful d issection and the id entification of groin d ence of chronic p ain follow ing ingu inal herniorrhap hy
stru ctu res and by inspection for slid ing com ponents. The (45–47). For these reasons, great care shou ld be exercised
blad d er m ay be inju red d u ring opening of a low er m id line d u ring d issections and rep airs to not inclu d e the nerves in
incisional hernia or the m ed ial extent of a d irect inguinal su tu re lines or at m esh or tack sites. If p ain d evelop s after
hernia. The p reop erative placem ent of a u rinary d rainage an initial recovery p eriod , a d eep sp ace abscess or d ehis-
catheter (Foley) m ay red uce the risk of blad d er inju ry. If the cence shou ld be consid ered . Withou t either of these tw o
blad d er is inju red , it shou ld be repaired and continu ou sly com p lications, m ost p ain resolves w ith su p p ortive m eas-
d rained w ith an ind w elling catheter u ntil a cystogram pro- u res only.
vid es p roof of healing. Postherniorrhap hy neu ralgia can becom e a d isabling
Enterocu taneou s fistu las are associated w ith com p lex cond ition. It is im p ortant to d eterm ine w h eth er th e
abd om inal w all d efects and large hernias. The presence of p atient had p ain p rior to hernia rep air, w hether p ostop -
knitted or w oven polypropylene or polyethylene m eshes erative p ain is the sam e in character as the p reop erative
app ears to increase the risk for d elayed enteric fistu liza- p ain, and w hen ingu inod ynia began. Most p osthernior-
tion. The p resence of m esh d u ring reop erative incisional rhap h y neu ralgia is the resu lt of p erineu ral fibrosis, a
hernia rep air increases the risk of u nintend ed bow el inju ry n orm al biological p rocess follow in g op eration. Delayed
d u e to the p resence of d ense ad hesions (8,9,51). Manage- n eu rom a p ain m ay be d u e to n erve con tact w ith a syn-
ment should be d irected tow ard control of the fistu la and thetic m esh; how ever, the available stu d ies su ggest that
metabolic su p p ort of the patient. Once the fistula has been m esh-associated ingu inod yn ia is n ot an ind ep end ent
FIGURE 39.8. The ilioinguinal,

genitofemoral, and iliohypogastric
nerves are exposed to injury during
inguinal hernia repairs. The ilioin-
guinal and genitofemoral nerves are
encountered posteriorly during a
Aorta preperitoneal inguinal hernia repair
Iliohypogastric nerve or within the spermatic cord. The ilio-
hypogastric nerve courses within the
internal oblique muscle of the lower
abdominal wall and is especially at
Ilioinguinal nerve risk for injury when tacks are placed
Poas major muscle below the inguinal ligament during a
laparoscopic inguinal hernia repair.
Genitofemoral nerve
Iliacus muscle
Iliohypogastric nerve
Ilioinguinal nerve
HRF '04
entity and the evid ence d oes not su p p ort clinical refer- the involved nerve d u e to its ad herence to the ap oneu rotic
ences to m esh-ind u ced chronic p ain synd rom e. Ap p arent tissu e of the groin is an im p ortant m echanism. Surgical
neu rom as associated w ith m esh exp lan ts h ave been therap y of p ostherniorrhap hy ingu inod ynia is m ost likely
observed in p atients w ith no p ain synd rom e w hen reop - to be su ccessfu l if the three involved nerves are resected .
erated for another reason, su ch as recu rrence. N eu rolysis is not recom m end ed . The ap p roach to the low er
The m ost com m on m echanism of ingu inal nerve inju ry abd om inal w all is p rep eritoneal via a low er m id line or
is failure to id entify and protect the three major groin high ingu inal incision. The entire lengths of the nerves
nerves exp osed d u ring herniorrhaphy. Lim ited d issection shou ld be resected as p roxim ally as p ossible to inclu d e the
w ithou t the id entification of all major stru ctu res of the involved segm ent and the num erous neural com m unica-
inguinal canal increases the risk of nerve inju ry and there- tions that exist betw een the three nerves. The transected
fore of chronic inguinod ynia. The external ring shou ld not p roxim al nerve end s are ligated and em bed d ed into the
be closed too tightly to prevent exposu re of the ilioingu inal internal obliqu e mu scle layer to red uce the incid ence of
nerve to the su ture line of the external obliqu e fascial clo- neu rom a form ation. Any su tu re, stap le, or alloplastic m esh
sure. The ilioingu inal nerve should not be extensively m aterial encou ntered along the length of the nerves is also
mobilized from the crem asteric layer in ord er to m inim ize excised . The com p lete rem oval of m esh d oes not appear to
inju ry to its neu rolem m al sheath. During the d issection of be necessary.
the su bcu taneou s ad ipose tissu e, early su rface branches of
the ilioingu inal and / or iliohyp ogastric nerves shou ld be Testicular Infarct
spared . Deep stap ling or tacking should be avoid ed d u ring Severe testicu lar p ain, sw elling, and ten d ern ess m ay
laparoscopic ingu inal hernia repair in ord er to prevent occu r after ingu in al h ern ia rep air, esp ecially if th e sp er-
entrap m ent of the iliohyp ogastric, genital (m ed ial to the m atic cord is skeletonized of m u scle an d fat or d ivid ed .
internal ring), and ilioingu inal (lateral to the internal ring) The risk is increased follow ing a reop eration u sing an
nerves. op en tech niqu e throu gh the scarred ingu in al can al.
When conservative measu res fail for at least 6 m onths, Orchiectom y is som etim es requ ired to resolve this com -
surgical therap y of neu ralgia m ay be consid ered . Su rgery is p lication. If obliteration of the internal ring is anticip ated ,
usu ally requ ired for perineural fibrosis, nerve entrap m ent su ch as d u ring the rep air of a m u ltip ly recu rrent ingu inal
by su tu re, stap le, or prosthetic d evice, and neuroma form a- h ernia, con sent for orch iectom y m ay be obtained . Du ring
tion. The triggering or aggravation of neu ropathic p ain by the d issection of fat and m u scle from the sp erm atic cord ,
w alking or d u ring hyp erextension of the hip and allevia- great care shou ld be u sed in p reservin g th e testicu lar
tion by rest and flexion of the thigh su ggest that traction of artery and vein.
Scrotal Hematoma incision. Exam p les inclu d e d ivision of the 12th intercostal
H em atom a in the scrotu m arises from sm all vessels w ithin nerve d u ring flank incision w ith rib resection.
the crem asteric m u scles. In the loose, areolar tissu e of the Wound Hematoma
scrotum , tam p onad e is m inim al. This com plication m ay be
avoid ed by m inim izing d issection of ind irect sacs off the Du ring ventral hernia rep air, the fascia is w id ely exp osed
sperm atic cord . Only the high p oint of the ind irect sac is and relaxing incisions are m ad e to m inim ize the hernia ring
mobilized for ligation of the internal ring. When a long area and to m axim ize the u se of au tologou s local tissu e
ind irect sac m u st be m obilized , as in a slid ing hernia, the transfers. The broad su bcu taneou s skin d issection pred is-
risk for a scrotal hem atom a m ay be red u ced by the u se of a p oses to w ou nd hem atom a formation. This p otential m an-
scrotal su p p ort after op eration. Prophylactic d rainage d oes d ates m eticu lou s hem ostasis d u ring op eration and
not prevent scrotal hem atom a form ation. closed -su ction d rainage u ntil d ischarge stop s. Surgical
When a scrotal hem atom a occu rs, it is usu ally d isp ersed techniqu es to red u ce tissu e d ead sp ace and the ap plication
betw een several layers of the repair and the sperm atic cord . of p ressu re d ressings m ay also help red u ce hem atom a for-
N eed le asp iration is therefore u su ally not help ful. Effective m ation.
evacu ation w ould requ ire reopening of the w ound and is Pulmonary Complications
necessary only for very large and tense hem atom as that
occur im m ed iately follow ing su rgery. Stable or d elayed Red u ction and rep air of large hernias m ay im p air p u l-
hem atom as m ay be m anaged w ith rest, w arm and cold m onary fu nction by inhibiting cou ghing d u e to the inci-
com presses, and close observation for continued bleed ing sional pain and by m echanically restricting d iaphragm atic
or infection, or both. excu rsion. The rep air of a giant hernia w ith the loss of
abd om inal d om ain m ay requ ire p rolonged ventilator
Chronic Abdominal Wall Wounds d ep end ence u ntil incisional p ain im p roves and the p eri-
Abd om inal w all w ou nd s m ay lead to chronic clinical toneal cavity accom m od ates its restored contents. The
com p laints, inclu d ing incisional p ain, p rotru sion, nu m b- im p lantation of an allograft m esh is often requ ired to m ini-
ness, or u nap p ealing ap p earance. An u nd erlying visceral m ize abd ominal cavity p ressu res. Peak airw ay pressu re
abnorm ality m u st first be exclu d ed . Qu estions m ay be intraop eratively may be u sed as a su rrogate m arker for ele-
raised abou t second ary gain, esp ecially in cases of chronic vated intraabd om inal pressu re d u ring abd om inal w all
p ain and d isability claim s (55,56). It is often help fu l to reconstru ction. There is grow ing evid ence that abd om inal
ed u cate p atients abou t the exp ected cou rse of su rgical w all reconstructive proced u res like com ponent separation
recovery, esp ecially as it relates to the p hases of w ou nd increase abd om inal volu m e follow ing the rep air of large
healing. For exam p le, p atients are often concerned abou t abd om inal w all d efects w ith the p rotection of p u lm onary
the color or m ass of scars. This anxiety m ay be red u ced by fu nction (57,58).
exp laining that the inflam m atory and p roliferative p hases
of tissu e rep air m ay last w eeks to m onths. Lap arotom y
p atien ts m ay d evelop a p rom inent “h ealing rid ge” as
■ REFERENCES
fascial scar p roliferation m axim izes 2 to 6 w eeks p ostop - 1. Du bay DA, Franz MG. Acu te w ou nd healing: the biology of acu te
w ou nd failu re. Surg Clin North Am 2003;83(3):463–481.
eratively. Som e p atients com plain of nu mbness below 2. N ational Center for H ealth Statistics. Detailed diagnoses and procedures,
transverse or obliqu e incisions. This occu rs as the resu lt of National Hospital Discharge Survey, 1995. H yattsville, MD: N ational
transected d istal sp inal nerves and u su ally becom es u nno- Center for H ealth Statistics; 1997.
3. Flu m DR, H orvath K, Koep sell T. H ave ou tcom es of incisional hernia
ticeable after several m onths. rep air im p roved w ith tim e? A p op u lation-based analysis. Ann Surg
Chronic pain in a scar may be difficult to explain and 2003;237(1):129–135.
treat. Prior to any intervention, an incisional hernia should be 4. Lu ijend ijk RW, H op WCJ, van d en Tol P, et al. A com p arison of su tu re
rep air w ith m esh rep air for incisional hernia. N Engl J Med 2000;343(6):
excluded by careful examination and noninvasive imaging. 392–398.
An intraperitoneal disord er is unlikely if the symptom is 5. Bu rger JW, Lu ijend ijk RW, H op WC, et al. Long-term follow -u p of a
reprod uced or aggravated by straining the muscles of the rand om ized controlled trial of sutu re versus m esh repair of incisional
hernia. Ann Surg 2004;240(4):578–583.
abdominal w all. Rarely, incisional pain is caused by ossifica- 6. Carlson MA. Acute w ou nd failu re. Surg Clin North Am 1997;77(3):
tion of the scar and relieved by excision of bony tissue, 607–636.
although heterotopic ossification notoriously recurs. Chronic 7. Jenkins TPN . The bu rst abd om inal w ou nd : a m echanical ap p roach. Br J
Surg 1976;63:873.
pain at the epigastrium may be due to injury to the xiphoid 8. Gray SH , Vick CC, Graham LA, et al. Risk of com p lications from
process during w ound closure. Rarely, excision of the enterotom y or unplanned bow el resection d uring elective hernia
xiphoid process relieves this source of discomfort. Underly- rep air. Arch Surg 2008;143(6):582–586.
9. H alm JA, d e Wall LL, Steyerberg EW, et al. Intrap eritoneal p olyp rop y-
ing fascial sutures that came close to the skin surface may lene m esh hernia repair com plicates subsequ ent abd om inal su rgery.
cause chronic pain, especially in thin patients. Ultimately, World J Surg 2007;31(2):423–429.
suture removal may be required. 10. Webster C, N eu m ayer L, Sm ou t R, et al. Prognostic m od els of abd om i-
nal w ou nd d ehiscence after lap arotom y. J Surg Res 2003;109:130–137.
Eccentric bu lging of the abd om inal w all m ay occu r 11. Etchells E, O’N eill C, Bernstein M. Patient safety in su rgery: error
w hen nerve or arterial su p p ly is severed d u ring su rgical d etection and p revention. World J Surg 2003;27(8):936–941.
12. Diaz JJ Jr, Gu y J, Berkes MB, et al. Acellu lar d erm al allograft for ventral 37. Lichtenstein IL, Shore JM. Sim p lified rep air of fem oral and recu rrent
hernia repair in the com p rom ised su rgical field . Am Surg 2006;72(12): inguinal hernias by a “p lu g” techniqu e. Am J Surg 1974;128:439–444.
1181–1187. 38. Stopp a RE. The treatm ent of com p licated groin and incisional hernias.
13. Diaz JJ Jr, Conqu est AM, Ferzoco SJ, et al. Mu lti-institu tional exp eri- World J Surg 1989;13(5):545–554.
ence using hu m an acellular d erm al m atrix for ventral hernia repair in a 39. N yhu s LM, Cond on RE, H arkins H N . Clinical exp erience w ith p rep eri-
com prom ised surgical field . Arch Surg 2009;144(3):209–215. toneal hernia rep air for all typ es of hernia of the groin. Am J Surg 1960;
14. Kim H , Bru en K, Vargo D. Acellu lar d erm al m atrix in the m anagem ent 100:234.
of high-risk abd om inal w all d efects. Am J Surg 2006;192(6):705–709. 40. Ferzli GS, Frezza EE, Pecoraro AM, et al. Prosp ective rand om ized
15. Best WR, Khu ri SF, Phelan M. Id entifying patient p reop erative risk fac- stu d y of stap led versu s u nstap led m esh in lap aroscop ic p rep eritoneal
tors and postoperative ad verse events in ad m inistrative d atabases: inguinal hernia rep air. J Am Coll Surg 1999;188(5):461–465.
resu lts from the Departm ent of Veterans Affairs N ational Surgical 41. Franz MG. The biological treatm ent of the hernia d isease. In:
Qu ality Im provem ent Program . J Am Coll Surg 2002;194(3):257–266. Schumpelick V, Fitzgibbons RJ, eds. Recurrent hernia. Heidelberg: Springer;
16. Burger JW, Lange JF, H alm JA, et al. Incisional hernia: early com plica- 2007:401–410.
tion of abd om inal su rgery. World J Surg 2005;29(12):1608–1613. 42. Pollock AV, N yhu s LM. Incisional hernias. In: Schw artz SI, Ellis H , ed s.
17. Merkow RP, Bilim oria KY, McCarter MD, et al. Effect of bod y m ass Maingot’s abdominal operations, 8th ed . N orw alk: Ap p leton-Centu ry-
ind ex on short-term ou tcom es after colectom y for cancer. J Am Coll Surg Crofts; 1985:335–350.
2009;208:53–61. 43. Ram irez OM, Ru as E, Dellon AL. Com p onents sep aration m ethod for
18. Pollock AV, Evans M. Early p red iction of late incisional hernias. Br J closu re of abd om inal w all d efects: an anatom ic and clinical stu d y. Plast
Surg 1989;76:953–954. Reconstr Surg 1990;86(3):519–526.
19. Franz MG. The biology of hernia form ation. Surg Clin North Am 2008; 44. Usher FC, Ochsner J, Tu ttle LL Jr. Use of Marlex m esh in the rep air of
88(1):1–15, vii. incisional hernias. Am Surg 1958;24(12):969–974.
20. Sm ith PD, Ku hn MA, Franz MG, et al. Initiating the inflam m atory 45. Bay-N ielsen M, Perkins FM, Kehlet H . Pain and fu nctional im p airm ent
phase of incisional healing p rior to tissu e inju ry. J Surg Res 2000;92(1): 1 year after ingu inal herniorrhap hy: a nationw id e qu estionnaire stu d y.
11–17. Ann Surg 2001;233(1):1–7.
21. Band a MJ, Dw yer KS, Beckm ann A. Wou nd flu id angiogenesis factor 46. Evans DS. Valu e of herniograp hy in the m anagem ent of occu lt hernia
stim u lates the d irected m igration of cap illary end othelial cells. J Cell and chronic groin pain in ad u lts. Br J Surg 2001;88(1):153–154.
Biochem 1985;29:183–193. 47. H air A, Paterson C, Wright D, et al. What effect d oes the d u ration of an
22. Ayd e B, Luna G. Incid ence of abd om inal w all hernia in aortic surgery. inguinal hernia have on p atient sym p tom s? J Am Coll Surg 2001;193(2):
Am J Surg 1998;175:400–402. 125–129.
23. H all KA, Peters B, Sm yth SH . Abd om inal w all hernias in p atients w ith 48. Chan STF, Esu fali ST. Extend ed ind ications for p olyp rop ylene m esh
abd om inal aortic aneu rysm versu s aortoiliac occlu sive d isease. Am J closu re of the abd om inal w all. Br J Surg 1986;73:3–6.
Surg 1995;170:572. 49. Molloy RG, Moran KT, Wald ron RP, et al. Massive incisional hernia:
24. Peacock J. Fascia and m u scle. In: Peacock J, ed . Wound repair, 3rd ed . abd om inal w all replacem ent w ith Marlex m esh. Br J Surg 1991;78(2):
Philad elphia, PA: W.B. Sau nd ers; 1984:332–362. 242–244.
25. Du nne JR, Malone DL, Tracy JK, et al. Abd om inal w all hernias: risk fac- 50. Klinge U, Klosterhalfen B, Mu ller M, et al. Foreign bod y reaction to
tors for infection and resou rce u tilization. J Surg Res 2003;111(1):78–84. m eshes u sed for the rep air of abd om inal w all hernias. Eur J Surg 1999;
26. H ou ck JP, Rypins EB, Sarfeh IJ, et al. Rep air of incisional hernia. Surg 165(7):665–673.
Gynecol Obstet 1989;169(5):397–399. 51. Kau fm an Z, Engelberg M, Zager M. Fecal fistu la: a late com p lication of
27. Tilson MD, Seashore MR. H u m an genetics of the abd om inal aortic Marlex m esh rep air. Dis Colon Rectum 1981;24(7):543–544.
aneu rysm . Surg Gynecol Obstet 1984;158:129–132. 52. Voyles CR, Richard son JD, Bland KI, et al. Em ergency abd om inal w all
28. Lehnert B, Wad ou h F. H igh coincid ence of ingu inal hernias and reconstruction w ith polypropylene m esh: short-term benefits versu s
abd om inal aortic aneu rysm s. Ann Vasc Surg 1992;6:134–137. long-term com p lications. Ann Surg 1981;194(2):219–223.
29. Leaper DJ, Gottru p F. Su rgical w ou nd s. In: Leap er DJ, H ard ing KG, 53. Cald irone MW, Rom ano M, Bozza F. Progressive p neu m op eritoneu m
ed s. Wounds: biology and management, 1st ed . Oxford : Oxford University in m anagem ent of giant incisional hernias. Br J Surg 1990;77:306–308.
Press; 1998:23–40. 54. Raynor RW, Del Geurcio LRM. The p lace for p neu m op eritoneu m in the
30. Rutled ge RH . The Coop er ligam ent rep air. Surg Clin North Am 1993; rep air of m assive hernia. World J Surg 1989;13:581–585.
73(3):471–485. 55. Salced o-Wasicek MC, Thirlby RC. Postop erative cou rse after ingu inal
31. Welsh DRJ, Alexand er MAJ. The Shou ld ice rep air. Surg Clin North Am herniorrhap hy. A case-controlled com p arison of p atients receiving
1993;73(3):451–469. w orker ’s com p ensation versus patients w ith com m ercial insurance.
32. N ilsson E, Kald A, And erberg B, et al. H ernia su rgery in a d efined pop - Arch Surg 1995;103(1):29–32.
u lation. A prospective three year au d it. Eur J Surg 1997;163:823–829. 56. Barku n JS, Keyser EJ, Wexler MJ, et al. Short-term ou tcom es in op en
33. Kald A, N ilsson E, And erberg B, et al. Reop eration as su rrogate end - versu s lap aroscop ic herniorrhap hy: confou nd ing im p act of w orker ’s
point in hernia su rgery: a three year follow -u p of 1565 herniorrhap hies. com pensation on convalescence. J Gastrointest Surg 1999;3(6):575–582.
Eur J Surg 1998;164:45–50. 57. Reilingh TSD, van Goor H , Rosm an C, et al. “Com p onents sep aration
34. H alstead WS. Surgical papers by William Stewart Halstead. Baltim ore, techniqu e” for the repair of large abd om inal w all hernias. J Am Coll
MD: Johns H opkins Press; 1924. Rep ort N o. 1. Surg 2003;196(1):32–37.
35. Lichtenstein IL, Shu lm an AG. Am bu latory ou tp atient hernia su rgery, 58. O’Mara MS, Papasavas PK, N ew ton ED, et al. Mod ified sep aration of
inclu d ing a new concep t. Int Surg 1986;71:1. parts as an intervention for intraabd om inal hyp ertension and the
36. Lichtenstein IL, Shu lm an AG, And erberg B. The tension-free hernio- abd om inal com p artm ent synd rom e in a sw ine m od el. Plast Reconstr
plasty. Am J Surg 1989;157:188. Surg 2004;114(7):1842–1845.
CHAPTER
40
Complications of Laparoscopic Surgery

J onathan F. Finks
■ INTRODUCTION The most commonly injured blood vessels are the inferior
epigastrics, usually during placement of a lateral trocar.
The origins of m od ern laparoscopic su rgery reach back Injury to these vessels has been reported in 0.2% to 2% of
over a centu ry. In 1902, Kelling p erform ed celioscop y to cases (1). While the superficial epigastric vessels can be seen
exam ine the abd om inal organs of d ogs u sing a cystoscop e w ith transillumination in nonobese patients, the deeper epi-
w ith a heated light sou rce at its d istal end . Since that tim e, gastrics cannot. One should attempt to visualize these vessels
trem end ou s ad vances in op tics, vid eo im aging, equ ip - laparoscopically and follow their course from the level of the
m ent, and techniqu es have m ad e lap aroscop ic su rgery inguinal ligament cephalad along the abdominal wall (2).
ap plicable to a broad array of abd om inal p roced ures. With Anatomic studies suggest that these vessels are typically
the increased u se of laparoscopy has com e an aw areness of located in an area between 4 and 8 cm from the midline and
significant comp lications associated w ith these techniqu es. ports should be placed lateral to this zone to prevent injury.
Und erstand ing how to prevent, recognize, and m anage Minor bleeding from the epigastrics can sometimes be con-
these com plications is critical to safe practice in laparo- trolled with d irect pressure. More significant bleeding can be
scopic su rgery. managed with tamponade by inserting the balloon from a
Foley catheter directly into the trocar site. Alternatively,
■ EARLY COMPLICATIONS bleeding can be controlled using full-thickness abdominal
w all suture ligation of the vessels. In cases of persistent bleed -
Early complications during laparoscopic surgery include ing, wound exploration may be required. Care should be
events that occur w hile obtaining access to the abd om inal taken to control even minor bleed ing from a port site, as post-
cavity and those related to the effects of pneumoperitoneum. operative abd ominal wall hematoma can lead to a significant
d rop in hematocrit. Observation of all lateral ports during
■ Access-related injuries removal from the abdominal wall at the end of a procedure
remains an important step in preventing this complication.
Access-related injuries are those that occu r d u ring estab- Major vascular injury is associated w ith a mortality rate
lishm ent of p neu m op eritoneu m or d u ring trocar p lace- of 9% to 17% (3) and typically occu rs d uring p lacement of
m ent and inclu d e inju ries to blood vessels of the abd om inal the initial trocar (54%) or at insertion of the Veress need le
w all, m esentery, or retroperitoneum as w ell as bow el, blad - (46%), most commonly at the umbilicu s (3,4). Very thin
d er, and other visceral structures. Reported rates of access- p atients are at particu lar risk for this comp lication, as the
related bow el inju ry range from 0.07% to 0.18%, w hile rates d istance betw een the abd om inal w all and the retroperi-
of m ajor vascu lar inju ry range from 0.04% to 0.09%. toneal vessels at the level of the um bilicu s m ay be as little as
Althou gh rare, access injuries accou nt for u p to half of all 2 cm in the anesthetized patient w ith muscle relaxation (4).
comp lications occu rring d u ring lap aroscop ic su rgery and The vessels m ost at risk for inju ry inclu d e the aorta (u su ally
can have d evastating consequences, inclu d ing hem or- at its bifu rcation), the iliac vessels (especially on the right),
rhage, sep sis, m u ltisystem organ failure, and d eath. Fu r- and the vena cava, although inju ry to mesenteric, omental,
therm ore, these inju ries account for a d isprop ortionate splenic, and liver vascu latu re has also been reported (2).
am ount of m ed ical liability claim s (1). Und erstand ing how The position of the aortic bifu rcation relative to the u m bili-
these inju ries occur and id entifying strategies to op tim ize cus is quite variable, ranging from 5 cm cephalad to 3 cm
safety at entry is essential to safe p ractice in laparoscop ic caud al to the u mbilicu s in the su pine position (5), and d oes
surgery. Measu res for avoid ing access-related com p lica- not correlate w ith bod y mass ind ex. The u mbilicu s is there-
tions are su m m arized in Table 40.1. fore an unreliable land mark for d etermining its location.
There are several m easu res that m ay be u tilized to
red u ce the risk for m ajor vascu lar inju ry. First, patients
m u st be com p letely relaxed p rior to insertion of the Veress
Jonathan F. Finks: University of Michigan, Ann Arbor, MI
need le and p rimary trocar, as contraction of the abd om inal
48109.
522
Chapter 40 • Complications of Laparoscopic Surgery 523
Table 4 0 .1 M ea su r es for avoid in g patients whose postoperative course w as complicated by

a ccess-r ela t ed com p lica t ion s infection, intraabd ominal abscess, or bowel obstruction, all
of w hich increase the likelihood of ad hesions. Over half of
Setup phase these injuries are not d etected at the time of operation and
• Maintain table height at waist level of the operating surgeon typically present w ithin 48 to 72 hours postoperatively (6,7),
• Keep patient in a neutral position often w ith abd ominal sepsis. Bow el injuries lead to laparo-
• Employ nasogastric decompression tomy in 60% of patients and are associated w ith a 2.5% to
• Ensure adequate abdominal wall relaxation
5% risk for mortality, mostly due to delayed presentation (3).
• Increase intra-abdominal pressure between 20 and 25 mm Hg prior to
There is no fool-proof method to eliminate the risk for
initial access
bow el inju ry. In patients at high risk for mid line ad hesions,
Initial access and placement of first trocar how ever, one should consid er left up per qu ad rant access by
• Use left upper quadrant (Palmer’s point) for initial entry in
placement of a Veress need le at Palmer ’s point, 3 cm below
• Very thin patients
the left costal margin in the mid clavicular line (7). There are
• Obese patients
• Patients with previous laparotomy several ad vantages to left u pp er qu ad rant access. First, this
• Elevate abdominal wall anteriorly before insertion of the Veress area is typ ically free from small bow el ad hesions (7). Ad d i-
needle and first trocar (may grasp fascia or umbilical stalk) tionally, the abd ominal w all is thinner here than at the
• Insert laparoscope as soon as insufflation is sufficient to allow umbilicu s, making access easier in obese patients (8). Fur-
visualization thermore, entry at this site also carries less risk for major
• Inspect the area beneath the initial entry site for vascular or visceral vascular injury than d oes an umbilical approach. For these
injury reasons, entry at Palm er ’s p oint is recom m end ed for obese
• Immediate conversion to open for patients, very thin p atients, and those w ith high risk for
• Blood on aspiration of the Veress needle ad hesions. Complete abd ominal w all relaxation and gastric
• Evidence of retroperitoneal hematoma
d ecompression are mand atory prior to left upper quad rant
Placement of secondary trocars access, and this approach shou ld be avoid ed in p atients
• Transilluminate abdominal wall to identify superficial epigastric vessels w ith hepatomegaly or splenom egaly d ue to the ad d ed risk
• Visualize the deep epigastric vessels laparoscopically for injury to these structures.
• Insert trocars in the midline or at least 8 cm lateral to the midline
There is no convincing evid ence to recom m end one
• Avoid angling lateral trocars toward the midline
access techniqu e over another. In a recent m eta-analysis,
• Laparoscopically, visualize each port during placement
there w as no d ifference in rates of m ajor vascu lar or vis-
Procedure end ceral injury betw een op en (H asson) and closed (Veress)
• Laparoscopically, visualize each lateral port during removal and inspect
techniqu es (4). The stu d y acknow led ged , how ever, that the
port site for bleeding
exam ined stud ies had sm all num bers and often exclu d ed
• Close the fascia of all ports with diameter 10 mm
high-risk p atients. Fu rtherm ore, earlier m eta-analyses sug-
gested that open entry w as associated w ith a higher rate of
bow el inju ry, w hile the closed techniqu e w as associated
mu scu lature w ill bring the abd om inal w all in closer contact w ith a higher rate of vascu lar inju ry. Given the rarity of the
to the retrop eritoneal stru ctu res. Also, it is generally recom - p rim ary ou tcom es, a d efinitive rand om ized trial to com -
mend ed to keep the patient in the su pine position d u ring p are the variou s access techniqu es w ou ld requ ire 10,000
placem ent of the Veress need le and / or trocars, as p lace- p atients in each stu d y arm and is u nlikely to occur (10,11).
ment into the Trend elenbu rg position often rotates the Recent ad vances in trocars have been touted to increase
sacral p rom ontory and aorta closer to the u m bilicu s. When op erative safety. These inclu d e rad ially exp and ing trocars
entering the abd om en at the um bilicus, the abd om inal w all w ith blu nt tip s, as w ell as op tical trocars that allow for
shou ld be lifted anteriorly. An effective w ay to accom p lish d irect visu alization of entry into the p eritoneal cavity.
this is to grasp and elevate the fascia or u m bilical stalk after While rad ially d ilating trocars have been show n to red u ce
the initial skin incision has been m ad e (6). Elevation of the p ort site bleed ing, neither these nor the op tical trocars have
abd om inal w all has been show n to su bstantially increase been show n to red u ce the risk for significant vascular or
the d istance betw een the abd om inal w all and the retrop eri- visceral inju ry (2,4,11,12). Rep orts of m ajor inju ry have
toneal stru ctu res (7,8). Increasing intraabd om inal p ressu re been associated w ith both typ es of trocars.
(IAP) to betw een 20 and 25 m m H g prior to p lacem ent of A basic principle of abdominal access is to maintain con-
the first trocar has also been show n to increase the d istance trolled insertion of the trocar. An essential but often over-
betw een the abd om inal w all and abd om inal contents w ith- looked aspect of controlled entry is attention to ergonomic
out significant hem od ynam ic effects (9,10). Finally, the area principles. As the table height increases relative to the operat-
beneath the initial entry site shou ld be inspected and all ing surgeon, the surgeon tends to compensate for the height
second ary trocars shou ld be p laced u nd er d irect vision to by abducting his or her arms; this is associated with a loss of
red u ce the risk for vascu lar or visceral inju ry. control of arm movement. The table should be placed at a
The risk for bowel injury is highest in those with abd om- height that is comfortable for the surgeon and that allows the
inal wall ad hesions from prior surgery, particularly in arms and should ers to remain relaxed w ith elbows close to
the body. This will allow for a smoother, more controlled tro- intravascu lar volum e statu s, d egree of hyp ercarbia, ventila-
car placement, with better control of the depth of insertion, tion strategy, and und erlying card iop ulmonary status. Most
stopping the thrust when the peritoneum is entered. stud ies su ggest that pneu moperitoneum, w ith an IAP 15
mm H g, lead s to elevations in systemic vascular resistance
(SVR) and mean arterial pressu re (MAP) w ith a concom i-
■ Effects of pneumoperitoneum tant d rop in card iac ou tp u t, largely d ep end ent on the
Lap aroscop ic surgery requires insu fflation of the abd om en p atient p osition (13–15). The com bined effects of anesthe-
w ith gas, typ ically carbon d ioxid e (CO 2), to facilitate exp o- sia, p neu m op eritoneu m and the reverse Trend elenbu rg
su re of the su rgical field . Creation of the pneu m op eri- p osition can red u ce card iac ou tp u t by as m u ch as 30% to
toneu m resu lts in increased IAP and absorp tion of large 50% (16–18). In otherw ise healthy p atients, this effect is
am ounts of CO 2 , both of w hich can have a significant u su ally only significant in the setting of hyp ovolem ia, as
im p act on hem od ynam ics, pulm onary m echanics, and the red u ction in venou s retu rn associated w ith the head -u p
acid –base statu s. Although pneu m operitoneum is w ell- p osition is com p ensated by the p neu m op eritoneu m in nor-
tolerated by m ost healthy patients, it can have a marked ly m ovolem ic p atients. When com bined w ith the Trend elen-
d etrim ental effect on those w ith u nd erlying card iop u l- bu rg p osition, p neu m op eritoneu m resu lts in a m arked
m onary d isease. The effects associated w ith p neum op eri- increase in venou s retu rn, w hich cou ld lead to congestive
toneum are su m marized in Table 40.2. heart failu re in p atients w ith u nd erlying heart d isease (12).
SVR can increase by as mu ch as 65% (11) and is related
Cardiovascular Effects to a nu m ber of factors, inclu d ing catecholam ine release (9),
The effect of pneumoperitoneum on hemodynamics depends com p ression of sp lanchnic cap illary bed s (10), and eleva-
on several factors, includ ing d egree of IAP, patient position, tions in p rod u ction of antid iu retic horm one and circu lating
levels of p lasm a renin and ald osterone (12). One stud y
id entified a four-fold increase in the levels of renin and
Table 4 0 .2 Effect s of ca r bon d ioxid e ald osterone follow ing p neu m op eritoneu m and head -up
p n eu m op er it on eu m p ositioning. Fu rtherm ore, the au thors fou nd that changes
in MAP w ere linearly correlated w ith changes in levels of
Cardiovascular
these neu rohormones (19). Whatever the cau se, the su b-
• Heart rate
• Bradycardia most common at insufflation stantial elevation in afterload can lead to increased m yocar-
• Sinus tachycardia secondary to catecholamine release d ial oxygen d emand . In p atients w ith u nd erlying card iac
• Cardiac contractility decreased d isease, this cou ld lead to m yocard ial ischem ia or even
• Cardiac output decreased infarction (20).
• Systemic vascular resistance increased There are several m easu res that m ay m itigate the hem o-
• Mean arterial pressure increased d ynam ic effects of p neu m op eritoneu m . First, su rgeons
• Central venous pressure increased shou ld ap p ly the least p ossible IAP necessary to p rovid e
Respiratory ad equ ate exp osu re. H em od ynam ic effects are d irectly p ro-
• Hypercarbia/acidosis portional to IAP and are minimal w hen IAP is kept 12 mm
• Elevation of the diaphragm H g (21–23). In ad d ition, p reop erative volu me load ing to
• Peak airway pressure increased achieve norm ovolem ia m ay help to m aintain card iac ou t-
• Functional residual capacity decreased p u t, p articu larly w hen the reverse Trend elenbu rg position
• Respiratory compliance decreased is anticip ated (24,25). Finally, u p w ard d isp lacem ent of the
• Intrapulmonary shunting increased
d iap hragm d u ring p neu m op eritoneu m lead s to elevated
• Alveolar–arterial gradient increased
intrathoracic pressu res and a rise in central venou s pres-
Vascular su re (CVP), p articu larly w hen p ositive end -expiratory
• Splanchnic bed compressed p ressu re is u sed . CVP m easu rem ents d o not correlate w ell
• Common femoral venous flow reduced
w ith card iac filling statu s. For that reason, p atients w ith
• Lower extremity venous pooling
significant u nd erlying card iac com p rom ise m ay benefit
Neurohormonal from m ore invasive hem od ynam ic m onitoring w ith a p u l-
• Catecholamine release m onary artery catheter and / or transesop hageal echocar-
• Aldosterone production increased
d iogram can help to op tim ize volu m e statu s (15,24).
• Elevation in plasma concentrations of
Card iac arrhythm ias are another com m on com p lication
• Renin
• Cortisol of p neu m op eritoneu m , rep orted in u p to 47% of patients
• Vasopressin u nd ergoing lap aroscop ic su rgery (16,17). Some arrhyth-
m ias, su ch as sinu s tachycard ia, are benign and occu r as a
Somatosensory
resu lt of an increase in circu lating catecholam ines. Others
• Peritoneal/diaphragmatic irritation
• Abdominal wall pain can occu r as a result of m yocard ial irritability related to
• Shoulder-tip pain hyp ercarbia (12). The m ost com m on and m ore d angerou s
arrhythm ias are brad yarrhythm ias, w hich inclu d e sinus
brad ycard ia, atrioventricu lar d issociation, and asystole. Table 4 0 .3 Ca u ses of a cu t e hyp oxia a n d
These resu lt from vagal stim u lation d u ring p eritoneal d is- h em odyn a m ic in st a bilit y d u r in g
tension, u su ally d uring initial insu fflation, and have been la p a r oscop ic su r ger y
rep orted in u p to 28% of patients (18). Fortunately, m ost of
these arrhythm ias can be su ccessfu lly m anaged w ith Comorbid conditions
release of p neu m operitoneu m and hyperventilation w ith a • Respiratory disease (chronic obstructive pulmonary disease)
FiO 2 of 1.0, althou gh vagolytics are som etim es requ ired • Morbid obesity
(12,13). They rarely recur w ith reinsu fflation. Ineffective ventilation
• Endotracheal tube obstruction
Respiratory System Effects • Massive subcutaneous emphysema
CO 2 is w id ely u sed for abd om inal insufflation becau se it is • Anesthesia circuit disconnect
inexp ensive, highly solu ble, rapid ly elim inated by the • Excessive intra-abdominal pressure/Trendelenburg position
lu ngs, and noncom bu stible (13). Du ring laparoscop ic su r- Intrapulmonary shunt
gery, CO 2 is rap id ly absorbed by the p eritoneal m em brane, • Endotracheal tube displacement (mainstem intubation)
resu lting in a nearly 50% increase in CO 2 ou tp ut (14). Som e • Pneumothorax/carbothorax
CO 2 w ill be absorbed by intracellu lar and p lasm a bu ffers. • Aspiration of gastric contents
Once these are saturated , progressive hypercapnia and aci- Diminished cardiac output
d osis can d evelop . • Myocardial depression/ischemia/infarction
H ypercapnia is exacerbated by the im pairm ent of respi- • Arrhythmia
ratory m echanics that resu lt from elevated IAP from insu f- • Venous gas embolism
• Hemorrhage
flation and by the Trend elenbu rg position. Both of these
• Hypovolemia
factors serve to red u ce p u lm onary com p liance and fu nc-
tional resid u al capacity, w hile elevating airw ay p ressu res Pericardial tamponade
(15). To overcom e these changes and restore eu cap nia,
m inu te ventilation mu st be increased by 12% to 16%
(17,18). In obese patients, resp iratory com pliance is fu rther
red u ced (26–28) and m inu te ventilation m ay need to be su rgery are listed in Table 40.3 (31). This d ifferential d iag-
increased by u p to 21% to avoid acid osis (29). nosis ap p lies to su d d en changes in hem od ynam ics and
While the excess CO 2 burd en is usu ally w ell-tolerated ETCO 2 as w ell.
in healthy p atients, those w ith u nd erlying card iop u l-
m onary d isease (Am erican Society of Anesthesiologists ■ INTRAOPERATIVE COMPLICATIONS
Class III or IV) m ay d evelop p ersistent hyp ercap nia and
acid osis d esp ite an increase in m inute ventilation. At p ar- This section consists of an overview of intraoperative com -
ticu lar risk are p atients w ith resp iratory com prom ise (e.g., p lications, inclu d ing vascu lar, gastrointestinal tract and
severe chronic obstru ctive pu lm onary d isease), d im inished u rinary tract inju ries, as w ell as card iop u lm onary com p li-
card iac fu nction, or an elevated m etabolic rate (e.g., cations su ch as venou s CO 2 em bolism , p neum othorax,
patients w ith sep sis) (9). In a stu d y of patients u nd ergoing p neu m om ed iastinu m , and su bcu taneou s em physem a. A
lap aroscop ic cholecystectom y, preoperative p u lm onary large prop ortion of intraoperative injuries are related to
fu nction tests revealing forced exp iratory volu m es 70% instru m entation, often in association w ith the use of elec-
of p red icted valu es and d iffu sion d efects 80% of p re- trocau tery. A d iscu ssion of com plications related to surgical
d icted valu es w ere risk factors for d evelop m ent of hyp er- stap lers and electrocau tery are also inclu d ed in this section.
cap nia and acid osis (24). In these high-risk p atients,
intraop erative arterial blood gas m onitoring of CO 2 levels ■ Urinary tract injury
is recom m end ed , as the end -tid al CO 2 (ETCO 2) w ill often
und erestimate the arterial partial pressure of CO 2 (PaCO 2), Bladder Injury
particu larly w hen the PaCO 2 is 41 m m H g (18). Strategies The incid ence of blad d er inju ries d uring laparoscopy sur-
for im p roving gas exchange in these p atients inclu d e m ini- gery is estim ated to be 0.02% to 8.3%, w ith inju ries to the
m izing IAP, u sing the head -up position w here p ossible to d om e accou nting for 90% of these inju ries (21). In a large
im p rove p u lm onary com pliance, and em ploying p ositive single-center series of blad d er inju ries, gynecologic opera-
end -exp iratory p ressu re (29,30). In som e p atients, conver- tions accou nted for 62% of all inju ries, w ith 26% occu rring
sion to an op en p roced u re m ay be requ ired . d u ring general su rgery p roced u res and 12% d uring u ro-
Desp ite the negative effects of abd om inal insu fflation logic p roced u res (16). Lap aroscop ically assisted vaginal
on p u lm onary m echanics and hyp ercap nia, hyp oxem ia hysterectom y is the m ost com m on op eration lead ing to
d u ring lap aroscop ic su rgery is relatively u ncom m on, p ar- blad d er inju ries, follow ed by p roced u res for end om etrio-
ticu larly in otherw ise healthy p atients (15,21,31), and its sis (3,17,21). The m ost com m on cau se of blad d er inju ries is
p resence shou ld p rom p t an im m ed iate search for its cau se. sharp d issection w ith electrocau tery (21). Risk factors for
The m ajor cau ses of acu te hyp oxia d u ring lap aroscop ic blad d er inju ry inclu d e ad hesions from p reviou s p elvic
operations and p elvic inflam m atory p rocesses. These broad ligam ent, p assing below the u terine vessels and
processes can be acu te, as seen w ith infection, or chronic, as entering the blad d er on its p osterolateral asp ect, ap p roxi-
seen w ith end om etriosis, m alignant infiltrative d isease, m ately 2.3 cm from the ed ge of the cervix. This region,
and previou s rad iation (18,21). near the u reterovesical ju nction, is the m ost com m on loca-
There are several m easu res that m ay help p revent blad - tion for inju ry d u ring gynecologic lap aroscop ic p roce-
d er inju ries. Placem ent of a Foley catheter d u ring p elvic d u res (28). As w ith blad d er inju ries, a com m on associated
proced u res w ill keep the blad d er d ecom pressed , m inim iz- risk factor is inflam m atory ad hesions lim iting visu aliza-
ing the chances for a trocar inju ry. Direct visu alization of tion d u ring the op eration.
the blad d er d om e is recom m end ed p rior to p lacem ent of Unlike blad d er inju ries, m ost u reteral inju ries (75% to
second ary trocars, although blad d er id entification is p ossi- 88%) are d iscovered p ostop eratively (32,34,36) and can
ble only in abou t 45% of patients, and visibility of the d om e p resent betw een 3 d ays and 2 m onths from the d ate of sur-
d im inishes w ith increasing BMI (18). In cases w here the gery. These d elayed inju ries typ ically p resent as fistu las
blad d er m u st be d issected off the anterior cervix and (u reterovaginal, u reterorectal, and u reterocu taneou s) w ith
vagina or off the anterior abd om inal w all, insu fflation of associated fever, hem atu ria, flank p ain, and / or p eritonitis
the blad d er w ith saline or even CO 2 can facilitate the d is- (32). Diagnosis is m ad e by excretory u rograp hy. If sus-
section (29). p ected intraop eratively, the integrity of the u reter should
In traop erative h em atu ria or p n eu m atu ria n oted in be confirm ed by retrograd e u reterocystograp hy.
th e Foley bag sh ou ld raise su sp icion for a blad d er in ju ry. Most u reteral inju ries, w hether d iscovered late or at the
In travesical instillation of betad yn e, m ethylen e blu e, or tim e of su rgery, w ill requ ire op erative rep air, as m ost stud -
ind igo carm ine can facilitate insp ection for leaks. Delayed ies have found sim ple stenting of u reteral lacerations to be
p resen tation of blad d er in ju ry m ay be accom p an ied by inad equ ate. By contrast, su ccess rates from u reteral rep air
fever, ileu s, abd om in al p ain, oligu ria, azotem ia, and u ri- top 94% (37). Distal injuries are best managed by reimplanta-
nary ascites (30). CT cystograp hy can aid in th e d iagn o- tion of the ureter into the blad d er. A psoas hitch can be used
sis. Pelvic flu id collection s sh ou ld be p ercu tan eou sly for injuries involving the entire low er third of the ureter. The
d rain ed , an d th e flu id sh ou ld be sen t for creatin in e ad d ition of an anterior blad d er flap m ay be required for
m easu rem ent. inju ries involving the d istal tw o-third s of the u reter.
Most blad d er injuries are recognized intraoperatively Another option for extensive injuries to the d istal half of
(16,17,32). These can often be repaired laparoscop ically, the ureter is a transureteroureterostomy, w hereby the injured
w ith a layered closure u sing absorbable su tu re (21). u reter is anastom osed to the contralateral u reter (or renal
Althou gh there are reports of laparoscopic closu re using p elvis). Lacerations to the p roxim al or m id u reter are best
staples, this is not cu rrently recomm end ed , both becau se of rep aired by p rim ary u reterou reterostom y, p erform ed over
the lack of clinical trials attesting to its effectiveness and a u reteral stent (16,38).
because of the risk of perm anent foreign bod ies in the blad -
d er w all, w hich can act as a nid us for calcu lus form ation or
recu rrent u rinary tract infections or may interfere w ith nor-
■ Gastrointestinal injury
m al contraction of the blad d er. Follow ing repair, a Foley The incid ence of bow el injury d uring laparoscopic su rgery
catheter is left in p lace for 7 to 10 d ays. Cystography to con- is estimated to be betw een 0.07% and 0.9% (39–41). Most of
firm closu re of the leak should be perform ed prior to these involve the sm all bow el (56%), inclu d ing the d u od e-
catheter rem oval. Long-term su ccess rates from blad d er nu m , or colon (39%) (42). The majority of bow el injuries not
repair are ap p roxim ately 98% (16). related to abd om inal access result from the use of electro-
cau tery (39,42,43). Most visceral inju ries are not d etected at
Ureteral Injury the tim e of op eration (39,43,44). Inju ries associated w ith
The incid ence of u reteral inju ries rep orted d u ring lap aro- d irect p erforation or blu nt force typ ically p resent w ithin 12
scop ic gynecologic su rgery ranges from 0% to 3.4% (32) to 36 hou rs, w hile those resu lting from electrotherm al
and d u ring general su rgery p roced u res ranges betw een inju ry p resent betw een 4 and 10 d ays after su rgery (44).
0% and 1.5% (22,23,25,33). As w ith blad d er inju ries, the Although som e patients w ill present w ith frank peritonitis
m ajority of u reteral inju ries (64%) resu lt from gynecologic and sep sis, m any w ill p resent w ith vagu e com plaints of
p roced u res, w ith 25% from general su rgery op erations d iscom fort, low -grad e fevers, and often only m ild labora-
and 11% follow ing u rologic p roced u res (34). The m ajority tory abnorm alities (39). For that reason, su rgeons shou ld
of u reteral inju ries occu r throu gh the u se of electro- have a high ind ex of su sp icion for the p resence of bow el
cau tery, follow ed by ligation, althou gh inju ries also occu r inju ry in p atients w ith abd om inal d iscom fort follow ing
throu gh cru shing and d evascu larization (26,32,35). Most lap aroscop ic p roced u res, even in the absence of frank peri-
u reteral inju ries in general su rgery follow colorectal tonitis and sepsis.
resection. Inju ries often occu r d u ring m obilization of the While inju ries id entified intraop eratively can often be
sigm oid colon, ligation of the inferior m esenteric vessels, managed laparoscopically, 80% of d elayed injuries require
or d ivision of the lateral rectal ligam ents (27). Low er in lap arotom y (39,45). If recognized at the tim e of su rgery,
the p elvis, the u reter cou rses m ed ially at the base of the m inor lacerations can be rep aired by oversew ing the
d efect, either lap aroscopically or open, d ep end ing u p on Minor vascu lar inju ries can be m anaged lap aroscop i-
the su rgeon’s com fort level. Electrocau tery inju ries create a cally in m ost cases. Inju ries to m ajor retrop eritoneal ves-
larger area of coagu lative necrosis, often w ell beyond w hat sels, how ever, shou ld p rom p t conversion to laparotom y.
is ap p arent initially. Anything beyond sup erficial elec- The first step is to ap p ly p ressu re to the bleed ing area w ith
trotherm al inju ries shou ld be treated w ith excision w ell a lap aroscop ic instru m ent or a sp onge, w hich can be
beyond the area of inju ry in ord er to prevent late p erfora- inserted throu gh a 10-m m trocar. A m id line laparotomy is
tion (44). then p erformed , w hile p ressu re is held via a lateral trocar.
A key p rincip le in avoid ance of gastrointestinal tract In general, the retrop eritoneu m shou ld not be op ened u ntil
inju ries d u ring laparoscop ic surgery is to keep sharp (e.g., the team (p referably inclu d ing a vascu lar su rgeon) is p re-
scissors) or “hot” (e.g., electrocau tery and u ltrasonic d is- p ared to gain p roxim al and d istal control of the injured ves-
sectors) instru m ents w ithin the visual field at all tim es. In sel. Good com m u nication w ith the anesthesiologist and the
ad d ition, bow el should be hand led gently w ithou t exces- op erating room staff is critical to ensu re that the p atient is
sive traction or torsion. Ad hesions should alw ays be d ivid ed ad equ ately resu scitated , blood p rod u cts are called for, and
sharp ly w ith scissors, and hem ostasis shou ld be achieved the necessary equ ip m ent and p ersonnel are m ad e available
w ith hem oclip s instead of electrocau tery, unless the bow el in an exped itiou s manner.
is w ell aw ay from the area of d issection. Finally, w hen
using stap lers or clip ap pliers, both sid es of the d evice ■ Pneumothorax, pneumomediastinum,
shou ld be clearly visu alized to p revent inad vertent inju ry
and subcutaneous emphysema
to nearby stru ctu res.
Subcutaneou s em physem a refers to the extravasation of
CO 2 into the su bcu taneou s tissu es. This can result from
■ Vascular injury m isp lacem ent of the Veress need le d u ring initial insu ffla-
Rep orted rates of vascu lar inju ry d u ring lap aroscop ic su r- tion or from d efects in the p eritoneu m . Subcutaneou s
gery range from 0.04% to 3.3%, w ith rates of m ajor vascu - em physem a is also significantly m ore com mon in cases of
lar inju ry betw een 0.04% and 0.1% (3,46–48). Althou gh extraperitoneal or retroperitoneal lap aroscopy than in
u ncom m on, vascu lar inju ries are the second lead ing cau se transabd om inal cases (53,54). Extrap eritoneal gas can
for m ortality follow ing laparoscopic proced ures and one of extend along fascial planes from the abd om en u p to the
the p rim ary cau ses for conversion to laparotom y (49,50). chest w all and neck, resu lting in p alp able crepitu s. From
Desp ite several d ecad es of exp erience w ith m inim ally the neck, gas can track d ow n into the chest and m ed i-
invasive techniqu es, hem orrhage rem ains a significant astinu m , resu lting in p neu m othorax and p neum om ed i-
com p lication of laparoscopic proced u res. This is d u e, at astinu m . Gas can also reach the thorax and m ed iastinu m
least in p art, to the expand ing ind ications for lap aroscop ic through congenital d efects or lacerations in the d iaphragm
surgery, w hich now includ e m ore com plex and high-risk or d u ring p roced u res involving the esop hageal hiatu s,
proced u res (51). su ch as hiatal hernia rep airs. While su bcu taneou s em phy-
In m ost series, access-related inju ries accou nt for the sem a is u su ally of little consequ ence, extensive bu ild u p can
greatest p rop ortion of m ajor vascu lar injuries, althou gh a significantly increase airw ay p ressu re and im p air ventila-
substantial p rop ortion of these injuries, and m ost m inor tion. The increased su rface area available for absorp tion of
vascu lar inju ries, result from m isuse of su rgical instru - CO 2 can also lead to hyp ercap nia and acid osis. Generally,
ments, u su ally in association w ith electrocautery (2,47,48, these sequelae resolve w ith d esu fflation of the abd om en.
51,52). Movem ent of an electrosurgical instrum ent ou tsid e Reinsu fflation at low er p ressu re m ay be requ ired (12).
the visu al field and inad vertent activation of the m onop o- CO 2 p neu m othorax can also resu lt from inad vertent
lar electrod e w ere com m only cited causes for inju ry in one inju ry to the m ed iastinal p leu ra and u su ally occu rs d u r-
series from a large nationw id e Sw iss registry (51). The ves- ing cases involving m ed iastinal d issection, su ch as op era-
sels m ost com m only inju red inclu d e the iliac vessels, aorta, tions for hiatal hernia, gastroesop hageal reflu x, and
inferior vena cava, and m esenteric vessels (52). Inju ries to achalasia. Su ch d efects can lead to tension p neu m othorax
hepatic, splenic, gastric, and om ental vessels have also been w ith an associated increase in airw ay p ressu res, ETCO 2,
rep orted . hyp oxia, and hem od ynam ic instability. Evid ence of p neu -
Most significant vascu lar inju ries are id entified intraop - m othorax inclu d es an acu te elevation in airw ay p ressu res
eratively. Vascu lar injuries beneath a thick om entu m or in and ETCO 2, visu alization of the lu ng p arenchym a, and
the retrop eritoneu m , how ever, m ay not be im m ed iately bu lging of the ip silateral d iap hragm . When p neu m otho-
app arent. Any su d d en d eterioration in the patient’s cond i- rax occu rs in this setting, the p leu ral d efect shou ld be
tion (i.e., hyp oxia, tachycard ia, and hypotension) shou ld be enlarged to help p revent tension p neu m othorax. To p re-
assu m ed to rep resent an occu lt vascu lar inju ry u ntil p roven vent sealing of the d efect d u ring insp iration, an 18-Fr red
otherw ise. Carefu l exam ination of the entire abd om en, ru bber catheter w ith sid e holes at its d istal end shou ld be
inclu d ing the m esentery, as w ell as the retroperitoneu m is p laced across the d efect. This w ill help equ alize p ressu res
w arranted . The sam e is true for blood seen on entry into across the d iap hragm . At the end of the p roced u re, the
the abd om en. p roxim al end of the tu be is p u lled ou t throu gh a 10-m m
p ort site. Follow ing d esu fflation, the p neu m othorax is leaks and , frequ ently, the need to convert to an op en proce-
evacu ated into a bow l of saline w hile the p atient is given a d u re (62). With regard to d ivision of heavily vascu larized
Valsalva breath (55). tissu e, su ch as m esentery, a failu re of the stap ling d evice in
a lap aroscop ic op eration inherently carries greater im m ed i-
ate risk to the p atient than the failu re of a tie or su tu re d u r-
■ Gas embolism ing an op en p roced u re. Lap aroscop ic stap ling d evices
Asym ptom atic gas em boli are com m on and have been d ivid e u p to 6 cm of tissu e at a tim e. This can result in a
id entified by transesophageal echocard iography in 69% of large bleed ing su rface if the d evice fails. In this setting,
patients u nd ergoing laparoscopic cholecystectom y (56) id entification and control of the offend ing vessel can be d if-
and 100% of p atients und ergoing total laparoscop ic hys- ficu lt to achieve lap aroscop ically.
terectom y (57). The incid ence of significant gas em bolism is Stap ler failu re is rep orted to occu r w ith a frequ ency of
mu ch low er, arou nd 0.0014%, but is associated w ith a m or- 1% to 1.7%, w ith p rim ary d evice failu re occu rring in 0.25%
tality rate of 28.5% (3). Given the high solubility of CO 2, to 0.3% of cases (62–64). This p roblem is likely u nd erre-
large am ou nts of this gas m ust enter the blood stream rap - p orted , as m ost su rgeons are likely to isolate the stapler
id ly for there to be any significant hem od ynam ic effect. and rep ort failu re only d u ring a seriou s event, su ch as d ur-
Most seriou s events have been associated w ith inad vertent ing the attem p t to stap le across a large vessel. Fu rtherm ore,
placem ent of th e Veress n eed le into an abd om inal w all w hat little evid ence there is su ggests that u ser error m ay be
vessel or the liver, w ith su bsequ ent insu fflation into a resp onsible for a su bstantial p rop ortion of stap ler failu res.
hep atic vein (12,58). Other cases have been associated w ith Deng et al. cond u cted an institu tional review and an
intraop erative inju ry to large veins, su ch as the hep atic analysis of the Food and Dru g Ad m inistration (FDA) d ata-
veins or IVC, frequ ently associated w ith the use of argon base involving stap ler m alfu nction (64). The au thors id enti-
beam coagu lation d u ring a laparoscopic proced ure (59–61). fied five cases of stap ler failu re from their institu tion
Su bstantially low er am ou nts of argon are requ ired to cau se am ong 460 lap aroscop ic cases and 55 rep orts of linear cut-
hem od yn am ic instability, given its low er solu bility in ting stap ler failu re since 1996 from the FDA d atabase.
blood . These w ere associated w ith a m ortality rate of 4%, an over-
CO 2 em bolism typ ically p resents w ith hyp oxia and a all m orbid ity rate of 45%, a transfu sion rate of 15%, and a
rap id d rop in ETCO 2, associated w ith signs of card iovas- conversion rate of 25%. In no case w here the d evice w as
cu lar collap se, inclu d ing hyp otension and tachycard ia or available for insp ection w as a p roblem id entified w ith the
brad ycard ia. Cyanosis of the head and neck m ay occu r as d evice itself. Preventable p roblem s inclu d ed the follow ing:
gas obstru cts the right ventricu lar ou tflow tract. Au scu lta- (a) incorp orating a p reviou sly p laced clip in the su tu re line;
tion of the heart w ith a transesop hageal or p record ial (b) u se of a p reviou sly fired stap ler cartrid ge; and (c) incor-
stethoscop e w ill reveal the classic grind ing “m ill-w heel” p oration of extra tissu e in the stap ler cartrid ge.
m u rm u r. Prom p t recognition and treatm ent are essential, There are several m easu res that can help p revent com -
as gas em bolism can rap id ly becom e fatal. Treatm ent p lications related to the u se of su rgical stap lers. A thorou gh
inclu d es release of the p neu m op eritoneu m and p lacem ent w orking know led ge of the d evice and fam iliarity w ith its
of the p atient into the left lateral d ecu bitu s p osition w ith u se are p aram ou nt. In the stu d y by Deng et al., the au thors
the head d ow n. This p osition facilitates trap p ing of noted that in several cases of stap ler m alfu nction, the sur-
rem aining gas w ithin the ap ex of the right ventricle. Venti- geon reported noticing an abnormal feel d u ring d eploy-
lation w ith a FiO 2 of 1.0 w ill hasten absorp tion of CO 2. m ent or op ening of the d evice (64). This find ing often
Finally, p lacem ent of a central venou s catheter w ill allow d enotes a m alfu nction and shou ld p rom p t the su rgeon to
for asp iration of any resid u al gas from the right ventricle stop d ep loym ent and m ake the necessary p rep arations for
(12,55,58). salvage, p articu larly w hen the d evice has been u sed to
d ivid e large vessels. Fu rtherm ore, it is im p ortant to ensure
that the tissu e to be d ivid ed is free of clip s or other foreign
■ Instruments bod ies, w hich cou ld interfere w ith the stap ler. Finally, it is
A d iscussion of com plications related to surgical instru - essential to ensu re that only the target tissu e is inclu d ed
ments is p articularly relevant to m inim ally invasive su r- w ithin the jaw s of the stap ler.
gery, given the increasing reliance of laparoscopic surgeons
on sop histicated equ ip m ent to p erform increasingly com - Electrocautery
plex op erations. In this section, w e w ill focu s on com p lica- Inju ries related to electrocau tery rem ain a lead ing source of
tions related to su rgical stap lers and electrocau tery. m orbid ity d u ring lap aroscop ic su rgery. Und erstand ing
how these inju ries occu r and how to p revent them is of crit-
Surgical Staplers ical imp ortance. There are fou r basic m echanism s of inju ry:
Few instrum ents are as essential to the p erform ance of insu lation failu re; d irect ap p lication; d irect cou p ling; and
com plex laparoscopic proced u res as su rgical staplers. cap acitive cou p ling. Breaks in the equ ip m ent insulation
Com p lications related to failure or m isuse of the d evice can resu lt in cu rrent leak to ad jacent instru ments, trocars,
includ e stap le line hem orrhage and leaks, anastomotic or viscera. Inju ries also occu r throu gh d irect ap p lication of
the active electrod e to an unintend ed target. This typ e of Propofol is associated w ith less PON V than inhalation
injury represents either inad equ acy of d issection technique anesthetics, bu t it is m ore d ifficu lt to titrate, potentially
or accid ental activation of the electrod e. Direct cou p ling increasing the risk for insu fficient anesthesia and associ-
refers to d irect contact betw een the active electrod e and a ated aw areness. Antagonists of the 5-H T3 receptor, su ch as
second cond u ctive instrum ent w ithin the abd om en, su ch od ansetron, are effective w hen ad m inistered at the end of
as a grasp er or even the laparoscope. Contact betw een the the proced u re and avoid m any of the sid e effects associated
second cond u ctor and bow el or other viscera (u su ally ou t- w ith trad itional antiemetics. Ad m inistration of IV d exam -
sid e of the visu al field ) lead s to occult injury. Finally, cap ac- ethasone has also been show n to red u ce PON V w ith few
itive cou pling occu rs w hen current is transferred from the sid e effects (68,69). Other recomm end ed strategies inclu d e
active electrod e throu gh insulation to an ad jacent cond u c- ensu ring ad equ ate hyd ration and avoid ing highly em eto-
tor (e.g., bow el) w ithout m aking d irect contact. An exam - genic anesthetics and analgesics in all patients w ith an ele-
ple of this typ e of coupling occu rs w ith the use of “m ixed ” vated risk for PON V (70).
trocars (p lastic sheath over m etal trocar). In this situ ation,
the p lastic sheath p revents d isp ersion of m onop olar cu r-
rent into the abd om inal w all, w here it cou ld be safely d is-
■ Pain
persed over a large area before retu rning to the grou nd ing An issue uniqu e to laparoscopic su rgery is postoperative
pad . Instead , cu rrent build s up betw een the m etal and the shou ld er p ain, w hich has been rep orted in 35% to 63% of
plastic, w ith the entire trocar acting as a capacitor. Cu rrent p atients (71). Prop osed mechanism s for this problem
can then d ischarge into ad jacent bow el or other viscera, inclu d e d iap hragm atic irritation from retained CO 2, as w ell
usu ally at the ju nction betw een the plastic sheath and the as stretch of the phrenic nerve as a result of pneumoperi-
metal trocar w ithin the abd om en (6,44). toneum. Convergence of sensory axons from the diaphragm
Part of the strategy for prevention of injuries from elec- and sensory axons from the should er on pain processing
trocau tery is to p rop erly m aintain equ ip m ent and assess neurons in the d orsal horn of C-4 and C-5 cervical segments
for breaks in insu lation prior to use. All op erating room s is the proposed basis for the referred pain (3). Several strate-
shou ld be equ ip p ed w ith u p d ated electrosu rgical acces- gies have d em onstrated proven efficacy in relieving shoul-
sory safety equ ip m ent, su ch as return electrod e m onitoring d er- tip pain follow ing laparoscopy. In a rand omized trial of
system s, w hich m easu re tissu e im ped ance and d isru p t the intraperitoneal irrigation of bupivacaine at the end of sur-
generator ou tp ut w henever a com prom ise in the current is gery, there w as a significant red uction in pain in the study
d etected . Fu rtherm ore, w henever the use of electrocau tery group versus the placebo group (71). Use of low -pressure
fails to achieve expected results at stand ard generator set- ( 12 m m H g) p neu m op eritoneu m has also been show n
tings, the su rgeon should assess for d efects in the grou nd to red u ce p ostop erative p ain, althou gh low IAP can also
plate or its connection or look for alternative p athw ays for red u ce exp osu re to the op erative field and m ay not be
the cu rrent, rather than sim ply d ialing u p the generator appropriate for all patients (72). In a randomized controlled
outp u t. In ad d ition, m ixed trocars shou ld be avoid ed to trial during aw ake laparoscopy, heating and humidifying
red u ce the risk for capacitive coup ling. Finally, a p riority the gas during insufflation decreased the incidence of shoul-
mu st be placed on keeping any instru m ent connected to an d er pain from 30% to 10% (73). Finally, forcible removal of
energy sou rce (electrocau tery, u ltrasonic d issector, etc.) CO 2 at the end of surgery by means of 30 degree Trendelen-
w ithin the field of vision at all tim es and avoid ing activa- burg position, in association w ith a pulmonary recruitment
tion of the “hot” end w hen it is ou tsid e the visu al field maneuver consisting of five manual breaths, w as show n to
(6,44). red uce shoulder pain and PONV after laparoscopic surgery
by 50% (74).
■ Port site hernia
■ Nausea/vomiting Port site hernias have been rep orted in 0.77% to 3% of
N au sea is estim ated to occur in 20% to 30% of patients in lap aroscop ic p roced u res and are associated w ith sm all
the im m ed iate p ostoperative period and in up to 60% of bow el obstru ction second ary to a Richter type of hernia
patients at som e tim e d u ring their hospital stay follow ing d efect (75). The incid ence of p ort site hernias is d irectly
lap aroscop ic su rgery (65). The etiology of postop erative related to the size of the fascial d efect created . In one stud y
nau sea in lap aroscopic surgery is controversial. Som e p roof gynecologic lap aroscop ic p roced u res, 86% of p ort site
posed m echanism s for nau sea inclu d e stretch of vagal hernias occu rred at sites w here p orts w ith d iam eter 10
nerve fibers, as w ell as elevated intracranial p ressu re m m had been u sed and only 2.7% occu rred in sites w here
resu lting from CO 2-ind u ced d ilation of cerebral vessels p orts w ith d iameter 8 m m had been p laced (76). Fascial
(12). Risk factors associated w ith postop erative nau sea and closu re shou ld be p erform ed at all p orts w ith d iam eter
vom iting (PON V) inclu d e fem ale gend er, a history of 10 m m . In one stu d y of p atients u nd ergoing colectom y,
m otion sickness or PON V, nonsm oking status, d u ration of rates of w ou nd infection (13.5% vs. 11%) an d hernia (24%
su rgery over 1 hour, and postop erative opioid u se (66,67). vs. 17%) w ere sim ilar betw een lap aroscop ic and op en
p roced u res (77). Fu rtherm ore, 86% of hernias and 80% of w hich have tou ched m alignant tissu e, and the abd om inal
w ou nd infections in the lap aroscop ic grou p occu rred at the w all.
specimen extraction site. This highlights the im p ortance of
w ou nd p rotection and m eticu lou s closu re techniqu e at
sites of sp ecim en extraction.
■ Conclusion
The ap p lication of lap aroscop ic techniqu es to a w id e vari-
ety of com p lex p roced u res has p rovid ed significant bene-
■ Port site recurrence fits to p atients in term s of red u ced p ostop erative p ain,
Early rep orts of high rates of port site m etastasis follow ing shorter recovery p eriod s, im p roved cosm esis, and low er
oncologic resection raised concerns abou t the safety of rates of w ou nd com p lications. H ow ever, there are also
laparoscop ic oncologic p roced ures (78,79). Since that tim e, nu m erou s com p lications u niqu e to lap aroscop ic su rgery.
nu m erou s investigators have sou ght to d eterm ine w hat Su rgeons and other m em bers of the healthcare team
effect the lap aroscop ic approach has on tum or biology and shou ld have a thorou gh u nd erstand ing of the p hysiologic
specifically on the incid ence of port site recu rrence. There changes and ad verse effects associated w ith CO 2 p neu -
are several p rop osed m echanism s for port site recurrence: m op eritoneu m . Su rgeons m u st also be m ind fu l of som e of
(a) increased exfoliation of tum or cells d uring laparoscopic the p itfalls of the lap aroscop ic ap p roach. Excellent visu ali-
manip u lation w ith su bsequ ent aerosolization of tu m or zation is alw ays requ ired , and instru m ents, p articularly
cells, w hich can leak arou nd trocars along w ith escap ing those associated w ith energy sou rces, m u st be kep t in the
gas in w hat has been d escribed as a “chim ney effect;” visu al field at all tim es. Finally, the su rgeon shou ld alw ays
( b) d irect contact betw een tu m or cells and the abd om inal be w illing to convert to an op en ap p roach w henever the
w all d u e to the sm all size of the incisions; (c) tissu e trau m a safety of p roceed ing lap aroscop ically is in d ou bt. Conver-
at p ort sites; (d ) tu m or con tam in ation of instru m ents, sion to an op en p roced u re shou ld not be consid ered a com -
w hich then com e in contact w ith the port site w ou nd s, and p lication of the p roced u re, bu t rather an exercise of sou nd
(e) d etrim en tal effects of CO 2 p neu m op eritoneu m on ju d gm ent.
im m u ne fu nction (78,80,81).
The resu lts from in vivo and in vitro stu d ies have been
conflicting, as som e stu d ies have suggested that aerosoliza-
■ REFERENCES
tion is not the m echanism for port site recurrence and that 1. Saber AA, Meslem ani AM, Davis R, et al. Safety zones for anterior
abd om inal w all entry d u ring laparoscopy: a CT scan m ap ping of ep i-
port site m etastasis d oes not requ ire CO 2 pneu m op erigastric vessels. Ann Surg 2004;239(2):182–185.
toneu m (78,82–84). This latter point is su pported by the 2. Makai G, Isaacson K. Com p lications of gynecologic lap aroscop y. Clin
find ing that p ort site recu rrence has been rep orted in thora- Obstet Gynecol 2009;52(3):401–411.
3. Magrina JF. Com p lications of lap aroscop ic su rgery. Clin Obstet Gynecol
coscop ic cancer resections, w here CO 2 is not used (85). Fu r- 2002;45(2):469–480.
therm ore, m ore recent clinical stud ies have d em onstrated 4. Ahm ad G, Du ffy JM, Phillip s K, et al. Lap aroscop ic entry techniqu es.
that port site recu rrence after laparoscopic cancer resection Cochrane Database Syst Rev 2008(2):CD006583.
5. N ezhat F, Brill AI, N ezhat CH , et al. Lap aroscop ic ap p raisal of the
is com p arable to w ou nd recu rrence after open surgery, p ar- anatom ic relationship of the u m bilicu s to the aortic bifu rcation. J Am
ticularly in the setting of colon cancer (86–89). Lap aroscop y Assoc Gynecol Laparosc 1998;5(2):135–140.
is also consid ered safe in cases of early ovarian cancer, 6. Philosophe R. Avoid ing com p lications of lap aroscop ic su rgery. Fertil
Steril 2003;80(Su pp l 4):30–39; qu iz 54–56.
as the vast m ajority of port site m etastases w ith ovarian 7. Molloy D, Kaloo PD, Coop er M, et al. Lap aroscop ic entry: a literatu re
cancer occur in the setting of ad vanced d isease and carci- review and analysis of techniqu es and com p lications of p rim ary p ort
nom atosis (90,91). With regard to gallblad d er cancer, how - entry. Aust N Z J Obstet Gynaecol 2002;42(3):246–254.
8. Tulikangas PK, N icklas A, Falcone T, et al. Anatom y of the left u p p er
ever, the general consensus is that an op en approach is qu ad rant for cannu la insertion. J Am Assoc Gynecol Laparosc 2000;7(2):
w arranted , given high rates of port site m etastasis and con- 211–214.
cerns abou t p erforation d uring laparoscop ic resection. If a 9. Grabow ski JE, Talam ini MA. Physiological effects of p neu m op eri-
toneum . J Gastrointest Surg 2009;13(5):1009–1016.
gallblad d er cancer is d iagnosed after the com pletion of a 10. Ishizaki Y, Band ai Y, Shim om u ra K, et al. Changes in sp lanchnic blood
laparoscop ic cholecystectom y, the port sites shou ld be flow and card iovascu lar effects follow ing p eritoneal insu fflation of car-
excised (92,93). bon d ioxid e. Surg Endosc 1993;7(5):420–423.
11. Joris JL, N oirot DP, Legrand MJ, et al. H em od ynam ic changes d u ring
Desp ite the lack of conclu sive evid ence regard ing the lap aroscop ic cholecystectom y. Anesth Analg 1993;76(5):1067–1071.
etiology of port site recu rrence d u ring lap aroscopic sur- 12. H enny CP, H ofland J. Lap aroscopic surgery: p itfalls d ue to anesthesia,
gery, there are several steps one should take to m inim ize positioning, and pneum op eritoneum . Surg Endosc 2005;19(9):1163–1171.
13. Tsereteli Z, Terry ML, Bow ers SP, et al. Prosp ective rand om ized clinical
the risk of this seriou s com plication. First d esu fflation trial com paring nitrou s oxid e and carbon d ioxid e pneum operitoneum
episod es should be kept to a m inim um d u ring the proce- for lap aroscopic su rgery. J Am Coll Surg 2002;195(2):173–179; d iscu ssion
d u re. Consid eration should be given to leaving all of the 9–80.
14. Kazam a T, Iked a K, Kato T, et al. Carbon d ioxid e ou tp u t in lap aroscop ic
ports in the abdomen until the pneumoperitoneum has been cholecystectom y. Br J Anaesth 1996;76(4):530–535.
released at the end of the procedure, although this step may 15. Sharm a KC, Brand stetter RD, Brensilver JM, et al. Card iop u lm onary
increase the risk for missed port site hemorrhage. Tumor physiology and pathop hysiology as a consequence of laparoscop ic sur-
gery. Chest 1996;110(3):810–815.
m anip u lation sh ou ld be m inim ized , and su rgeon s sh ou ld 16. Arm enakas NA, Pareek G, Fracchia JA. Iatrogenic bladd er perforations:
avoid d irect contact betw een contam inated instru m ents, longterm follow up of 65 patients. J Am Coll Surg 2004;198(1):78–82.
17. Said i MH , Sad ler RK, Vancaillie TG, et al. Diagnosis and m anagem ent 46. Larobina M, N ottle P. Com p lete evid ence regard ing m ajor vascu lar
of seriou s urinary com p lications after m ajor op erative laparoscop y. inju ries d u ring lap aroscop ic access. Surg Laparosc Endosc Percutan Tech
Obstet Gynecol 1996;87(2):272–276. 2005;15(3):119–123.
18. H urd WW, Am esse LS, Gru ber JS, et al. Visu alization of the ep igastric 47. Opitz I, Gantert W, Giger U, et al. Bleed ing rem ains a m ajor com p lica-
vessels and blad d er before lap aroscop ic trocar p lacem ent. Fertil Steril tion d uring laparoscopic su rgery: analysis of the SALTS d atabase. Lan-
2003;80(1):209–212. genbecks Arch Surg 2005;390(2):128–133.
19. O’Leary E, Hu bbard K, Torm ey W, et al. Laparoscopic cholecystectom y: 48. Roviaro GC, Varoli F, Sagu atti L, et al. Major vascu lar inju ries in lap aro-
haemod ynam ic and neuroend ocrine responses after pneum operi- scopic su rgery. Surg Endosc 2002;16(8):1192–1166.
toneu m and changes in position. Br J Anaesth 1996;76(5):640–644. 49. Bred a A, Veale J, Liao J, et al. Com p lications of lap aroscop ic living
20. Westerband A, Van De Water J, Am zallag M, et al. Card iovascular d onor nep hrectom y and their m anagem ent: the UCLA exp erience.
changes d uring laparoscopic cholecystectom y. Surg Gynecol Obstet 1992; Urology 2007;69(1):49–52.
175(6):535–538. 50. Richstone L, Seid em an C, Bald inger L, et al. Conversion d u ring lap aro-
21. Ostrzenski A, Ostrzenska KM. Blad d er inju ry d u ring lap aroscop ic su r- scopic surgery: frequency, ind ications and risk factors. J Urol 2008;180(3):
gery. Obstet Gynecol Surv 1998;53(3):175–180. 855–859.
22. Chahin F, Dw ived i AJ, Param esh A, et al. The im p lications of lighted 51. Schafer M, Lau p er M, Krahenbu hl L. A nation’s exp erience of bleed ing
ureteral stenting in lap aroscop ic colectom y. JSLS 2002;6(1):49–52. com p lications d uring lap aroscop y. Am J Surg 2000;180(1):73–77.
23. Kockerling F, Rose J, Schneid er C, et al. Lap aroscop ic colorectal anasto- 52. Chap ron CM, Pierre F, Lacroix S, et al. Major vascu lar inju ries d u ring
m osis: risk of p ostop erative leakage. Resu lts of a m u lticenter stu d y. gynecologic lap aroscop y. J Am Coll Surg 1997;185(5):461–465.
Lap aroscopic Colorectal Su rgery Stu d y Grou p (LCSSG). Surg Endosc 53. Saggar VR, Singhal A, Singh K, et al. Factors influ encing d evelop m ent
1999;13(7):639–644. of subcutaneous carbon d ioxid e em physem a in laparoscopic totally
24. Wittgen CM, N au nheim KS, And ru s CH , et al. Preop erative pu lm onary extraperitoneal ingu inal hernia rep air. J Laparoendosc Adv Surg Tech A
fu nction evaluation for lap aroscop ic cholecystectom y. Arch Surg 1993; 2008;18(2):213–216.
128(8):880–885; d iscu ssion 5–6. 54. Zhao LC, H an JS, Loeb S, et al. Thoracic com p lications of u rologic
25. Larach SW, Patankar SK, Ferrara A, et al. Com p lications of lap aro- lap aroscopy: correlation betw een rad iographic find ings and clinical
scopic colorectal su rgery. Analysis and com p arison of early vs. latter m anifestations. J Endourol 2008;22(4):607–614.
exp erience. Dis Colon Rectum 1997;40(5):592–596. 55. Hunter JG, Jobe BA. Minimally invasive surgery, robotics and natural ori-
26. Oh BR, Kw on DD, Park KS, et al. Late p resentation of u reteral injury fice transluminal endoscopic surgery. In: Brunicardi FC, Andersen DK,
after lap aroscop ic su rgery. Obstet Gynecol 2000;95(3):337–339. Billiar TR, et al., eds. Schwartz’s principles of surgery, 9th ed. New York, N Y:
27. Cass AS, Bubrick MP. Ureteral inju ries in colonic su rgery. Urology 1981; McGraw H ill; 2009. Available at http :/ / w w w.accesssu rgery.com / con-
18(4):359–364. tent.asp x?aID 5014248, accessed Janu ary, 2010.
28. Kalisvaart JF, Finley DS, Ornstein DK. Robotic-assisted rep air of iatro- 56. Derou in M, Cou tu re P, Bou d reau lt D, et al. Detection of gas em bolism
genic ureteral ligation follow ing robotic-assisted hysterectom y. JSLS by transesop hageal echocard iograp hy d u ring lap aroscop ic cholecys-
2008;12(4):414–416. tectom y. Anesth Analg 1996;82(1):119–124.
29. O’H anlan KA. Cystosu fflation to p revent blad d er inju ry. J Minim Inva- 57. Kim CS, Kim JY, Kw on JY, et al. Venou s air em bolism d u ring total
sive Gynecol 2009;16(2):195–197. laparoscopic hysterectom y: com parison to total abd om inal hysterec-
30. Tai CK, Li SK, Hou SM, et al. Blad der injury mimicking acute renal fail- tom y. Anesthesiology 2009;111(1):50–54.
ure after cesarean section: a d iagnostic challenge and minimally invasive 58. Joshi GP. Com p lications of lap aroscop y. Anesthesiol Clin North America
management. Surg Laparosc Endosc Percutan Tech 2008;18(3):301–303. 2001;19(1):89–105.
31. O’Malley C, Cu nningham AJ. Physiologic changes d u ring lap aroscop y. 59. Abu t YC, Eryilm az R, Okan I, et al. Venou s air em bolism d u ring lap aro-
Anesthesiol Clin North America 2001;19(1):1–19. scop ic cholecystectom y. Minim Invasive Ther Allied Technol 2009;18(6):
32. Leonard F, Fotso A, Borghese B, et al. Ureteral com p lications from 366–368.
laparoscopic hysterectom y ind icated for benign uterine pathologies: a 60. Ikegam i T, Shim ad a M, Im u ra S, et al. Argon gas em bolism in the ap p li-
13-year experience in a continu ou s series of 1300 p atients. Hum Reprod cation of lap aroscop ic m icrow ave coagu lation therap y. J Hepatobiliary
2007;22(7):2006–2011. Pancreat Surg 2009;16(3):394–398.
33. Regad as FS, Rod rigu es LV, N icod em o AM, et al. Com p lications in 61. Min SK, Kim JH, Lee SY. Carbon d ioxide and argon gas embolism d uring
lap aroscopic colorectal resection: m ain typ es and p revention. Surg laparoscopic hepatic resection. Acta Anaesthesiol Scand 2007;51(7):949–953.
Laparosc Endosc 1998;8(3):189–192. 62. Sim p er SC, Erzinger JM, Sm ith SC. Com p arison of lap aroscop ic linear
34. Parp ala-Sp arm an T, Paananen I, Santala M, et al. Increasing num bers of stap lers in clinical p ractice. Surg Obes Relat Dis 2007;3(4):446–450; d is-
ureteric inju ries after the introd u ction of lap aroscop ic su rgery. Scand J cu ssion 50–51.
Urol Nephrol 2008;42(5):422–427. 63. Chan D, Bishoff JT, Ratner L, et al. End ovascu lar gastrointestinal sta-
35. Tsujinaka S, Wexner SD, DaSilva G, et al. Prophylactic u reteric catheters p ler d evice m alfu nction d u ring laparoscop ic nephrectom y: early
in laparoscopic colorectal surgery. Tech Coloproctol 2008;12(1):45–50. recognition and m anagem ent. J Urol 2000;164(2):319–321.
36. H ove LD, Bock J, Christoffersen JK, et al. Analysis of 136 u reteral 64. Deng DY, Meng MV, N gu yen H T, et al. Lap aroscop ic linear cu tting sta-
injuries in gynecological and obstetrical surgery from com pleted insur- p ler failure. Urology 2002;60(3):415–419; d iscu ssion 9–20.
ance claim s. Acta Obstet Gynecol Scand 2010;89(1):82–86. 65. Brad shaw WA, Gregory BC, Finley CR, et al. Frequ ency of p ostop era-
37. De Cicco C, Ret Davalos ML, Van Cleynenbreu gel B, et al. Iatrogenic tive nau sea and vom iting in p atients u nd ergoing lap aroscop ic foregu t
ureteral lesions and rep air: a review for gynecologists. J Minim Invasive su rgery. Surg Endosc 2002;16(5):777–780.
Gynecol 2007;14(4):428–435. 66. Ap fel CC, Laara E, Koivu ranta M, et al. A sim p lified risk score for p re-
38. Tam u ssino KF, Lang PF, Breinl E. Ureteral com p lications w ith op era- d icting p ostop erative nau sea and vom iting: conclu sions from cross-
tive gynecologic lap aroscop y. Am J Obstet Gynecol 1998;178(5):967–970. valid ations betw een tw o centers. Anesthesiology 1999;91(3):693–700.
39. Bishoff JT, Allaf ME, Kirkels W, et al. Lap aroscop ic bow el inju ry: inci- 67. Koivu ranta M, Laara E, Snare L, et al. A su rvey of p ostop erative nau sea
d ence and clinical p resentation. J Urol 1999;161(3):887–890. and vom iting. Anaesthesia 1997;52(5):443–449.
40. Kw on AH , Inui H , Kam iyam a Y. Lap aroscop ic m anagem ent of bile 68. Ap fel CC, Korttila K, Abd alla M, et al. A factorial trial of six interven-
d u ct and bow el inju ry d u ring lap aroscop ic cholecystectom y. World J tions for the p revention of p ostop erative nau sea and vom iting. N Engl J
Surg 2001;25(7):856–861. Med 2004;350(24):2441–2451.
41. Schrenk P, Woisetschlager R, Rieger R, et al. Mechanism , m anagem ent, 69. Sm ith I. Anesthesia for lap aroscop y w ith em p hasis on ou tp atient
and p revention of lap aroscop ic bow el inju ries. Gastrointest Endosc 1996; laparoscop y. Anesthesiol Clin North America 2001;19(1):21–41.
43(6):572–574. 70. White PF, Sacan O, N uangcham nong N , et al. The relationship betw een
42. van d er Voort M, H eijnsd ijk EA, Gou m a DJ. Bow el inju ry as a com pli- p atient risk factors and early versu s late postoperative em etic sym p -
cation of lap aroscop y. Br J Surg 2004;91(10):1253–1258. tom s. Anesth Analg 2008;107(2):459–463.
43. El-Banna M, Abd el-Atty M, El-Meteini M, et al. Managem ent of laparo- 71. Cu nniffe MG, McAnena OJ, Dar MA, et al. A p rosp ective rand om ized
scopic-related bow el inju ries. Surg Endosc 2000;14(9):779–782. trial of intraop erative bup ivacaine irrigation for m anagem ent of shoul-
44. Wu MP, Ou CS, Chen SL, et al. Com p lications and recom m end ed p rac- d er-tip pain follow ing lap aroscop y. Am J Surg 1998;176(3):258–261.
tices for electrosu rgery in lap aroscop y. Am J Surg 2000;179(1):67–73. 72. Gu ru sam y KS, Sam raj K, David son BR. Low p ressu re versu s stand ard
45. Chap ron C, Pierre F, H archaou i Y, et al. Gastrointestinal injuries d u ring p ressu re pneu m operitoneum in laparoscopic cholecystectom y. Cochrane
gynaecological lap aroscop y. Hum Reprod 1999;14(2):333–337. Database Syst Rev 2009;(2):CD006930.
73. Dem co L. Effect of heating and hu m id ifying gas on p atients u nd ergo- 84. Wittich P, Marqu et RL, Kazem ier G, et al. Port-site m etastases after
ing aw ake laparoscopy. J Am Assoc Gynecol Laparosc 2001;8(2):247–251. CO(2) laparoscopy. Is aerosolization of tu m or cells a p ivotal factor?
74. Phelp s P, Cakm akkaya OS, Ap fel CC, et al. A sim p le clinical m aneuver Surg Endosc 2000;14(2):189–192.
to red uce laparoscop y-ind uced should er pain: a rand om ized controlled 85. Chen TP, Liu H P, Lu H I, et al. Incid ence of incisional recu rrence after
trial. Obstet Gynecol 2008;111(5):1155–1160. thoracoscop y. Surg Endosc 2004;18(3):540–542.
75. Philip s PA, Am aral JF. Abd om inal access com p lications in lap aroscopic 86. Clinical Ou tcom es of Su rgical Therap y Stu d y Grou p . A com p arison of
su rgery. J Am Coll Surg 2001;192(4):525–536. lap aroscopically assisted and op en colectom y for colon cancer. N Engl J
76. Montz FJ, H olschneid er CH , Mu nro MG. Incisional hernia follow ing Med 2004;350(20):2050–2059.
laparoscopy: a survey of the Am erican Association of Gynecologic 87. Buu nen M, Veld kam p R, H op WC, et al. Su rvival after lap aroscop ic
Lap aroscopists. Obstet Gynecol 1994;84(5):881–884. surgery versu s open surgery for colon cancer: long-term ou tcom e of a
77. Winslow ER, Fleshm an JW, Birnbau m EH , et al. Wou nd com p lications rand om ised clinical trial. Lancet Oncol 2009;10(1):44–52.
of laparoscop ic vs op en colectom y. Surg Endosc 2002;16(10):1420–1425. 88. Lacy AM, Delgad o S, Garcia-Vald ecasas JC, et al. Port site m etastases
78. Are C, Talam ini MA. Lap aroscop y and m alignancy. J Laparoendosc Adv and recurrence after lap aroscop ic colectom y. A rand om ized trial. Surg
Surg Tech A 2005;15(1):38–47. Endosc 1998;12(8):1039–1042.
79. Paolucci V, Schaeff B, Schneid er M, et al. Tum or seed ing follow ing 89. Pearlstone DB, Feig BW, Mansfield PF. Port site recurrences after
laparoscopy: international su rvey. World J Surg 1999;23(10):989–995; laparoscopy for malignant d isease. Semin Surg Oncol 1999;16(4):307–312.
d iscussion 96–97. 90. Abu -Ru stum N R, Rhee EH , Chi DS, et al. Su bcu taneou s tu m or im p lan-
80. Cu ret MJ. Port site m etastases. Am J Surg 2004;187(6):705–712. tation after lap aroscopic proced ures in w om en w ith m alignant d isease.
81. Tseng LN , Berend s FJ, Wittich P, et al. Port-site m etastases. Im p act of Obstet Gynecol 2004;103(3):480–487.
local tissu e traum a and gas leakage. Surg Endosc 1998;12(12):1377–1380. 91. Sem aan AY, Abd allah RT, Mackou l PJ. The role of lap aroscop y in the
82. Iw anaka T, Arya G, Ziegler MM. Mechanism and p revention of p ort- treatm ent of early ovarian carcinom a. Eur J Obstet Gynecol Reprod Biol
site tu m or recurrence after lap aroscop y in a m u rine m od el. J Pediatr 2008;139(2):121–126.
Surg1998;33(3):457–461. 92. Lund berg O. Port site m etastases after lap aroscop ic cholecystectom y.
83. Whelan RL, Sellers GJ, Allend orf JD, et al. Trocar site recu rrence is Eur J Surg Suppl 2000;(585):27–30.
u nlikely to resu lt from aerosolization of tu m or cells. Dis Colon Rectum 93. Matthew s JB. Planned laparoscop ic ap p roach for early-stage gallblad -
1996;39(10 Su p pl):S7–S13. d er cancer: the glass is one-third fu ll. Arch Surg 2010;145(2):133.
PART
VI
Complications of Endocrine
and Oncologic Surgery
CHAPTER
41
Complications of Adrenal Surgery

Paul G. Gauger
■ INTRODUCTION ■ EXPECTED OUTCOMES

Su rgically rem ed iable ad renal d iseases d efine a fascinating For most benign conditions, the disease-related outcomes
sp ectru m from sm all tu m ors w ith large p hysiologic conse- may be relatively independent of the specific surgical
qu ences to physiologically silent large tum ors w ith m ajor approach. This is not true for primary adrenal malignancies
surgical consequ ences. Ad renalectom y is an exam p le of a w here the surgical approach for locally aggressive tumors
proced u re that has been transform ed from an invasive and can more d irectly affect outcomes. Complications and other
tem p orarily d isabling op eration to one that gives m any outcomes important to the patient may be associated with
patients a m inim ally invasive and less m orbid alternative. the particular surgical approach. For example, the open
Yet d iverse com p lications can still ensu e. Som e com p lica- transabdominal approaches may be complicated by pancre-
tions relate to the d isease p rocess being treated and som e atitis, incidental splenectomy, pneumonia, longer hospitaliza-
relate to the sp ecific surgical ap proach. With prop er vigi- tion, and more prolonged recovery. Laparoscopic approaches
lance and p rep aration, m ost com p lications can be either have been shown to be superior to open approaches in terms
avoid ed or m anaged . of length of stay and pain control as well as complication rates
(1,2). Many long-term outcomes are determined by the spe-
cific adrenal disorder being treated.
■ THERAPEUTIC GOALS OF ADRENALECTOMY
Ap p rop riate u tilization of ad renalectom y concep tu ally
ap p lies to (a) p atien ts w ith clin ically or biochem ically ■ Primary hyperaldosteronism
ap p aren t horm on al h yp erfu nction , (b) p atien ts w ith a This chapter w ill d iscuss only su rgically rem ed iable hyp er-
p robable or certain m alignan t ad ren al m ass, and (c) ald osteronism , w hich affects ap p roxim ately tw o-third s of
p atien ts w ith an ad ren al m ass of u ncertain significan ce. all p atients w ith p rim ary hyp erald osteronism . The charac-
Patients w ith horm onal synd rom es for w hom ad renalec- terization of p rim ary hyp erald osteronism , as caused by an
tom y is a consid eration com m only inclu d e those w ith ad renocortical ad enom a, is com monly attribu ted to Jerom e
p rim ary hyp erald osteronism , prim ary or second ary hyp er- Conn (3). Aw areness of p rimary hyp erald osteronism has
cortisolism, and p heochrom ocytom a. For horm onal excess, increased over tim e—and p erhap s along w ith an increase
the goal of ad renalectomy—w hether unilateral or bilateral— in incid ental ad renal im aging. Becau se of variability in
is to p rovid e long-term relief of the horm onal synd rom e. screening p ractices and d iagnostic criteria, Conn synd rom e
Resection of an ad renocortical carcinom a (ACC) is offered is likely m ore com m on than p revalence statistics w ou ld
in the hop e (rarely realized ) of p rovid ing long-term d issu ggest. There is large variability betw een series, bu t per-
ease-free su rvival. Resection of a m etastasis from another hap s 5% to 7% of p atients evalu ated in hyp ertension clinics
m alignancy to the ad renal gland is occasionally ind icated have p rim ary hyp erald osteronism . Althou gh most p atients
if histologic p roof is requ ired to d eterm ine the typ e and (69%) have hyp okalem ia accom p anying hyp ertension, the
intensity of ad ju vant therap y for the p rim ary cancer, or if d iagnosis is often m ore su btle and conventional d iagnostic
the ad renal m ass is the only id entifiable resid u al tu m or in criteria have been exp and ed .
a p atient for w hom rem oval w ou ld be exp ected to be of Primary hyperaldosteronism most often affects patients
benefit. Finally, ad renalectom y m ay be offered to p atients between 30 and 60 years of age (mean 47 years) and is more
for w hom w orku p of an incid entally noted ad renal m ass common in women by a ratio of 2:1 (4). The severity and
has failed to yield a conclu sive etiology and in w hom the d uration of hypertension are often indistinguishable from
risk of observation is d eterm ined to exceed the risk of essential hypertension. Polyuria and nocturia are common.
rem oval. Symptoms of hypokalemia such as muscle w eakness or
cramps may be present. Rarely, period ic paralysis can occur
Paul G. Gauger: University of Michigan Departm ent of as hypokalemia acutely worsens following increased sodium
Surgery, Division of End ocrine Su rgery. intake or administration of potassium-wasting diuretics.
535
536 Part VI • Complications of Endocrine and Oncologic Surgery
Evalu ation of m etabolic an d horm onal d istu rbances is

m ost accu rate if the p atient has a d iet w ith n orm al
sod iu m intake (6 to 9 g/ d ay) and is not taking d iu retics,
-blocker agents, angiotensin-converting enzyme inhibitors,
or angiotensin II recep tor blockers. In this setting, relative
hyp okalem ia, w ith a p otassiu m of 3.9 m Eq/ L, and a
m etabolic alkalosis, w ith H CO 3 of 32 m Eq/ L, are both
consistent w ith the d iagnosis. Tw enty-fou r-hou r u rinary
ald osterone secretion is often elevated . Plasm a ald osterone
levels are m ore com m only obtained . Isolated plasm a ald os-
terone levels m ay not be rem arkably elevated above the
u p p er end of norm al, bu t p atients w ith p rim ary hyp eral-
d osteronism typ ically have p lasma ald osterone concentra-
tions 15 ng/ d L. H ow ever, in the context of a su p p ressed
plasma renin activity, a ratio of plasma ald osterone/ plasma
renin activity 25 is highly su ggestive of p rim ary hyp eral-
d osteronism , w hile a ratio of 20 is u sed in screening to
increase the ability to d etect p atients w ith m ild p rim ary FIGURE 41.1. Arrows indicate a 2.1-cm left adrenal mass seen on CT scan
hyperald osteronism . The ald osterone/ renin ratio is a non- of a 38-year-old male with primary hyperaldosteronism as determined by
hypertension, hypokalemia, and an aldosterone/PRA ratio of 48.
stand ard ized test w ith little p u blished d ata to su ggest
approp riate d iagnostic threshold s. H ow ever, m ost grou p s
u se cu toffs of 20 to 40 for the ratio (5).
Prim ary hyperald osteronism is generally cau sed by (CT) scan (Fig. 41.1). Magnetic resonance im aging (MRI)
either an ad enom a (Conn synd rome) or bilateral hyperp la- scanning is usually m ore expensive and yield s equ ivalent
sia of the zona glom erulosa of the ad renal gland s. The clas- inform ation.
sification of p rim ary hyp erald osteronism has exp and ed to If a u nilateral m ass is evid ent on cross-sectional im ag-
includ e (a) m u ltip le or bilateral ad enom as, or ad enom as ing, it m ay be nonsecreting in the p resence of a contralat-
arising in hyp erp lastic gland s; (b) fam ilial d exam ethasone- eral m icroald osteronom a or a background of bilateral
su p p ressible hyp erald osteronism ; and (c) u nilateral hyp er- hyp erp lasia. A u nilateral ald osteronom a m ay arise in the
plasia (som ew hat controversial). N ot all these entities are backgrou nd of m icroscop ic hyp erp lasia, and yet the
su rgically rem ed iable. As the sp ecific p athop hysiology p atient w ill be cu red by u nilateral ad renalectom y (6,7).
influences the ind ications for operation and , ultimately, the Bilateral ad renal ad enom atou s changes m ay be relatively
exp ected ou tcom es, it is im portant to id entify the sp ecific hyp ersecreting on one sid e only. These variable possibili-
cond ition responsible for primary hyperald osteronism. ties becom e im portant d u ring the p reoperative w orku p
Clinical featu res m ay be som ew hat help fu l in this and p atient selection.
regard . The d egree of hypertension and hypokalem ia is If CT scan d etects a u nilateral ad renal m ass and the con-
often relatively m ore severe in Conn synd rom e than in tralateral ad renal ap p ears norm al, the p resu m p tion that
id iop athic hyp erald osteronism . In resp onse to an u p right this rep resents u nilateral d isease, cu rable by u nilateral
position for 2 hou rs, p lasm a ald osterone increases in ad renalectomy, is correct 90% of the tim e. If there is bilat-
patients w ith id iopathic hyperald osteronism, bu t d oes not eral enlargem ent, it is necessary to corroborate anatom ic
increase in patients w ith Conn syndrome. Id iopathic hyper- d ata w ith fu nctional inform ation from selective adrenal
ald osteronism is su ggested if plasma ald osterone levels are venous sampling.
red u ced in response to saline load ing or cap topril ad m inis- Som e investigators u tilize selective venou s sam p ling in
tration. Seru m 18-OH -corticosterone levels are often ele- an ind ivid u alized or selective m anner w hile others em ploy
vated in Con n synd rom e, bu t they are n ot elevated in the test routinely for functional confirm ation of anatom ic
id iop athic h yp erald osteronism . inform ation. In a recent series, com p ared to p atient selec-
Differentiation of Conn synd rom e from id iopathic tion based on CT resu lts alone, ad renal vein sam pling
hyperald osteronism is an im perfect process. The d ichoto- changed m anagem ent in 36% of p atients w hen em ployed
m ou s concep t of the u nilateral ad renal m ass am enable to rou tinely (7). Ad renal venou s sam p ling for ald osterone lev-
su rgery versu s the bilateral ad renal enlargem ent am enable els provid es the m ost sp ecific confirm ation of a u nilateral
to m ed ical therapy is oversim p lified and d oes not account or bilateral hyp ersecretory p rocess. Ad renal venous sam -
for the full spectrum of disease. Apart from the suggestive p ling is technically d emand ing, related to the challenge of
clinical factors noted earlier, anatomic and functional imag- catheterizing the right central ad renal vein (Fig. 41.2). In
ing tests are necessary. Cross-sectional imaging performed ad d ition to ald osterone levels, cortisol levels are sam pled
under appropriate specific adrenal protocols is quite sensi- to assu re p rop er catheter p osition. Ad renocorticotropic
tive in determining the presence of an adrenal mass. The horm one (ACTH ) is infu sed to equ alize stress-ind u ced
most practical initial imaging test is a computed tomography flu ctu ations in ad renal ou tp u t. Althou gh ACTH is u sually
Chapter 41 • Complications of Adrenal Surgery 537
Table 4 1 . 2 Cr it er ia for in t er p r et a t ion of

select ive a d r en a l vein sa m p lin g d a t a
Ratio Number
Evidence of Catheter Placement in Adrenal Vein
Pre-ACTH adrenal vein cortisol:IVC cortisol 3
Lateralization
Primary Evidence
Dominant aldosterone/cortisol:nondominant 4, preferably 6
aldosterone/cortisol
Supporting Evidence
Dominant aldosterone:nondominant aldosterone 3
Dominant aldosterone/cortisol:IVC 1.5
Nondominant aldosterone/cortisol:IVC 1
FIGURE 41.2. Bilateral adrenal vein catheterization (with contrast injec- ACTH, adrenocorticotropic hormone; IVC, inferior vena cava.
tion into right central adrenal vein) that was done in the course of selective
adrenal venous sampling in a patient with primary hyperaldosteronism.
thought of as a stim ulatory horm one for glu cocorticoid Unilateral ad renalectom y for p rim ary hyp erald ostero-
secretion, it is typical to also observe a brisk resp onse in nism cau sed by a cortical ad enom a nearly alw ays p ro-
ald osterone secretion in the abnorm al gland (Table 41.1). vid es rap id resolu tion of hyp okalem ia. The resid u al need
Thoughtful patient selection and a thorough preopera- for p otassiu m su p p lem ents is ap p roxim ately 1.5% in su r-
tive w orkup are necessary to ensure excellent outcomes. As gically treated p atients versu s ap p roxim ately 80% in m ed -
a general rule, primary hyperaldosteronism caused by an ically treated p atients (7). The resp onse of hyp ertension
adrenocortical adenoma responds to surgical resection while can be m ore variable, from com p lete resp onse to contin-
id iopathic hyperald osteronism d oes not. H ow ever, some u ed reliance on antihyp ertensive m ed ications. H ow ever,
patients with idiopathic hyperaldosteronism who have it is com m on for m ost p rop erly selected p atients to
asymmetric hypersecretion of excess aldosterone respond d ecrease the nu m ber and d ose of antihyp ertensive m ed -
w ell to surgical resection of the d ominant gland . Selective ications. Definitions of cu re are inconsistent, bu t of
venous sampling can be very helpful in id entifying these p atients su ccessfu lly treated , 65% to 70% m ay becom e
patients. Criteria for interpretation of data are shown in norm otensive w hile m ost of the rem aind er w ill im p rove
Table 41.2. Most patients w ith id iopathic hyperald ostero- w ith som e resid u al d egree of hyp ertension. With the
nism and bilateral hypersecretion are treated w ithout opera- assistance of ad renal vein sam p ling in p atient selection,
tion. Both hypertension and hypokalemia can be controlled ap p roxim ately 70% of p atients w ith p rototyp ical Conn
w ith chronic spironolactone or eplerenone therapy. In the synd rom e are norm otensive p ostop eratively w hile 67% of
spectrum of d isease betw een these tw o entities are cortical p atients w ith u nilaterally d om inant bilateral d isease are
adenomas arising in a background of hyperplasia. Hyper- norm otensive p ostop eratively. In p rop erly selected , su rgi-
plasia can occur as an asymmetric (unilaterally dominant) cally treated p atients, only ap p roxim ately 5% w ill have
disease. If this condition can be determined by preoperative resid u al Stage 2 hyp ertension w hile 25% of m ed ically
w orkup, these patients can be offered unilateral ad renalec- treated p atien ts w ill h ave Stage 2 h yp erten sion. Disease-
tomy w ith the expectation of excellent outcomes (7). related ou tcom es are largely in d ep en d en t of sp ecific
Table 4 1 . 1 Select ive a d r en a l ven ou s sa m p lin g for a ld ost eron e a n d cor t isol levels in d ica t in g
over secr et ion of a ld ost er on e from t h e r igh t a d r en a l gla n d
Aldosterone R/L/IVC (1–16 ng/dL) R/L Aldo Ratio Cortisol R/L/IVC (7–22 g/dL) A/C Ratio R/L/IVC Ratio of A/C R/L
3,860/53/39 72 89/25/22 43/2.1/1.7 20
10-, 20-, and 30-min post-ACTH
17,344/504/46 34 486/390/24 36/1.3/1.9 28
20,018/714/87 28 526/401/22 38/1.8/3.9 21
17,984/540/96 33 569/437/28 31/1.2/3.3 25
ACTH, adrenocorticotropic hormone; A/C Ratio, Aldosterone/Cortisol Ratio; R/L/IVC, Right/Left/Inferior Vena Cava.
op erative ap p roach, su ch as anterior ad renalectom y, p os- sity w ith rou nd ed facies, grad u al obscu ration of the ears in
terior ad renalectom y, or lap aroscop ic ad renalectom y. the frontal p rofile, fu llness of the su p raclavicu lar fat pad s,
and a “bu ffalo hu m p .” Skin fragility and bru ising are com -
m on, as are p u rp le striae on the flanks, abd om en, and
■ Hypercortisolism lim bs. H irsu tism , acne, and facial p lethora, as w ell as
All cond itions resu lting from excess glucocorticoid are com - hyp ertension and d iabetes, m ay occu r.
monly know n as Cushing’s synd rome. (Cushing’s d isease is Diagnosis of Cu shing’s synd rom e requ ires biochem ical
Cushing’s synd rome because of an ACTH -prod ucing pitu - confirmation. An effective w ay to establish that hypercorti-
itary ad enom a.) H yp ercortisolism can be classified as either solism exists is a 24-hou r u rinary free cortisol level. Alter-
corticotropin d epend ent or corticotropin ind epend ent. The natively, a low -d ose d examethasone su p p ression test can
former is responsible for 80% of patients w ith hypercorti- be obtained by ad m inistering 1 m g oral d exam ethasone at
solism. Chronic corticotropin (ACTH ) stimulation results in 11 PM follow ed by seru m cortisol d eterm ination at 8 AM the
ad renocortical hyp erp lasia w ith overprod u ction of cortisol next m orning. Classically, p atients w ithou t hypercorti-
and other ad renal hormones. The pitu itary-d epend ent form solism shou ld have cortisol valu e 5 g/ d L w ith this test.
(Cushing’s d isease) accounts for 70% of corticotropin- H ow ever, abou t 15% of p atients w ith Cu shing’s d isease can
d epend ent hypercortisolism, w hile the ectopic ACTH syn- su p p ress w ith d examethasone. If the goal of screening is to
d rome accounts for 10%, usually from small cell carcinoma enhance sensitivity of the test, increasing the stringency of
of the lung, carcinoid tumor, med ullary thyroid carcinoma, this threshold to 1.8 g/ d L w ill increase sensitivity to
or malignant tumors of the pancreas or thymus. With the 95% (8). H ow ever, the resu ltant clinical benefit of d etection
exception of iatrogenic steroid excess, corticotropin-ind e- of m ild cortisol excess is not yet p roven, and d ata regard ing
pend ent hyp ercortisolism im plies prim ary overprod u ction ou tcom es of early id entification and treatm ent of su bclini-
of cortisol from the ad renal gland (s). This cond ition u su ally cal d isease are not conclu sive.
occu rs as a fu nction of a u nilateral cortical ad enom a, To establish w hether the corticotrop in-d ep end ent or
accounting for 10% of patients w ith hypercortisolism over- corticotrop in-ind ep end ent form is p resent, it is necessary
all, bu t it m ay be caused by prim ary hyperplasia of both to m easu re p lasm a ACTH at basal levels. If ACTH is nor-
ad renal gland s. Prim ary ACC can also present as an ad re- m al or elevated , this im p lies corticotrop in-d epend ent
nal m ass accom panied by hypercortisolism . p athop hysiology. A high-d ose (8 m g) d exam ethasone sup -
An ad renocortical ad enom a is best treated by u nilateral p ression test typ ically reveals that p atients w ith Cu shing’s
ad renalectom y. Cu shing’s synd rom e cau sed by prim ary or d isease su p p ress cortisol p rod u ction, w hile those w ith
second ary ad renal hyp erp lasia can often be m anaged m ed - ectop ic ACTH synd rom e d o not. Selective venou s catheter-
ically, bu t w hen this fails, bilateral ad renalectom y is ind i- ization of bilateral p etrosal venou s sinu ses d u ring corti-
cated . In these situ ations, d elayed referral is com m on and cotrop in-releasing horm one stim u lation can confirm
periop erative m orbid ity w ill increase as the ravages of p itu itary hyp ersecretion of ACTH . Patients w ith ectop ic
hyp ercortisolism p rogress. Althou gh m any patients w ith ACTH secretion u su ally have m arked ly elevated corti-
ectopic ACTH synd rom e have ad vanced m alignancies and , cotropin levels, often 200 pg/ mL. If corticotropin levels are
accord ingly, a p oor p rognosis, operation is often ind icated low or und etectable, the suppression of the hypothalamic–
to rem ove the sou rce of ACTH overprod uction and to sim - p itu itary axis is u su ally cau sed by a cortisol-secreting ad re-
plify m ed ical management. If the source of ectopic ACTH nal tu m or.
synd rom e can be localized and safely resected , this is the Ad renal im aging is useful in the setting of hyp ercorti-
most ap p rop riate treatm ent. Because of the sm all size of solism . Since second ary ad renal stim u lation cau sed by
som e tu m ors, su ch as bronchial tu m ors or carcinoid ACTH excess p red ictably affects both ad renals, im aging is
tu m ors, localization is not alw ays possible. In that case, m ost help fu l in the setting of corticotrop in-ind ep end ent
palliative p harm acologic treatm ent w ith ketoconazole, Cu shing’s synd rom e. CT and MRI scanning of the ad renals
mitotane, or octreotid e is ind icated . If this therapy is not can d ocu m ent u nilateral or bilateral enlargem ent.
effective in controlling hyp ercortisolem ia, bilateral ad rena- The treatm ent of Cu shing’s d isease is usually accom -
lectom y is ind icated . Palliative operation m ay involve p lished by (a) transsp henoid al m icrosu rgery to rem ove
bilateral ad renal resection to treat refractory Cu shing’s syn- p itu itary tu m or; (b) external or interstitial p itu itary irrad ia-
d rom e if the secretion of ACTH cannot be ad equately con- tion; or (c) p harm acologic therap y. Bilateral ad renalectomy
trolled . In general, long-term prognosis of patients w ith for control of hyp ercortisolism is occasionally ind icated : (a)
ectopic ACTH synd rom e is poor. Som e patients (bronchial if transsp henoid al resection is not possible or not su ccess-
carcinoid or m ed ullary thyroid carcinom a) m ay live for fu l; (b) if hyp ercortisolism is rap id ly p rogressive and par-
years w ith resid u al neoplasm w hile others (e.g., w ith p an- ticularly severe; (c) if palliation of ectopic ACTH synd rom e
creatic carcinoid or lung carcinom as) have short su rvival. is required ; or (d ) if the patient has prim ary ad renal hyper-
The clinical p resentation of Cu shing’s synd rom e u su - p lasia. Up to 50% of p atients w ith p itu itary Cu shing’s
ally inclu d es insid ious onset of w eakness, increased d isease u ltim ately requ ire bilateral ad renalectom y (9).
appetite, w eight gain, and oligom enorrhea in fem ales. As Ad renalectom y can often be accom plished by a laparo-
the synd rom e d evelop s, patients d evelop centrip etal obe- scop ic or retrop eritoneoscop ic ap p roach, and an associated
increased qu ality of life has been d ocu m ented (10). H ow -

ever, recovery is often p rolonged and incom plete. Ap p roxi-
mately 30% of p atients rem ain hypertensive, 20% continu e
to have d iabetes, and 20% rem ain obese (11).
Until the last tw o d ecad es, ad renalectom y in p atients
w ith hyp ercortisolism w as associated w ith significant m or-
bid ity (abou t 30%) and m ortality (5% to 10%). In recent
series, the ou tcom es have im proved appreciably to a range
that ap p roaches that of treatm ent of other ad renal d iseases.
Ap p roxim ately 10% of patients w ill have a com p lication
such as hem orrhage, d eep venous throm bosis, pu lm onary
em bolu s, resp iratory failu re, coagulopathy, pneu m onia, or
w ou nd infection. Com plication rates are low est in p atients
requ iring u nilateral ad renalectom y (ap proxim ately 10%
morbid ity and 1% m ortality) and are im proved by m ini-
mally invasive approaches. In general, patients requ iring
unilateral ad renalectom y for a hyp ersecreting cortical ad e-
noma have better long-term ou tcom es than those requ iring
bilateral ad renalectom y for m ed ically refractory d isease. FIGURE 41.3. CT scan of a 71-year-old woman with intermittent hypertension,
Patients u nd ergoing u nilateral ad renalectom y have grad - pounding chest sensations, headaches, and elevation of plasma metanephrine
levels. The arrows indicate a 3.8-cm right adrenal pheochromocytoma.
ual d isap p earance of the signs and sym ptom s of hyp ercor-
tisolism and have excellent long-term survival. Althou gh
the m etabolic d erangem ents tend to im p rove in the m onths w ith acceptable sensitivity and specificity. Plasma fraction-
follow ing op eration, it m ay take u p to 12 m onths for som e ated metanephrines involve an assay w ith very high sensi-
of the p hysical changes, su ch as hirsutism , obesity, and tivity (u p to 99%) bu t limited sp ecificity (90%). For that
acne, to reverse. reason, the test perform s best in p atients w ith a higher
pretest probability of pheochromocytoma (e.g., familial
patients). If plasma metanephrines are u sed for rou tine
■ Pheochromocytoma screening d ue to logistical convenience, one must be aw are
Pheochromocytoma is a tu mor d erived from the ad renal of the potential for false-p ositive tests and the need to fol-
med u lla. This tumor ’s physiologic effects d emand accurate low u p w ith a less sensitive (75%), bu t more sp ecific (95%),
and early preoperative d iagnosis to benefit the patient. test (95%) su ch as 24-hou r urinary metanephrine measure-
Although pheochromocytoma is present in only 0.1% to 1% of ments, if clinical uncertainty remains.
hypertensive patients, the overall incidence is approximately When biochem ical testing su p p orts the d iagnosis of
1 to 2 per 100,000. Despite improved clinical understanding pheochromocytoma, evid ence of an adrenal tumor is sought,
of the syndrome, many patients still go und iagnosed . For typ ically, by abd om inal CT or MRI scanning (Fig. 41.3).
patients w ith pheochromocytoma d iscovered at au topsy, Since 10% of p heochrom ocytom as are extra-ad renal, ad d i-
most have d ied sud d enly from myocard ial infarction or tional anatom ic and fu nctional im aging m ay be requ ired .
123
cerebrovascular accid ent, and pheochromocytoma remains I or 131I m etaiod obenzylgu anid ine (MIBG) is a rad ionu -
a cau se of su d d en d eath. clid e that concentrates in abnormal ad renergic tissue. MIBG
The clinical presentation of pheochromocytoma includ es can be very useful in d efining the presence of metastatic or
a w ide array of symptoms. The most typical are headache, extraad renal d isease. In the patient w ith clear-cut clinical
sw eating, palpitations, and episod ic hypertension. Less and biochemical evid ence of pheochromocytoma and a
common symptoms includ e nausea, anxiety, abd ominal u nilateral ad renal mass on CT scan, MIBG scanning ad d s
pain, pallor, and exacerbation of hyperglycemia. Hyperten- little ad d itional p reop erative information (Fig. 41.4) (12,13).
sion is sustained in approximately 50%. The presentation H ow ever, MIBG scanning may still ad d critical information
can occasionally be acute and severe, involving massive cat- for the management of patients w ith bilateral, extra-ad re-
echolamine release from tumor hemorrhage or necrosis and nal, familial, or malignant d isease.
leading to critical hypertension and subsequent cardiovas- Although the first resection of a pheochromocytoma w as
cular collapse. Pheochromocytoma must alw ays be consid - performed in 1926, ad renalectomy remained an operation
ered in the gravid patient w ith a hypertensive crisis during that w as associated w ith high rates of morbidity and mortal-
pregnancy or labor. ity until the introd uction of phentolamine for -receptor
The diagnosis requires d iscriminating clinical suspicion blockad e and norepinephrine for postresection hypotension.
and biochemical confirmation. Serum or urine catecholamine Outcomes have improved substantially in the last decades.
levels are often inaccurate and d ifficult to interpret. Metabo- In large part, complications are related to the hemodynamic
lites of catecholam ines (m etanep hrines, norm etanep hrines, pathophysiology associated w ith the tumor and its removal.
and vanillylmandelic acid) can be measured in the u rine The specific surgical approach does not seem to influence
Right Left
FIGURE 41.4. 123

I metaiodobenzylguanidine scan of the same patient as in Figure 41.5. Concentration of the radionuclide in the right
adrenal (arrow) confirms that the known mass is a pheochromocytoma.
outcomes in any important w ay. Although there w as initial population. Median age at diagnosis is 55 years, and ACC is
concern about the suitability of the laparoscopic approach, more com mon in w omen (60%) than men (40%). Over 20
due to concerns about the pressure of insufflation, manipu- years in the N ational Cancer Data Base, approximately 22%
lation pressure on the tumor, and incomplete resection, the of patients had d istant metastases at the time of d iagnosis
approach is generally as safe as standard open operation and 5-year survival of surgically treated patients was 39%
(14–16). Because of the looser correlation betw een tumor size (20). More than 50% of patients have evid ence of associated
and malignancy compared to cortical tumors, relatively hormonal overprod uction (typically cortisol, occasionally
larger pheochromocytomas may be removed via a laparo- androgens/ estrogens, or aldosterone) at d iagnosis, but
scopic approach (17,18). tumors may be hormonally silent as w ell.
Previou sly, ap p roxim ately 10% of pheochrom ocytom as Com p lete su rgical resection is the only p otentially cu r-
w ere thou ght to be fam ilial in nature. Recent d ata now su g- ative therapy. Adjuvant systemic chemotherapy, adrenolytic
gest that ap p roxim ately 25% of unselected patients w ith agents, and extern al beam rad iotherap y h ave n ot m et
pheochrom ocytom a have d em onstrable germ line d efects. w ith pred ictable success. Completeness of resection is the
These are typ ically von H ipp el–Lind au d isease, m u ltip le strongest pred ictor of outcome in this d isease. The 5-year
end ocrine neop lasia type 2, and succinate d ehyd rogenase actuarial survival following potentially curative resection
su btyp e D and B m u tations (associated w ith p heochrom o- ranges from 32% to 48% (21). If curative resection requires
cytom a/ p aragangliom a synd rom e) (19). Overall, the risk removal of tumor thrombus in the renal vein or inferior vena
of recu rrence is consid ered to be approxim ately 10%. This cava or extend ed local resection, this circumstance d oes not
nu m ber is not based on specific d ata, and long-term ou t- by itself predict a dismal prognosis unless gross resid ual
com es after resection for pheochrom ocytoma are influ- tumor remains. If patients und ergo incomplete initial resec-
enced by factors such as fam ilial d isease and clinical tion, p rognosis is u niform ly p oor w ith m ed ian su rvival
evid ence of m alignancy. 1 year (21). Risk of death increases w ith ad vanced age,
poorly differentiated tumors, margin-positive resections,
and nodal or distant metastases (20).
■ Adrenocortical carcinoma The im p act of system ic chem otherap y and agents su ch
Although accounting for a tiny fraction of human malignan- as m itotane u p on su rvival is very d ifficu lt to ascertain.
cies, ad renal cancer remains one of the most malignant of Although m any regim ens have prod u ced rare com plete
endocrine tumors. Annual incid ence is about 2 per million resp onses and occasional p artial resp onses, it is d ifficult to
translate these retrosp ective d ata into coherent clinical Table 4 1 . 3 Et iology of a d r en a l in cid en t a lom a s
practice and d evelopm ent of stand ard ized ad ju vant regi-
mens has been slow. Tw o com m on regim ens are as follow s: Percentage of
Lesion Incidentalomas
(1) etop osid e, d oxorubicin, cisplatin (w ith or w ithou t
mitotane) and (2) strep tozotocin w ith m itotane. Mitotane is Nonfunctioning cortical lesions 80
an ad renolytic d ru g that m ay prolong recurrence-free su r- Subclinical Cushing’s syndrome 5
vival in p atients w ith com pletely resected ACC (22), Pheochromocytoma 5
althou gh the im p ortance of com plete resection cannot be
Aldosteronoma 1
overem p h asized . Rad ioth erap y (typ ically 40 Gy frac-
tionated over 5 to 6 w eeks) m ay be consid ered for the Adrenocortical carcinoma 5
ad renal bed in patients w ith incomplete resection, ad vanced Metastasis 2.5
locoregional d isease (e.g., Stage III), or apparently high- Ganglioneuroma, myelolipoma, cyst, etc. 2
grad e and aggressive prim ary tum ors. Postoperative rad io-
therap y is associated w ith a low er risk of local failu re than Adapted from Zeiger MA, Thompson GB, Duh QY, et al. AACE and AAES medical
lack of rad iotherapy (23). Targeted m olecular therap ies guidelines for the management of adrenal incidentalomas. Endocr Pract 2009;
(e.g., inhibitors of IGF-1R/ IR) are in d evelopm ent or in 15:1–20.
trial.
Ap p roxim ately 64% of patients d evelop local recu r-
rence or d istant m etastases after attem p ted curative resec- hyp erfu nction; (b) w hether it has characteristics of an ad re-
tion (24). Ap p roxim ately 40% of patients w ith recu rrence nal m alignancy; and (c) w hether the p atient has a history of
are am enable to reoperation and have a 5-year su rvival of p reviou s m alignancy, w hich cou ld be related . All p atients
50%. Patients w ho d o not und ergo resection have a 5-year shou ld u nd ergo biochem ical testing to exclu d e hyp eral-
su rvival of 8% (25). Ou tcom es for ACC m ay be related to d osteronism , hyp ercortisolism , and p heochrom ocytom a.
the sp ecific su rgical app roach. ACC is a m axim ally aggres- For p atients w ith hyp ertension, a p lasm a ald osterone con-
sive tu m or and m in im ally invasive tech niqu es are not centration and p lasma renin activity are obtained to calcu -
app rop riate. One series retrospectively com pared p atients late the ald osterone/ renin ratio. Plasm a-free m etanephrine
treated by op en ad renalectom y and lap aroscop ic ad rena- levels or 24-hou r u rinary fractionated m etanephrine levels
lectom y and found a significantly elevated risk of tu m or are ap p rop riate to ru le ou t p heochrom ocytom a. Either a 24-
ru ptu re and p ositive m argins (50% vs. 18%) w ith lap aro- hou r u rinary free cortisol m easu rem ent or a low -d ose d ex-
scop ic ap p roaches (24). This w as likely related to the am ethasone su p p ression test is necessary to exclu d e
shorter m ean tim e to local recu rrence (9.6 m onths vs. hyp ercortisolism . The sp ecific characteristics of cross-sec-
19.2 m onths) for lap aroscop ic ap p roaches. This risk of tional im aging help to clarify the possibility of m alignancy.
recurrence w as greater even w hen sm aller ACCs w ere The u nenhanced tu m or d ensity and the p ostcontrast
rem oved by lap aroscopic approaches (24). Althou gh tu m or w ashou t d ensity are very u sefu l in d etermining w hich
biology likely p lays a significant role, argum ents for tum ors are likely to be lipid -rich ad enom as and w hich are
laparoscopic rem oval of know n or likely ACCs are flaw ed . likely to be “som ething else”— often a tu m or that w ill u lti-
This issu e is a good exam p le of how p rop er p atient and m ately requ ire su rgical therap y. Concerning features
proced u re selection can be related to d isease-sp ecific inclu d e ind istinct bord ers and u nclear relation to su r-
patient ou tcom es and com plications. rou nd ing organs and tissu e p lanes, u nenhanced d ensity
10 H ou nsfield Units, 15-m inu te d elayed enhancem ent
w ashou t of 60%, and absence of signal intensity loss on
■ Adrenal incidentaloma ou t-of-p hase MRI sequ ences. To p revent inap propriate
An “incid entalom a” is a m ass of the ad renal gland d iscov- p atient and p roced u re selection, su rgeons mu st be vigilant
ered serend ip itously, w hich is u nrelated to the p atient’s and objective d u ring this p rocess to avoid offering patients
clinical p resentation. With the increase in high-resolu tion, w ith a p ossible ACC a lap aroscop ic resection.
cross-sectional im aging of the abd om en, it has becom e The workup of an incid entaloma is aimed at segregating
app arent that these tum ors are relatively com m on—u p to lesions into those that should be treated with resection (e.g.,
4% of p atients u nd ergoing abd om inal cross-sectional im ag- cortical adenoma causing Conn’s syndrome or Cushing’s syn-
ing (26,27). Staging CT scans for patients w ith a know n drome, pheochromocytoma, and ACC) or observation (e.g.,
malignancy are not inclu d ed in the d efinition of ad renal small benign nonfunctional cortical adenoma and myelolipo-
incid entalom a. Most (80%) are nonfunctioning cortical ad e- mas). Despite these efforts, many patients fall outside these
nomas and are thu s nonthreatening (see Table 41.3). H ow - categories and have an incidentaloma of uncertain signifi-
ever, abou t 10% of ACCs are initially d iscovered as cance that requires resection. An example of this dilemma is a
incid ental ad renal m asses, highlighting the need for ap p ro- patient without evidence of hormonal hyperfunction but
priate w orku p (Fig. 41.5). Whenever a m ass is d iscovered , w ith a large ad renal mass ( 4 cm) that may or may not have
it is com pulsory to com plete basic investigations to d eter- atypical imaging characteristics, such as an increased density
mine (a) w hether the m ass is associated w ith horm onal per CT scan or delayed contrast washout.
A B
FIGURE 41.5. These paired images indicate the necessity of an appropriate workup of the incidental adrenal mass (arrows). Initially,
this 64-year-old woman had the CT scan (A) performed after a motor vehicle accident. The left adrenal abnormality was ascribed to
trauma and no further workup done. Five years later, another CT scan (B) revealed a 13-cm left adrenal mass typical for adrenocortical
carcinoma as well as small liver metastases.
Avoid ing need le biop sy of an ad renal m ass m ay p re- previous deep venous thrombosis, should have periopera-
vent p otential com p lications d u ring w orku p. With the tive prophylaxis in alignm ent w ith current clinical guid e-
excep tion of a p atient w ith a prim ary m alignancy, su ch as lines. Deep venou s throm bosis p rop hylaxis is ap propriate
lung, renal cell, breast, or m elanom a, w hereby a second ary for abd om inal lap aroscopic proced ures as w ell.
ad renal metastasis is possible, there is no real role for nee-
d le biop sy. The test is not sensitive enou gh for reliable d is- ■ Hyperaldosteronism
crimination of benign and m alignant tissue. N eed le biop sy
can be critically d angerou s if the tu m or is a p heochrom ocy- Once the d iagnosis of prim ary hyperald osteronism has
toma. If the tu mor is an ACC, the capsule w ill be broken, been m ad e, it is help fu l to start the p atient on sp ironolac-
w hich can m itigate the cu rative p otential of su bsequ ent tone therap y (typ ical d ose of 50 to 100 m g PO b.i.d .) at least
resection. 2 w eeks before op eration. Therap y is u su ally effective in
controlling blood p ressu re p reop eratively and blu nts m in-
eralocorticoid -related electrolyte changes arou nd the tim e
■ IDENTIFICATION AND MODIFICATION of op eration. If a p atient is also receiving p otassium su p-
OF PREOPERATIVE RISK FACTORS p lem entation, it is im p ortant to check the seru m p otassium
■ General risks level a few d ays after starting Ald actone as p otassiu m
requ irem ents m ay d ecrease su bstantially.
As w ith any major surgical procedure, the patient needs to
be assessed for pulmonary and card iac comorbidities as w ell
as risk for deep venous thrombosis and related pulmonary
■ Hypercortisolism
embolism. Patients w ith significant limitation of pulmonary There is a generally accep ted , bu t p oorly d ocu m ented ,
function may be guid ed tow ard a laparoscopic approach if it observation that tissu e integrity is lessen ed in Cu sh ing’s
is clinically appropriate, since postoperative pain and respi- synd rom e so that intraop erative blood loss is increased .
ratory impact w ill be less than w ith an open approach. Man y p atien ts w ith h yp ercortisolism h ave d iabetes or
Patients w ith significant CO 2 retention need close monitor- glu cose in tolerance. Periop erative attention to th is factor
ing d uring the insufflation associated w ith laparoscopy— is requ ired to p rovid e tight glu cose control. The m ain
especially d uring prolonged proced ures. With the exception sp ecific risk of ad renalectom y for hyp ercortisolism is
of pheochromocytoma or significant intraoperative bleed- p ostop erative hyp oad renalism d u e to su p p ression of the
ing, the physiologic challenge of ad renalectomy is mod erate. h yp othalam ic–p itu itary–ad renal axis. For this reason,
However, it is prudent to institute perioperative -adrenergic p reop erative stress d ose steroid s are given (100 m g
blockade in patients with significant coronary artery disease. h yd rocortisone IV im m ed iately p reop ). Ongoing p ostop -
Patients with risk factors for postoperative deep venous erative corticosteroid rep lacem en t shou ld be an ticip ated
thrombosis, such as obesity, age 40 years, malignancy, and for m any m onths.
■ Pheochromocytoma venou s 3 d im ensional reconstru ction, contrast venography,

or intravascu lar u ltrasou nd . If involvement is extensive,
Preop erative p harm acologic preparation is m and atory to the patient m u st be prepared for potential thoracoabd om i-
d ecrease hem od ynam ic com plications. The m inim u m nal access or venovenou s byp ass to facilitate com p lete vas-
period for p rep aration likely is 7 to 10 d ays preop eratively. cu lar control for caval resection and reconstru ction.
The m ost com m on m ethod is to establish -ad renergic For left-sid ed tu m ors, the consid erations abou t possible
blockad e w ith p henoxybenzam ine and later -ad renergic nep hrectom y are id entical. The p atient shou ld be coun-
blockad e if necessary. Phenoxybenzam ine shou ld be seled on p otential d istal p ancreatectom y or p artial colec-
started at a d ose of 10 m g PO b.i.d . or t.i.d . and titrated tom y if the colonic m esentery is involved . If a sp lenectom y
up w ard u ntil m ild orthostatic sym ptom s occu r. Frequ ent is p otentially requ ired , p neu m ococcal, m eningococcal, and
blood p ressu re and pu lse checks should be rep orted in Haemophilus influenza B vaccinations shou ld be p rovid ed at
ord er to m anage d osage increases. A few p atients are sensi- least 2 w eeks before op eration.
tive to the d ru g and m ay be w ell prep ared on as little as 30
to 40 m g/ d ay, bu t som e p atients w ith very active tu m ors
can requ ire as m u ch as 150 m g/ d ay or m ore. If the p atient ■ Critical principles of patient selection
is on the m axim u m tolerated d ose of phenoxybenzam ine Im p ru d ent p atient selection increases com p lication rates. A
and reflex tachycard ia is present, prop ranolol shou ld be nu m ber of gu id ing p rincip les offer the ap p rop riate balance
started at 10 m g PO t.i.d . Chronically contracted intravas- betw een short-term and long-term ou tcom es. In general,
cu lar volu me is restored by ad equate flu id and salt intake p atients w ith a benign fu nctioning ad renal tu m or, such as
d u ring -ad renergic blockad e. Alternative regim ens based cortical ad enom a or p heochrom ocytom a, shou ld be offered
on short-acting 1-antagonists (e.g., prazosin or d oxazosin) lap aroscopic ad renalectom y unless specific contraind ica-
or calciu m channel blockad e (e.g., nicard ipine) can also be tions exist—for exam p le, p rohibitively extensive previous
effective and are often better tolerated than phenoxybenza- su rgery. This is a relative and ind ivid u alized issue since
m ine. Few com p arative d ata exist. An arterial line shou ld lap aroscopic ad renalectom y m ay still be accom p lished by
be p laced before op eration becau se w ith intraop erative experienced surgeons follow ing previou s abd om inal pro-
m anip u lation rapid and severe hem od ynam ic changes ced u res. Posterior retrop eritoneoscop ic ap p roaches to the
m ay occu r. Intraoperative m agnesiu m infu sion can con- ad renal have been d evelop ed as an alternative to stand ard
tribu te to hem od ynam ic stability by inhibiting release of transperitoneal laparoscop ic approaches and are m eeting
catecholam ines from the ad renal m ed u lla and p erip heral w ith excellent ou tcom es. The p osterior op en app roach m ay
ad renergic nerves as w ell as by a d irect vasod ilating action rarely be u sefu l in p atients w ho are excep tionally obese
on vessel w alls. w here lap aroscop ic access is d ifficu lt or d angerous. If the
tu m or is an ACC, the p atient shou ld be offered open ante-
rior ad renalectomy in all instances. If the tu m or is excep-
■ Adrenocortical carcinoma tionally large and d ifficulty w ith exp osu re and vascu lar
The m ost im p ortant risks are related to hyp erfu nction and control is anticip ated , a thoracoabd om inal approach m ay
to the tu m or ’s anatom ic extent. If hypercortisolism exists, best suit the situation.
the p atient w ill need p eriop erative stress d ose steroid s and Desp ite these gu id elines, u nclassified p atients w ith
ongoing p ostop erative su p p lem entation becau se of su p - “incid entalom as” of u ncertain significance are not easily
pression of the hyp othalam ic–pitu itary–ad renal axis. H ow - categorized as to op erative ap p roach. These patients usu -
ever, if a cortisol-prod u cing ACC is incom pletely resected ally requ ire ad renalectom y d u e to the concern that the
or recu rrent, ind ivid u al patients m ay actu ally requ ire m ass “cou ld ” be cancer. Since ACCs shou ld not be resected
ad renolytic m ed ications to control the d egree of hyp ercor- lap aroscop ically, the qu and ary is w hether all p atients w ith
tisolism . Althou gh many ad renocortical cancers are region- ind eterm inate incid entalom as require open ad renalectom y.
ally extensive or have intra-abd om inal m etastatic d isease, Thou ghtfu l and honest p atient and p roced u re selection is
aggressive resections are often appropriate. A safe op era- key. Althou gh there is no role for lap aroscop ic rem oval of
tion to p rovid e for gross total rem oval w ithou t cap su lar a know n or likely ACC (24,28), lap aroscop ic resection is
breach is the goal. ap p rop riate for rem oval of ind eterm inate incid entalom as
For right-sid ed cancers, one m ust assess w hether lim - that cou ld conceivably be sm all ACCs—inapparent u ntil
ited hepatic resection w ill be required for gross tum or final histology. The rationale for this conu nd ru m is that the
rem oval and w hether the tu m or invad es the su p erior p ole benefits of lap aroscopic ad renalectom y are clear and w ill
of the kid ney or the renal hilum , ind icating the need for en be provid ed to many patients w hile the negative influence
bloc nep hrectomy. N ative renal fu nction m ust be consid - of inad vertent lap aroscop ic removal of ACC is not yet fu lly
ered to d eterm ine that this is safe. If there is obliteration of ap p reciated and w ill p otentially affect far few er p atients.
the p lane betw een the tu m or and the inferior vena cava, the Criteria that gu id e p atient selection inclu d e (a) tu m or
possibility of caval invasion or intracaval tum or throm bu s size, (b) tu mor fu nction, and (c) im aging characteristics.
extension mu st be consid ered . The extent of caval tu m or With few excep tions, lesions 6 cm in d iam eter should be
shou ld be investigated p reop eratively w ith MRI w ith rem oved by op en anterior ap p roach. These exceptions m ay
be proven p heochrom ocytom as w ith no preop erative evi- rem oval of sm all incid ental ad renal tu m ors. Coincid ent
d ence of m alignancy or occasional large benign tum ors w ith the rise of incid ental ad renal imaging and laparoscopic
such as myelolip om as or cysts. Lesions 4 cm w ithou t evi- ad renalectomy, the overall u tilization of ad renalectomy has
d ence of hyperfu nction m ay be observed longitu d inally risen 43% betw een 1988 and 2000 (31). Most of this increase
w ith removal reserved for d em onstrated grow th or change has been to treat benign ad renal neoplasm s and ad renal
in fu nction (29). Observation inclu d es not only reim aging, neoplasm s of uncertain behavior.
bu t reassessm ent of fu nctional im plications (27). Lesions
betw een 4 and 6 cm shou ld be com pletely resected by
laparoscopic ap proach if (a) there are no contraind ications
■ Open anterior adrenalectomy
to laparoscop y, (b) there are no su spiciou s fu nctional char- An ad renal m ass that is p otentially an ACC shou ld be
acteristics, or (c) there are no su spiciou s im aging character- resected by an op en ap p roach. Typ ically, this is accom -
istics. Su sp iciou s fu nctional characteristics inclu d e excess p lished via a bilateral su bcostal or m id line incision (Fig.
secretion of and rogens or cortisol, m ixed excess secretion 41.6). Occasionally, very large tu m ors m ay requ ire thora-
of ald osterone and cortisol, and excess secretion of estrogen coabd om inal access, esp ecially if extensive en bloc resec-
secretion in a male. Susp icious cross-sectional im aging tion w ith control of the inferior vena cava is requ ired (Fig.
characteristics have been d iscu ssed earlier. 41.7). Vascu lar control m ay be requ ired for the inferior
The benefits of laparoscopic ad renalectomy compared to vena cava, renal vessels, and aorta. Exp osu re m u st be ad e-
open ad renalectomy have been show n in multiple series. qu ate to allow en bloc resection of involved contigu ou s
When ad ju stment occu rs for confou nd ing variables, the stru ctu res, su ch as kid ney, liver, sp leen, and p ancreas. It is
operative times, transfusion requirements, reoperations, critical to avoid cap su lar breach and tu m or sp ill. If the
length of stay, and 30-d ay m orbid ity rates are all greater for tu m or is a large p heochrom ocytom a, the ad age of “d issect-
open ad renalectomy (30). An issue related to patient and ing the p atient aw ay from the tu m or” shou ld be heed ed to
proced ure selection is the potential for availability of a low avoid rou gh p hysical m anip u lation of the tu m or, w hich
morbid ity operation such as laparoscopic ad renalectomy to can p rovoke hyp ertension and intraop erative hem od y-
lead to treatm ent bias and a low ering of the threshold for nam ic lability.
'04
HRF
A B C
FIGURE 41.6. Standard incision placement for various open approaches to the adrenal gland—A: anterior; B: posterior;
C: thoracoabdominal.
often large venou s collaterals that requ ire ligation. The

tu m or ’s inferior m argin is sep arated from the kid ney’s
su p erior p ole. If there is evid ence of transcap su lar invasion
of the renal p arenchym a, the inferior m argin of the resec-
tion is changed to m obilize the kid ney en bloc, and the
renal hilar vessels are d efined .
If the opportu nity arises to expose and d ivid e the cen-
tral ad renal vein early in the d issection, this vein should be
controlled and transected . This is not often the case w ith
large m alignant m asses, and in that circu m stance, the
tu m or shou ld be m obilized u ntil the central ad renal vein is
the last m ajor p oint of attachm ent. If there is transm u ral
venou s invasion or significant caval throm bu s, partial
caval resection m ay be requ ired . If the resulting caval
d efect is ellip tical, a p atch of bovine p ericard iu m or polyte-
traflu oroethylene (PTFE) m ay be u sed . If the d efect is cir-
cu m ferential, a ribbed PTFE interp osition graft m ay be
FIGURE 41.7. Magnetic resonance imaging of a 51-year-old woman with a u sed , w ith the assistance of venovenou s byp ass circulation
20-cm nonfunctioning low-grade adrenocortical carcinoma (arrows). The d u ring graft p lacem ent.
vena cava is severely compressed but not directly invaded. Preoperative cross-sectional im aging of large right-
sid ed m alignant m asses often raises the concern of involve-
m ent of the ad jacent hep atic p arenchym a. If hepatic
For right ad renalectom y, m obilization of the hep atic invasion lim its cu rative resection, the d issection can pro-
flexu re of the colon and a p artial Kocher m aneu ver is often ceed u nd er Glisson cap su le or w ith a nonanatom ic hep atic
requ ired . The right hepatic lobe is mobilized by d ivid ing p arenchym al resection.
the triangu lar ligam ent. The lobe m ust be fu lly m obilized For open anterior left ad renalectomy, there are tw o main
to a point that the posterolateral portion of the intrahepatic approaches to expose the ad renal tumor. The first approach
cava is w id ely seen. This exposu re is necessary to d eter- involves opening the gastrocolic omentum and reflecting the
m ine the extent of su prahepatic caval involvem ent—if splenic flexure of the colon caud ad . From w ithin the lesser
present. It is often useful to d ivid e the inferior phrenic vas- sac, the inferior margin of the pancreas is mobilized and ele-
cu lar p ed icle early in the d issection to allow the tu mor to vated to expose the adrenal tumor (Fig. 41.8). This maneuver
be retracted slightly cau d ad as it is sep arated from the is useful if the adrenal gland is located posterior to the pan-
d iaphragm . The tum or ’s lateral m argin is m obilized . If creatic tail or slightly caud ad . This approach m ay provid e
there is su bstantial involvem ent of the vena cava, there are inadequate exposure if the adrenal gland is cephalad to the
FIGURE 41.8. Infrapancreatic

approach to the left adrenal gland
after division of the gastrocolic
omentum to open the lesser sac.
Stomach
Divided gastrocolic
ligament
Inferior border
of pancreas
Adrenal tumor
Left kidney
pancreatic tail or in the case of large tumors. In that case, an ad renalectom y. Occasionally, this ap p roach on the left m ay
alternative approach involves d ividing the superior and lat- be accom p lished w ithou t p leu ral entry. After ad renalec-
eral splenic attachments to mobilize the spleen and distal tomy, the d iap hragm and p eritoneu m are rep aired . A tu be
pancreas en bloc via partial medial visceral rotation. It is thoracostom y is necessary if the p leu ral cavity is entered .
often possible to expose and d ivid e the central ad renal vein
early in the dissection w here it joins w ith the left renal vein.
It is helpful to d ivid e the inferior phrenic ped icle early in the
■ Laparoscopic transperitoneal adrenalectomy
dissection as well to allow some caudad retraction of the The patient is secu red w ith a p ad d ed beanbag in flank posi-
tumor. With large tumors, splenectomy may be necessary tion w ith the table flexed . The arm s mu st be p ad d ed and
due to tumor invasion or to provide adequate exposure. An secu red in gentle anterior flexion. Typ ical p ort p lacem ent is
en bloc distal pancreatectomy may also be necessary because along the line of a su bcostal incision w ith the exception of
of local invasion. N ephrectomy may be required for renal the cam era p ort (for a 30-d egree su rgical telescope). It is
parenchymal invasion or hilar vessel involvement. often u sefu l to triangu late that p ort ou t of line w ith the oth-
ers tow ard the u m bilicu s, w hich d ecreases intracorporeal
instru m ent collisions. For right ad renalectom y, an ad d i-
■ Open posterior adrenalectomy tional p ort is u su ally necessary for retraction of the right
A d irect rou te to the retrop eritoneu m can avoid the m or- lobe of the liver after it is m obilized . The right lobe of the
bid ity associated w ith m ajor laparotom y. A hockey liver is m obilized by d ivid ing the triangu lar ligam ent w ith
stick–typ e incision is carried d ow n to the level of the ip si- an u ltrasonic shears. This is d one p rogressively to open the
lateral paraspinou s m u scle and carried obliqu ely over the space anterolateral to the ad renal gland u ntil the vena cava
course of the 12th rib (Fig. 41.6). The latissim us d orsi fibers is seen. After d ivision of Gerota fascia, blu nt d issection
are d ivid ed , and the p araspinous m u scle is m obilized betw een the vena cava and the m ed ial m argin of the gland
med ially bu t not d ivid ed . The 12th rib is resected su bp e- w ill d efine the central ad renal vein. This vein is taken
riosteally, avoid ing the intercostal bu nd le. It is easy to betw een end oscop ic clip s and d ivid ed . If the vein is p artic-
violate the p leu ra here and enter the costophrenic su lcu s— u larly broad , d ivision m ay requ ire ap p lication of an end o-
especially in the m ed ial portion of the field . If pleu ral entry scop ic linear stap ler. The inferior p hrenic p ed icle is d ivid ed
occurs, it is straightforw ard to evacu ate the resu ltant air after controlling sm all vessels w ith end oscop ic clip s or the
from the p leu ra and close this again. A tube thoracostom y u ltrasonic shears. The rem aining attachments includ e sm all
is unnecessary if no pu lm onary inju ry is incu rred . When arterial branches from the renal artery or aorta, w hich can
the retrop eritoneu m is entered , the kid ney is p alpated in be easily controlled w ith the u ltrasonic shears. The gland is
the d eep m ed ial asp ect of the w ou nd and gently p u lled rem oved in an end oscop ic sp ecim en bag.
cau d ad to allow the ad renal m ass to be exp osed . Becau se For left-sid ed lesions, the p ort p lacem ent is sim ilar, and
the right ad renal gland is anatom ically p osterior to the a fou rth p ort is only necessary w hen the sp leen is d ifficult
inferior vena cava, the central ad renal vein is the last m ajor to reflect ad equ ately. After introd u ction of the 30-d egree
stru ctu re seen and d ivid ed w hen rem oving the right ad re- scop e and instru m ents, the lateral attachm ents of the
nal gland by this ap proach. This effect is less p ronou nced sp leen are d ivid ed w ith u ltrasonic shears. To begin this d is-
on the left sid e w here the central ad renal vein m ay be section, it m ay be necessary to take d ow n the sp lenic flex-
encountered and d ivid ed earlier in the d issection. Overall, u re of the colon by d ivid ing the lienocolic ligam ent in a
this ap p roach is rarely u sed and its p lace in the su rgical lim ited fashion. As the p lane is d evelop ed , the sp leen w ill
arm am entariu m has largely been su pplanted by the p oste- begin to fall m ed ially. The p lane m u st be d evelop ed poste-
rior retrop eritoneoscop ic ap p roach. rior to the p ancreatic tail to locate the ad renal gland w ith-
ou t inju ring the p ancreas. This d issection m ust be
continu ed u ntil the ad renal gland is seen, w hich w ill be
■ Open thoracoabdominal adrenalectomy nearly ad jacent to the aorta. Sm all gland s m ay be obscured
Because of the associated pu lm onary m orbid ity of this in retrop eritoneal fat, esp ecially in m ales and in patients
approach, it is u sed only for very large m alignant ad renal w ith Cu shing’s synd rom e. Lap aroscop ic u ltrasound can
masses. Althou gh occasionally necessary on the left sid e, a help id entify the gland and ind icate the prop er target for
thoracoabd om inal incision is m ost relevant to large right- exp osu re. Once the gland is located , it is circu m ferentially
sid ed ACCs w hen venou s involvem ent is p resent. The m obilized w ith u ltrasonic shears. The inferior phrenic
patient is p ositioned interm ed iate betw een supine and p ed icle and the central ad renal vein are exp osed w ith blu nt
flank orientation w ith the table flexed (Fig. 41.6). A single d issection. These stru ctu res are controlled w ith end oscopic
incision is m ad e over the 10th rib (11th on the left) and car- clip s and d ivid ed . On the left, there is often an anastom otic
ried obliqu ely onto the abd om en. The rib is resected su bp e- vein betw een these tw o vessels, and it is im p ortant to
riosteally. The d iap hragm is d ivid ed cu rvilinearly to lim it d ivid e these m ain veins aw ay from the anastam otic com -
d enervation of fibers that are d istribu ted from the central p lex to p revent bleed ing. The central ad renal vein is often
aspect. Su p erior retraction of the lu ng and anterior retrac- short, bu t it is u su ally not necessary to exp ose the left renal
tion of the right hep atic lobe p rovid es w id e exp osu re for vein in ord er to safely d ivid e it.
■ Posterior retroperitoneoscopic adrenalectomy hyd rocortisone every 6 hou rs on the d ay of the op eration.
Usu ally, 200 m g hyd rocortisone d istribu ted over p ostop -
An anatom ically d irect vid eoscop ic ap p roach to the ad re- erative d ay 1 and 100 m g over p ostop erative d ay 2 is ad e-
nal, w hich m inim ized d issection and afford ed early qu ate. When oral alim entation is established , the d ose is
access to the central ad renal vein, has been p op u larized converted and w eaned to a m aintenance d ose of ap p roxi-
by Walz et al. (32). After initial d escrip tion as a three-p ort m ately 15 to 37.5 m g hyd rocortisone p er d ay, d ivid ed into
techniqu e (33), it has evolved into a single-p ort alterna- three d oses. Follow ing u nilateral ad renalectom y, th e
tive (34). Yet, m any su rgeons have been slow to ad op t this recovery of the h yp op h yseal–p itu itary–ad renal axis can
ap p roach d u e to p erceived concerns of lim ited exp osu re be d eterm ined w ith a Cosyntrop in stim u lation test no
and op erating sp ace, as w ell as lack of trad itional fam iliar earlier th an ap p roxim ately 3 to 6 m onths. H ow ever, it
anatom ic land m arks. As w ith the open posterior ap p roach, shou ld be u nd erstood that average tim e to recovery of
the retrop eritoneoscop ic ap p roach allow s access to the the H PA axis is u su ally 1 year. An alternative strategy
ad renal gland w ithou t traversal of the p eritoneal sp ace m ay ap p ly to p atien ts in w hom th e su p p ression of the
bu t ad d s the p atient benefits of m inim ally invasive tech- h yp op h yseal–p itu itary–ad renal axis is con ceivable, bu t
niqu es. With the p atient in p rone p osition, the ap p roach n ot likely. In this case, a Cosyn trop in stim u lation test
u su ally u ses three or few er trocar sites, and the retrop eri- m ay be p erform ed on th e m orning of p ostop erative d ay
toneal sp ace is created and m aintained by high-p ressu re 1. This is d one by ad m inistering 250 g Cortrosyn IV.
p neu m oretrop eritoneu m (20 to 24 m m H g), w hich is w ell Cortisol m easu rem en ts are obtained at 0, 30, and 60 m in-
tolerated by p atients com p ared to sim ilar d egrees of u tes after ad m inistration. A cortisol level 18 g/ d L
p neu m op eritoneu m . Becau se of the excellent visu aliza- ind icates su fficient fu nction. If the hyp op hyseal–p itu -
tion via this ap p roach, p artial ad renalectom y is also p ossi- itary–ad renal axis is intact, the p atient w ill not need su p -
ble if a cortical-sp aring p roced u re is ind icated (35). This p lem ental steroid s bu t w ill still need to be cou nseled
ap p roach is not ap p rop riate for p rim ary ACC, bu t iso- abou t the critical sym p tom s and signs of ad renal insu ffi-
lated m etastases have been su ccessfu lly rem oved in this ciency.
fashion (36).
■ Hernia
■ IDENTIFICATION AND MANAGEMENT Incisional hernia can be a long-term com plication of any
OF POSTOPERATIVE COMPLICATIONS ap p roach to the ad renal gland . H ernia m u st be d istin-
gu ished from segm ental abd om inal m u scle relaxation d ue
■ Bleeding
to d enervation resu lting from ap proaches such as the pos-
Although usually avoid ed w ith carefu l and patient app li- terior or thoracoabd om inal incisions that requ ire rib resec-
cation of su rgical techniqu e, significant bleed ing can occu r tion. Although incisional hernia m ay be related to operative
w ith any ap p roach to the ad renal gland . H em orrhage is choices and techniques, it also appears to be more likely to
often from inju ry to the renal vein, inferior vena cava, or occur in patients w ith hypercortisolism d ue to poor tissu e
liver on the right or to the renal vein, splenic vein, or sp leen integrity at the time of port site closu re.
on the left. Major bleed ing d u ring right ad renalectom y
may be cau sed by failu re to recognize the right hepatic vein
or an aberrant central ad renal vein that d rains into the right
■ Hypertension
hep atic vein. Often, a hole in the inferior vena cava can be H yp ertension can be an ind ication of incom p lete resection
prim arily rep aired w ith su tu re venorrhaphy, but occasion- of a horm onally active tu m or. Esp ecially w ith hyperald os-
ally a p atch of bovine pericard ium or PTFE may be requ ired teronism , the p atient may also be left w ith u nd erlying
to p revent iatrogenic inferior vena cava stenosis. essential hypertension even after excess ald osterone secre-
tion is ad d ressed . An occasional cau se of p ostop erative
hyp ertension m ay be inad vertent inju ry to a renal artery.
■ Glucocorticoid insufficiency This inju ry m ay not have been an obviou s intraop erative
This problem m ay occur if hypercortisolism w ith suppres- event if only a su perior polar vessel w as ligated .
sion of the hypophyseal–pituitary–adrenal axis is not recog-
nized preoperatively and the patient is not adequately
supplemented w ith corticosteroid s perioperatively. Insuffi-
■ Hypotension
ciency w ill also occur after bilateral ad renalectom y if not This com p lication can follow resection of p heochrom ocy-
actively prevented and appropriately treated . Glucocorti- tom a. Overall lability inclu d ing hyp otension is m inim ized
coid insufficiency should be consid ered after ad renalectomy by ad equate preoperative pharm acologic p reparation to
in any patient who develops hypotension, hyponatremia, d ecrease vasoconstriction and card iac afterload w hile vol-
hyperkalemia, hypoglycemia, and acidosis. If suspected, the u m e exp ansion occu rs. Ad equ ate intraop erative resu scita-
problem should be treated immediately with intravenous tion is also critical. Decisions abou t ongoing p ostop erative
hydrocortisone. Patients at risk shou ld receive 100 m g IV invasive blood p ressu re m onitoring can be m ad e in the
recovery room . Som etim es, vasoactive p ressor therap y, ■ Subphrenic abscess
includ ing intravenous neosynephrine, norep inephrine, or
vasopressin, is requ ired u ntil regu latory hom eostasis is Abscess is a rare com plication usu ally lim ited to extensive
restored . H ow ever, many patients are quite stable after resections of large ad renal tum ors or the occasional patient
resection of p heochrom ocytom a and m ay not requ ire w ith Cu shing’s synd rom e. Abscess can u su ally be treated
observation in the intensive care u nit setting. w ith p ercu taneou s rad iologic p lacem ent of a d rain. A con-
tribu tion from postoperative pancreatitis or pancreatic leak
should be ru led out.
■ Ileus
Ileus m ay occu r w ith op en approaches, su ch as the anterior ■ Wound infection
and thoracoabd om inal approaches, but is less com m on Becau se of the increased likelihood of this com p lication in
w ith p osterior and laparoscopic approaches. Ileu s com - p atients w ith hypercortisolism com pared to those w ith
bined w ith fever and evid ence of system ic inflam m ation other ind ications for ad renalectom y, p rop hylactic antibi-
shou ld raise the su sp icion of trocar or cau tery inju ry to otics are ind icated .
intestines.
■ SUMMARY
■ Mineralocorticoid insufficiency
Although m inim ally invasive ap proaches to ad renalec-
Most p atients d o not rou tinely requ ire corticosteroid or tom y have provid ed m ost patients u nd ergoing operation
electrolyte replacem ent except in the instances mentioned . for a benign ad renal tu m or a w ell-tolerated , accelerated
Mild p ostop erative hyp erkalem ia can be seen in the d ays recovery, this fact belies the broad sp ectru m of ad renal d is-
follow ing resection of an ad renal tu m or causing hyperal- eases and d ifficu lt su rgical m anagem ent d ilemm as. It is
d osteronism . A rare patient m ay experience transient min- critical for any su rgeon caring for these p atients to have a
eralocorticoid d eficiency, w hich can be corrected w ith oral thorou gh u nd erstand ing of ad renal d iseases as w ell as
flud rocortisone 0.1 m g d aily. Patients und ergoing bilateral op tions for treatm ent. It is only w ith ju d iciou s ap plication
ad renalectom y often requ ire 0.1 to 0.2 m g flud rocortisone of any of these techniqu es to p atients that one can p revent
per d ay once the glu cocorticoid d oses have been w eaned to com p lications and im p rove p atient ou tcom es.
d aily physiologic requirem ents.
■ REFERENCES
■ Nelson syndrome 1. Bru nt LM, Doherty GM, N orton JA, et al. Lap aroscop ic ad renalectom y
com pared to op en ad renalectom y for benign ad renal neop lasm s. J Am
This is a u niqu e com p lication of bilateral total ad renalec- Coll Surg 1996;183:1–10.
tom y for Cu shing’s d isease that affects approxim ately 30% 2. Prinz R. A com parison of lap aroscop ic and op en ad renalectom ies. Arch
of long-term su rvivors. N elson synd rom e is characterized Surg 1995;130:489–494.
3. Conn JW. Prim ary ald osteronism : a new clinical synd rom e. J Lab Clin
by ongoing p itu itary enlargem ent and cutaneou s pigm en- Med 1955;45:3–17.
tation related to ACTH hyp ersecretion. The synd rom e can 4. Blu m enfeld JD, Sealey JE, Schlu ssel Y, et al. Diagnosis and treatm ent of
be prevented in som e patients by pitu itary irrad iation. p rim ary hyperald osteronism . Ann Intern Med 1994;121:877–885.
5. Fund er JW, Carey RM, Fard ella C, et al. Case d etection, d iagnosis, and
treatm ent of patients w ith prim ary ald osteronism : an end ocrine society
clinical practice gu id eline. J Clin Endocrinol Metab 2008;93:3266–3281.
■ Pneumonia 6. Angelini L, Bezzi M, Chiarot M, et al. Primary hyperaldosteronism caused
by monolateral adrenal hyperplasia. Minerva Chir 1995;50:131–137.
Pneu m onia is an u nu su al com plication w ith less invasive 7. White ML, Gau ger PG, Doherty GM, et al. The role of rad iologic stu d -
approaches, bu t it can occu r in the setting of significant ies in the evaluation and m anagem ent of prim ary hyperald osteronism .
postoperative p u lm onary com p rom ise associated w ith a Surgery 2008;144:926–933.
8. N iem an LK, Biller BM, Find ling JW, et al. The d iagnosis of Cu shing’s
thoracoabd om inal or other extensive open ap proach. Pu l- synd rom e: an End ocrine Society Clinical Practice Gu id eline. J Clin
monary infection is treated as a nosocom ial infection w ith Endocrinol Metab 2008;93:1526–1540.
app rop riate antibiotic therapy. 9. Favia G, Boscaro M, Lum achi F, et al. Role of bilateral ad renalectom y in
Cu shing’s d isease. World J Surg 1994;18:462–466.
10. H aw n MT, Cook D, Deveney C, et al. Qu ality of life after lap aroscop ic
bilateral ad renalectom y for Cu shing’s d isease. Surgery 2002;132:
■ Pneumothorax 1064–1068.
11. Grabner P, Hauer-Jensen M, Jervell J, et al. Long-term results of treatment
Pneu m othorax is a potential com plication of thoracoab- of Cushing’s disease by adrenalectomy. Eur J Surg 1991;157:461–464.
d om inal or p osterior approaches, but it shou ld be consid - 12. Greenblatt DY, Shenker Y, Chen H . The u tility of m etaiod obenzyl-
ered if any ad renalectom y by any approach requires gu anid ine (MIBG) scintigrap hy in p atients w ith p heochrom ocytom a.
Ann Surg Oncol 2008;15:900–905.
significant d issection arou nd the d iaphragm atic crus. If the 13. Misku lin J, Shulkin BL, Doherty GM, et al. Is p reop erative 123I MIBG
problem is of significant size and physiologic im p act, it scintigrap hy rou tinely necessary before initial ad renalectom y for
need s to be treated w ith tube thoracostom y. The need for pheochrom ocytom a? Surgery 2003;134:918–923.
14. Fernand ez-Cru z L, Saenz A, Benarroch B, et al. Does horm onal fu nc-
this is u su ally short-lived u nless p u lm onary p arenchym al tion of the tu m or influ ence the ou tcom e of lap aroscop ic ad renalec-
injury has occu rred . tom y? Surg Endosc 1996;10:1088–1091.
15. Fernand ez-Cruz L, Saenz A, Ku riansky J, et al. Lap aroscop ic ad renalec- 27. Zeiger MA, Thom p son GB, Du h QY, et al. AACE and AAES m ed ical
tom y for p heochrom ocytom a. Acta Chir Austriaca 1999;31:203–206. gu id elines for the m anagem ent of ad renal incid entalom as. Endocr Pract
16. Gagner M, Breton G, Pharand D, et al. Is lap aroscop ic ad renalectom y 2009;15:1–20.
ind icated for pheochrom ocytom as? Surgery 1996;120:1076–1080. 28. Kebebew E, Sip perstein AE, Clark OH , et al. Resu lts of lap aroscop ic
17. Shen WT, Sturgeon C, Clark OH , et al. Shou ld p heochrom ocytom a size ad renalectom y for su spected and u nsu sp ected m alignant ad renal neo-
influ ence su rgical ap p roach? A com p arison of 90 m alignant and 60 p lasm s. Arch Surg 2002;137:948–953.
benign pheochrom ocytom as. Surgery 2004;136:1129–1137. 29. Stu rgeon C, Shen WT, Clark OH , et al. Risk assessm ent in 457 ad renal
18. Wilhelm SM, Prinz RA, Barbu AM, et al. Analysis of large versu s sm all cortical carcinom as: how m u ch d oes tum or size p red ict the likelihood
pheochrom ocytom as: op erative ap p roaches and p atient ou tcom es. of m alignancy? J Am Coll Surg 2006;202:423–430.
Surgery 2006;140:553–559. 30. Lee J, El-Tam er M, Schifftner T, et al. Op en and lap aroscop ic ad renalec-
19. N eu m ann H P, Bausch B, McWhinney SR, et al. Germ -line m u tations in tom y: analysis of the N ational Su rgical Quality Im provem ent Program .
nonsynd rom ic p heochrom ocytom a. N Engl J Med 2002;346:1459–1466. J Am Coll Surg 2008;206:953–959.
20. Bilim oria KY, Shen WT, Elaraj D, et al. Ad renocortical carcinom a in the 31. Sau nd ers BD, Wainess RM, Dim ick JB, et al. Trend s in u tilization of
United States: treatm ent u tilization and p rognostic factors. Cancer 2008; ad renalectom y in the United States. H ave ind ications changed ? World J
113:3130–3136. Surg 2004;28:652–658.
21. Dackiw APB, Lee JE, Gagel RF, et al. Ad renal cortical carcinom a. World 32. Walz MK, Alesina PF, Wenger FA, et al. Posterior retrop eritoneoscop ic
J Surg 2001;25:914–926. ad renalectom y—results of 560 proced u res in 520 patients. Surgery 2006;
22. Terzolo M, Angeli A, Fassnacht M, et al. Ad ju vant m itotane treatm ent 140:943–948.
for ad renocortical carcinom a. N Engl J Med 2007;356:2372–2380. 33. Walz MK, Peitgen K, H oerm ann R, et al. Posterior retrop eritoneoscop y
23. Sabolch A, Feng M, Griffith K, et al. Ad ju vant and d efinitive rad iother- as a new m inim ally invasive ap p roach for ad renalectom y: resu lts of 30
ap y for ad renocortical carcinom a [p u blished online ahead of p rint Ju ly ad renalectom ies in 27 p atients. World J Surg 1996;20:769–774.
31, 2010]. Int J Radiat Oncol Biol Phys. 34. Walz MK, Groeben H , Alesina PF. Single-access retrop eriton eoscop ic
24. Miller BS, Am m ori JB, Gau ger PG, et al. Lap aroscop ic resection is inap - ad renalectom y (SARA) versu s convention al retrop eriton eoscop ic
propriate in p atients w ith know n or su sp ected ad renocortical carci- ad renalectom y (CORA): a case-con trol stu d y. World J Surg 2010;34:
nom a. World J Surg 2010;34:1380–1385. 1386–1390.
25. Bellantone R, Ferrante A, Boscherini M, et al. Role of reop eration in 35. Walz MK, Peitgen K, Diesing D, et al. Partial versu s total ad renalec-
recu rrence of ad renal cortical carcinom a: resu lts from 188 cases col- tom y by the p osterior retrop eritoneoscop ic ap p roach: early and long-
lected in the Italian national registry for ad renal cortical carcinom a. term resu lts of 325 consecu tive p roced u res in p rim ary ad renal
Surgery 1997;122:1212–1218. neop lasias. World J Surg 2004;28:1323–1329.
26. Lee JE, Evans DB, H ickey RC, et al. Unknow n p rim ary cancer present- 36. Perrier N D, Kennam er DL, Bao R, et al. Posterior retrop eritoneoscop ic
ing as an ad renal m ass: frequ ency and im plications for d iagnostic eval- ad renalectom y: p referred technique for rem oval of benign tu m ors and
uation of ad renal incid entalom as. Surgery 1998;124:1115–1122. isolated m etastases. Ann Surg 2008;248:666–674.
CHAPTER
42
Complications of Thyroid and
Parathyroid Surgery
Gerard Doherty
■ INTRODUCTION hyp erfu nctional? and (2) Is the nod u le m alignant? All
p atients have a thorou gh history and p hysical exam ina-
Thyroid and parathyroid operations are generally safe pro- tion, w ith a focu s on the p ersonal history of thyroid d is-
ced ures w ith rare life-threatening com plications. While the ease and rad iation exp osu re, the fam ily history of thyroid
com plications com m on to any operation, su ch as bleed ing, d iseases, and the p hysical featu res in the neck inclu d ing
infection, and anesthetic reactions can occu r, they are all regional ad enop athy. An u ltrasou nd evalu ation of the thy-
qu ite u nu su al. Bleed ing d u ring the proced u res is lim ited , roid is a p art of the p hysical exam ination and shou ld
and alm ost never is sufficient blood lost to require transfu - accom p any all thyroid nod u le evalu ations. Patients w ith
sion. Bleed ing follow ing the p roced ure can cau se d anger- p ersonal history of therap eu tic or accid ental (bu t not
ous local effects, bu t still rarely requires blood replacement. ap p arently d iagnostic) d oses of rad iation exp osu re
The neck is a p rivileged site for w ound healing, w ith a ( 2,500 cGy) to the thyroid have an increased risk of both
robu st blood su pply to the skin and soft tissue that can thyroid nod u les and thyroid cancer, w ith a latency of tw o
w ithstand su bstantial contam ination w ithou t clinical infec- to fou r d ecad es; this inform ation can change the d iagnos-
tion. These p roced u res are typically perform ed as am bu la- tic schem e and in p articu lar lead s m ost su rgeons to
tory or overnight hospitalizations, w ith short (1–3 hou rs) rem ove the entire thyroid if any op erative p roced u re is
general, or regional, anesthetic techniqu es, thu s lim iting necessary (1–3). A fam ily history of thyroid d isease is very
the risk of anesthetic or p u lm onary com plications, and com m on and m ay inclu d e a variety of benign or m alignant
d eep venou s throm botic events. d iagnoses w ithin one fam ily. Often, d ifferent fam ily m em -
In sp ite of these features, cervical end ocrine surgery is bers have m u ltinod u lar goiter, p ap illary thyroid cancer,
consid ered a d elicate, somew hat risky area of clinical p rac- Graves d isease, or H ashim oto thyroid itis in a variety of
tice. Significant technical com plications can occu r that can first-d egree relatives. These fam ilies seem to have a
create p erm anent, life-altering changes to patient fu nction. p red ilection to d evelop any one of several thyroid cond i-
The m ost com m on of these are hypoparathyroid ism and tions. In ad d ition, there are sp ecific heritable genetic
nerve injury. Other less frequent complications include cervi- d efects that can p red isp ose to p ap illary (Fam ilial Ad eno-
cal hematoma and aerodigestive tract damage. Finally, failure m atou s Polyp osis—APC gene) or m ed u llary (Mu ltip le
of the op erative strategy to fulfill its goals, as w ith persistent End ocrine N eop lasia Typ e 2 synd rom es—Ret p roto-onco-
hyperparathyroid ism, can complicate overall patient care. gene) thyroid cancers. Evid ence of these abnorm alities
shou ld p rom p t fu rther evalu ation and genetic cou nseling.
■ THYROID SURGERY Thyroid ultrasound ad d s very useful information in the
evalu ation of thyroid nod u les (4–6). It can accu rately char-
Thyroid op erations are p erform ed to m anage actual or acterize the size, nature (solid vs. cystic), and textu re
p otential m alignancy, thyroid hyperfu nction, or thy- (homogeneous, macro- or microcalcifications, smooth or
rom egaly p rod ucing local sym ptom s from com pression of irregular m argins) of the ind ex nod ule, as w ell as the
surrou nd ing stru ctu res. The ind ications and strategies for rem aind er of the thyroid gland . As the thyroid gland can be
these proced ures are consid ered in their clinical contexts. d ifficult to reprod ucibly and accurately investigate on phys-
ical exam ination alone, ultrasound is critical. Ultrasound
■ Diagnostic thyroid evaluation can also be used to guid e tissue sampling. Thyroid function
tests, specifically inclu d ing thyroid -stimulating hormone
The d iagnostic evalu ation of a thyroid nod u le ad d resses
(TSH ) and tetraiod othyronine (T4) levels, d emonstrate the
tw o issu es: (1) Is the nod u le or the rem aining thyroid
status of the pituitary–thyroid axis and the physiologic
appropriateness of thyroid hormone prod u ction. N otably,
Gerard Doherty: N .W. Thom p son Professor of Su rgery; the only clinical situation in w hich thyroid scintigraphy
Vice-Chair, Departm ent of Su rgery; University of Michigan, (nuclear med icine scanning) is currently useful in the d iag-
Ann Arbor, Michigan nostic evaluation of a thyroid nod ule is w hen the patient is
550
Chapter 42 • Complications of Thyroid and Parathyroid Surgery 551
hyperthyroid (6–8). It allow s d istinction betw een a hyp er- Table 4 2 .2 Cla ssifi ca t ion of t hyroid ca rcin om a
functioning nod ule w ith suppressed surround ing thyroid
parenchyma and a neop lastic nod u le in Graves d isease. Cell of Origin Tumor Type Subtypes
For the m ost typical p atient, w ho is euthyroid w ith a Follicular cell Papillary Classic
d om inant solitary nod u le, the m ainstay of the d iagnostic Follicular variant
evalu ation is fine-need le aspiration cytology (6–10). This Tall cell
proced u re is d one in the clinic, often und er u ltrasou nd Diffuse sclerosing
Follicular Minimally invasive
gu id ance, and p rovid es the best inform ation to ad d ress
Hürthle cell
w hether the nod u le is m alignant. The potential resu lts are
Insular
(a) m alignant, p rom pting specific therapy; (b) benign, Anaplastic
prom p ting interval follow -u p evaluation for m ost p atients;
C-cell Medullary
(c) insu fficient sam ple, prom pting repeat need le asp iration
cytology; and (d ) ind eterm inate. Ind eterm inate asp irations Lymphocyte Lymphoma
im ply that there is ad equ ate cellu lar m aterial for assess-
ment, bu t that the d iagnosis is u ncertain becau se of the
natu re of the lesion. This frequently occurs w ith follicu lar
lesions of the thyroid gland . In this clinical situ ation, the sym p tom atic lesion s, th yroid lobectom y can be the
best next step is typ ically a d iagnostic thyroid resection. th erap eu tic p roced u re of ch oice an d carries risks sim ilar
The minimum appropriate proced ure for assessing the to d iagn ostic lobectom y. For m ost p atien ts requ irin g
natu re of a potentially m alignant thyroid lesion is lobec- therapeutic thyroidectomy, how ever, the procedure involves
tomy and isthmusectomy (11–14). This should includ e some resection of both lobes of th e th yroid glan d (total
gross m argin of normal thyroid gland betw een the line of thyroid ectom y).
d ivision and the lesion in question. The complications of
removing one sid e of the thyroid gland are similar to the Thyroid Carcinoma
complications of total thyroid ectomy, w ith some important Thyroid carcinoma can be categorized based u pon the cell
d istinctions. First, as a single functional parathyroid gland of origin and the grow th p attern of the tu m or (Table 42.2).
is su fficient to m aintain norm al p arathyroid control of The follicu lar cell–d erived thyroid cancers are by far the
calcium flux and there are parathyroid gland s on each sid e m ost com m on, and the bu lk of these ( 75%) are w ell-
of the larynx, it is not p ossible to p rod u ce p erm anent d ifferentiated p ap illary thyroid cancers w ith an excellent
hypoparathyroid ism by thyroid lobectom y. Second , w hile long-term su rvival. A variety of p rognostic scoring system s
inju ry to the ipsilateral recu rrent laryngeal nerve (RLN ) can are available to categorize the p robable p atient outcom e.
prod u ce p ermanent voice changes, thyroid lobectomy d oes One of the m ost u sed , and easiest to ap p ly becau se the
not carry a risk of bilateral recu rrent nerve injury and conse- inform ation is available soon after resection, is the MACIS
qu ent airw ay occlusion. Finally, for m ost patients w ho system (Table 42.3) (15). There is a su bgrou p of p atients
require only unilateral thyroid ectomy, there is no need for that com prise the very best prognosis lesions: w om en 45
thyroid hormone replacement therapy, thus eliminating the years of age, w ith tu m ors that m easu re ( 10 m m in d iam e-
possibility of iatrogenic hyper- or hypothyroid ism. ter and that are confined entirely to the thyroid gland , w ith
no thyroid cap su le invasion or lym p h nod e m etastasis. All
investigators agree that this grou p of p eop le d oes not bene-
■ Therapeutic thyroidectomy fit from the ad d itional d issection d one for a total thyroid ec-
Thyroid ectom y has a m ajor role in the therap y of several tom y and can be treated by thyroid lobectom y (12,16–18).
thyroid p rocesses (Table 42.1). For patients w ith u nilateral, For m ost p atients, how ever, there is som e ad vantage to
total thyroid ectom y, m ainly in im p roved d isease-free su r-
vival thou gh there are also d ata to su p p ort an overall
Table 4 2 .1 Th erapeu tic thyroidectomy in dication s m ortality ad vantage (18). Im p roved d isease-free survival
releases the patient from the need for ad d itional episod es
Thyroid lobectomy of care and the associated p otential sid e effects, com p lica-
Solitary toxic nodule tions, and tim e lost. The m agnitu d e of the ad vantage is
Unilateral benign adenoma or cyst producing local symptoms
m ore su bstantial for som e grou p s than others. In general,
Best-prognosis thyroid cancers
being old er, m ale, having a larger tu m or, and having
Total thyroidectomy sp read of d isease ou tsid e of the thyroid gland , each ind i-
Most thyroid carcinoma vid u ally correlate w ith having a greater risk of recu rrence
Graves disease
and / or d eath. These p atients benefit from total thyroid ec-
Hashimoto’s thyroiditis
tom y, and fu rther ad ju vant therap y w ith rad ioiod ine and
Toxic multinodular goiter
Symptomatic multinodular goiter thyroid horm one su p p ression of TSH (6,12,16).
Substernal goiter (most) For anap lastic can cer an d lym p h om a, the role of
op erative in terven tion is m ain ly for d iagn osis, alth ou gh
Table 4 2 .3 M ACIS t hyroid ca n cer p rogn osis cla ssifi ca t ion syst em (15)
Acronym Feature Score
M Metastasis Add 3.0 if distant metastasis present
A Age Add 3.1 if age 40 years,
Or
Add 0.08 age
C Completeness of surgical resection Add 1.0 if the surgical resection leaves gross
tumor in place
I Invasiveness (local) Add 1.0 if there is local extrathyroidal invasion
by tumor
S Size Add 0.3 tumor size
Predicted 20-Year Cause-Specific
Patient Total Score Survival from Mayo Clinic Data (%) Fraction of Total Group (%)
6.0 99 80
6.0–6.9 89
7.0–7.9 56
8.0 24 5
occasionally for p alliative resection (19–21). In these sp e- d em ineralization as an effect of their hyp erthyroid ism .
cific situ ations, the tum or is often qu ite extensive, and so After op eration, they can have an acu te d rop in seru m lev-
incisional biopsy to sup ply tissue for pathologic analysis is els of calciu m requ iring rep lacem ent, w hich is som etim es
appropriate (in contrast to d iagnostic lobectom y, above). accompanied by an early fall in serum parathyroid hormone
Anaplastic thyroid carcinom a is an extremely aggressive, (PTH ), and subsequent rise of PTH to supernorm al levels
poorly d ifferentiated tum or d erived from thyroid follicu lar (tem p orary second ary hyp erp arathyroid ism ). It ap p ears
cells. Resection is often not possible and even w hen p ossi- that both a sud d en correction of the hyperthyroid ism and
ble is typ ically u nsu ccessfu l at controlling this rap id ly some insult to the parathyroid gland s are necessary for the
progressive p rocess. Lym phom a is generally treated by follow ing reasons: (a) sim ilar hypocalcem ia d oes not follow
rad iation and chem otherap y after the d iagnosis and cell rad ioiod ine therapy for Graves d isease, w hen the d ecrease
typ e are secu re. in hyp erthyroid ism is m u ch slow er; and (b) there is no
hypocalcemia after thyroid lobectomy for toxic ad enoma,
Graves Disease w hen tw o parathyroid gland s have been left und isturbed .
Graves d isease is an au toim m une cond ition, in w hich stim - Goiter
ulated au toantibod ies form against the TSH recep tor on
Goiter is a general term for an enlarged thyroid and is u su -
thyroid cells. These antibod ies stim u late the thyroid gland
ally reserved for benign p rocesses that d iffu sely affect the
to grow and to overprod uce thyroid horm one. The thera-
peu tic op tions for Graves d isease inclu d e rad ioiod ine ther-
apy (by far the m ost com m on treatm ent chosen in the
Table 4 2 .4 In d ica t ion s for op er a t ive t h er a py
United States), chronic antithyroid m ed ications (prop ylth-
in G r aves d isea se
iou racil or m ethim azole), or total thyroid ectom y. Total thy-
roid ectom y is a very effective strategy for Graves d isease Increased radioiodine risk
and has the ad vantage of resolving the issu e quickly and Pregnancy
d efinitively; repeat treatm ents are often necessary for Desire to become pregnant within 6 months
rad ioiod ine to erad icate the hyperthyroid ism . H ow ever, Childhood/adolescence
most patients w ou ld p refer the rad ioiod ine ap proach in Decreased effectiveness of therapeutic radioiodine
ord er to avoid the p ain, scar, and potential com plications of Large goiter
operation. There are som e clinical situ ations, how ever, Severe thyrotoxicosis requiring rapid control
w hen rad ioiod ine therap y is contraind icated or less d esir- Amiodarone-induced thyrotoxicity
able than resection (Table 42.4). Associated conditions
The com p lications of total thyroid ectom y for Graves Coexistent suspicious thyroid nodule
d isease are u niqu e only in the frequ ent severity of th e Coexistent hyperparathyroidism
hyp ocalcem ia that can follow th e op eration (22–24). Patient preference
Patients w ith Graves d isease often have significant bone
gland . The gland m ay be norm ally active, hyp eractive, or evacu ation at th e bed sid e, th is p ossibility exists
hyp oactive. The goiter can resu lt from any of several w ith every n eck hem atom a. Patien ts w ith a sign ificant
p rocesses, inclu d ing generalized hyp erp lasia, m u ltip le hem atom a of th e n eck sh ou ld n ot be left alone u n til th e
hyp erp lastic nod u les, or H ashim oto thyroid itis. The m ost hem atom a h as been evacu ated . Med ical p ersonn el w ith
com m on ind ication for resection is local com p ression of the cap ability of op ening the w ou nd to d ecom p ress the
ad jacent stru ctu res. Patients d evelop d ifficu lty sw allow ing airw ay m u st stay w ith th e p atien t u n til th e situ ation is
as the m ost frequ ent sym p tom of cervical com p ression. resolved . For m ost p atients, the hem atom a is less im m e-
Pressu re on the larynx can cau se a “tightening” of the d iately th reaten ing, and the p atient can be u rgen tly
voice, w hich sou nd s m ore high-p itched and constricted in retu rn ed to the op erating room , p laced u nd er anesthesia,
range than u su al for the p atient; the p atient is often m ore an d th e hem atom a then evacu ated and bleed in g con -
sensitive to this than those arou nd them . This voice trolled . Often, no sp ecific bleed ing site can be id entified
change is from laryngeal com p ression rather than effects at reop eration, alth ou gh w h en on e is fou nd , th e m ost
on the RLN . Tru e hoarseness from nerve com p ression w ith likely areas are the anterior ju gu lar veins u nd er the
vocal cord p aralysis is u nu su al w ith benign cond itions p latysm a flap s, th e su p erior p ole vascu lar p ed icle, and
and shou ld raise su sp icion of u nrecognized m alignancy. the vessels of the ligam ent of Berry, ad jacent to the RLN
Enlargem ent of a su bsternal goiter is m ore likely to cau se insertion. Carefu l hem ostasis d u ring the initial op eration
com p ression of the trachea. Patients m ay com p lain of d iffi- is ju stified , w ith p articu lar attention to these areas, to try
cu lty breathing w ith exercise, as p eak airw ay flow is lim - to p revent this com p lication.
ited , or m ay d evelop sym p tom s w hen recu m bent in a The risk of cervical hem atom a has led som e to qu estion
su p ine p osition, as the trachea is fu rther com p ressed by the safety of ou tp atient thyroid ectom y becau se there
the w eight of the anterior m ed iastinal thyroid (25). w ou ld be som e p ossibility of the hem atom a d evelop ing
The resection for goiter is p lanned to relieve the local after d ischarge (26–30). The cu rrent exp erience w ith ou tpa-
com p ressive sym ptom s. This is generally very su ccessfu l, tient thyroid su rgery by exp erts in the field has d em on-
thou gh the tem p orary ed em a follow ing op eration m ay strated that this can be d one safely, thou gh p ostop erative
mask the im p rovem ent for several w eeks. Resection carries observation for 6 hou rs is rou tine, in ord er to d etect this
all of the sam e com plication risks as operation for other com plication p rior to facility d ischarge.
ind ications. In ad d ition, operation for H ashim oto thyroid i-
tis can be d ifficu lt becau se of the local inflam m ation that is
inherent in the d isease. Most patients w ith H ashim oto thy-
■ Hypoparathyroidism
roid itis requ ire no therap y beyond thyroid rep lacem ent; The parathyroid glands are small, delicate structures that
resection is not rou tinely necessary. share a blood supply w ith the thyroid gland. Their diminu-
tive size (normal 30–60 mg) and fragile nature make them
particularly prone to damage during thyroidectomy. Patients
■ Potential complications of thyroidectomy w ho have markedly diminished or absent parathyroid func-
The p otential com p lications of thyroid op erations inclu d e tion after thyroidectomy have severe hypocalcemia that
the im m ed iate com p lication of cervical hem atom a, as w ell requires replacement. If permanent, this complication can be
as the m ore chronic com p lications of hyp op arathyroid ism , palliated by calcium supplements, but this requires multiple
nerve inju ry, and inju ries to the aerod igestive tract. Finally, d oses each day, and uncomfortable symptoms occur if doses
chronic p roblem s can arise from iatrogenic hyp er- or are late or missed . In ad d ition, there is cumulative bone
hyp othyroid ism . d amage over time.
The sym p tom s of hyp op arathyroid ism are those of
severe hyp ocalcem ia. Patients have nu m bness and tin-
■ Neck hematoma gling in the d istal extrem ities and arou nd the m ou th or
A neck hematoma requiring reoperation d evelops after tongu e in the earliest p hases. With m ore severe hyp ocal-
operation in about 1 of every 150 thyroid ectomies (26–30). cem ia, p atients d evelop m u scle cram p ing at rest, or esp e-
The hematoma nearly alw ays appears w ithin the initial 6 cially w ith u se. The anxiety that often accom p anies these
hours after the com p letion of the proced u re, though w ith sym p tom s exacerbates them , as the p atient hyp erventi-
anticoagu lation, the hematoma can appear up to several lates. The consequ ent resp iratory alkalosis shifts m ore cal-
d ays later. This complication is manifest by increasing pain, ciu m intracellu larly, low ering the seru m level of calciu m
neck sw elling, and often m arked anxiety. The hem atom a and w orsening the sym p tom s. Severe tetany can resu lt.
can collect either betw een the platysma muscle and the ster- Patients can then be lim ited in their ability to help them -
nohyoid m u scles (su perficial) or d eep to the strap m uscles selves resolve the ep isod e w ith calciu m su p p lem ents, as
along the larynx (d eep). The d eep hematom as are the more their hand s and forearm s are often severely affected by the
d angerou s, as they can be sequestered on one sid e of the lar- m u scle sp asm s.
ynx cau sing a shift and compression of the airw ay. The classic signs of hypocalcemia are Chvostek sign and
While a m inority of p atients w ith p ostop erative Trou sseau sign. Chvostek sign is generated by tapp ing gen-
hematomas develop airw ay compromise requiring emergent tly over the facial nerve in the lateral cheek to d em onstrate
facial muscle contraction d ue to increased nerve irritability. Intravenous calcium gluconate is the only option for calcium
This sign is present in some minority of people w ith a nor- supplementation. Calcium chlorid e can cause severe tissue
mal serum level of calcium and so is not entirely reliable in d am age if accid ental tissu e infiltration occu rs and shou ld
the d iagnosis of hypocalcemia, but can be helpful in follow - never be u sed ou tsid e of an acu te, life-threatening card iac
ing levels in som e p eop le. Trou sseau sign is elicited by placem ergency. Bolu s ad m inistration of calciu m glu conate
ing a sphygm om anom eter cu ff on the u pper arm and (su p p lied in 1,000-m g am p u les containing 90 m Eq cal-
inflating to systolic p ressure. Within a few m inutes, the ciu m ) corrects seru m levels of calciu m rap id ly and safely,
patient d evelops severe carpal spasm, w ith flexion of the thou gh the effect is short-lived . An alternative is to u se
w rist and fingers and abd uction of the thumb. This sign is a calciu m glu conate solu tion (six am p u les of calciu m
very uncomfortable for the patient and should not be used glu conate 6 g calciu m glu conate 540 m Eq calciu m in
clinically. In general, the symptoms of hypocalcemia are 500 m L D5W) infu sed at 1 m L/ kg/ h. This p rovid es a
much more reliable and useful for patient assessment than stead y calciu m su p p lem ent and can be ad ju sted to m ain-
the signs. tain the calciu m in the norm al range w hile oral su p p le-
The acu te m anagem ent of hyp ocalcem ia in the p ostop - m ents are absorbed .
erative patient d epend s upon the severity of the hypocal- Tem porary hypocalcemia occurs in about 10% of patients
cem ia and sym p tom s. Total serum calciu m levels correlate after total thyroid ectom y, and p erm anent hyp ocalcem ia in
roughly w ith sym p tom s, but are qu ite variable betw een abou t 1% (Table 42.5) (31–37). The tem p orary hyp ocal-
ind ivid u als. Some p atients can have extrem ely low total cem ia can be severe and requ ires intravenou s and oral
serum levels of calciu m w ith no sym ptom s, w hile others su p p lem entation for the d u ration of the effect. Perm anent
can have severe sym ptom s and signs, w ith nearly norm al hyp op arathyroid ism requ ires lifelong su p p ort w ith cal-
calciu m levels. Ionized calciu m m easurem ents correlate ciu m su p p lem ents and vitam in D analogs. Missing d oses
better than total seru m calcium levels, bu t there is still vari- of the su p p lem ents w ill u su ally p rod u ce sym p tom s of
ability. Rep lacem ent is generally guid ed by sym ptom s. For varying severity and w hich, w hile m anageable, are often
mild hyp ocalcem ia w ith tingling, oral calcium su p p le- qu ite both ersom e for p atien ts. In ad d ition to th e d iscom -
ments (calciu m carbonate, 500 to 1,500 m g p.o., tw o to fou r fort an d in con ven ience of th e su p p lem en ts, p atients
tim es d aily) are often su fficient to resolve the hyp ocal- d evelop low -tu rnover bone d isease, w hich resem bles
cem ia. Daily d oses of calciu m 3,000 m g p rovid e little osteom alacia. Thou gh d ysm orp hic, bone m ass is generally
increm ental benefit, how ever, becau se of the lim its of gas- p reserved or increased in hyp op arathyroid ism , and frac-
trointestinal absorp tion of calcium . If su pplem entation tu re risk is not ap p arently increased (38). Finally, the cal-
beyond this level is necessary (as it is for m ost patients w ith ciu m and vitam in D su p p lem ents w ith low PTH lead to an
severe hyp ocalcem ia), then the ad d ition of su pplem ental increased d aily u rinary excretion of calcium and signifi-
vitam in D (calcitriol 0.25 to 1.0 g d aily) increases the gas- cant risk or nep hrolithiasis.
trointestinal absorp tion of calcium . Vitam in D requ ires The recent availability of p harm acologic PTH for exoge-
48–72 hou rs to have its effect, how ever, and so intravenou s nou s ad m inistration has op ened the op p ortu nity to rep lace
calciu m su p p lem entation m ay be need ed u ntil then. Antic- PTH in p atients w ith p ostop erative hyp op arathyroid ism .
ipation of the need for vitam in D can smooth the patient The exp erience w ith this to d ate is lim ited , bu t early results
management consid erably by starting it early. d em onstrate that PTH d elivered su bcu taneou sly tw ice
H ypocalcem ia not controlled by oral supplements, or d aily can m aintain seru m calciu m levels in the sam e range
accompanied by severe symptoms such as muscle cramping, as oral calciu m and vitam in D su p p lem ents and d ecreases
is best managed by intravenous calcium administration. the am ou nt of hyp ercalciu ria (39,40). Fu rther experience
Table 4 2 .5 In cid en ce of com p lica t ion s a ft er t ot a l t hyroid ect om y

Transient Nerve Permanent Nerve Transient Hypo- Permanent Hypo-
Authors, Year Number of Patients Paresis, N (%) Paresis, N (%) parathyroidism, N (%) parathyroidism, N (%)
Thompson et al., 1978 (32) 165 NR 0 NR 2%
Farrar et al., 1980 (31) 29 NR 1 (3%) 2 (7%) 4 (14%)
Schroder et al., 1986 (33) 56 1 (2%) 0 9 (17%) 3 (6%)
Clark et al., 1988 (34) 160 4 (2.5%) 3 (2%)a NR 1 (0.6%)
Ley et al., 1993 (35) 124 1 (0.8%) 1 (0.8%) 13 (10%) 2 (1.6%)
Tartaglia et al., 2003 (36) 1,636 31 (1.9%) 15 (0.9%) NR 14 (0.9%)
Rosato et al., 2004 (37) 9,599 195 (2%) 94 (1%) 797 (8.3%) 163 (1.7%)
NR, not reported.

a
Each from deliberate sacrifice of the recurrent laryngeal nerve due to tumor involvement.
Cricothyroid Superior parathyroid gland

muscle
Common
carotid artery
Internal
jugular vein
Inferior
thyroid artery
Recurrent
laryngeal nerve
B
04
er'
h Inferior parathyroid gland
F isc
HR
A
Recurrent
laryngeal
nerve
Parathyroid
gland
Inferior
thyroid artery
Inferior thyroid vein

C
FIGURE 42.1. Relationship and dissection of the parathyroid gland blood supply and the recurrent laryngeal nerve
(RLN). A: Once the upper pole vessels have been divided and the thyroid lobe has been reflected anteriorly, dissection of
the tracheoesophageal groove exposes the blood supply to the parathyroid glands. The glands are usually entrapped
under adherent soft tissue stretched across the surface of the thyroid gland. The parathyroid dissection begins along the
edge away from its blood supply, and the parathyroid glands are released back toward the carotid artery (arrows). B: The
RLN is identified below the inferior thyroid artery, at or below the level of the lower pole of the thyroid gland. The nerve is
predictable in its position at this level, in the groove between the trachea and esophagus (easily identified if a stethoscope
or temperature probe is in the lumen). The RLN is not tethered by any attachments at this level and so can be dissected with
less danger of injury. The nerve dissection then continues superiorly to the inferior thyroid artery. The inferior thyroid artery
branches can then be divided with the nerve in full view, to ensure the safety of the dissection. C: Once the inferior thyroid
artery branches have been divided and the thyroid separated from the dense attachments to the trachea near the level of
the RLN insertion under the cricopharyngeal muscle, the lower pole vessels can be divided safely.
w ith this strategy w ill be necessary before the fu ll long- branches shou ld be d ivid ed d istal to the branching of the
term effects are clear. p arathyroid end arteries. The p arathyroid gland s can then
Avoid ance of p erm anent hyp op arathyroid ism is far be moved p osteriorly in the neck aw ay from the thyroid , to
more d esirable than treatm ent of it. This can be accom - allow safe d issection of the RLN and thyroid attachm ents
plished by p reservation of the parathyroid gland s on their to the trachea.
native blood su p ply, or autografting of parathyroid tissu e If the p arathyroid gland s cannot be p reserved on their
to a m u scu lar bed (41). Du ring thyroid ectom y, the blood native blood su p p ly, then transfer of the gland to a con-
su p p ly to each p arathyroid gland shou ld be id entified and venient grafting site can m aintain fu nction (25,41). For
specifically consid ered d uring d issection. Every p arathy- norm al p arathyroid gland s, transfer to the sternocleid o-
roid gland shou ld be treated as thou gh it w ere the only m astoid m u scle p rovid es a convenient vascu lar bed for
rem aining gland . The parathyroid gland s receive their transp lant (Fig. 42.2). The p arathyroid gland m u st be
blood su p p ly via the inferior thyroid artery (Fig. 42.1). Du r- red u ced to p ieces that can su rvive on the d iffu sion of
ing d issection of the thyroid , the inferior thyroid artery nu trients tem p orarily, w hile neovascu lar ingrow th occu rs
Sternocleido-
mastoid muscle
Incisions Parathyroid
fragment
Brachioradialis
muscle
Parathyroid
Closures
gland
A B D
FIGURE 42.2. Parathyroid autograft: If a parathyroid gland has been devascularized during dissection, then the best
management is to autograft the gland. In addition, there are certain conditions (e.g., familial parathyroid multiple gland
disease or renal osteodystrophy) for which it may be advantageous to remove the parathyroid glands from the native site
and autograft them elsewhere. A: Normal parathyroid glands can be grafted into the sternocleidomastoid muscle. As a
rule, abnormal parathyroid glands should not be autografted back into the neck, but rather grafted to a distant location,
such as the nondominant forearm. Transverse incisions over the brachioradialis muscle heal much better than longitudi-
nal incisions. B: The parathyroid gland is sliced cleanly into pieces 1–2 mm in maximum dimension. C: Each piece to be
grafted is placed into an individual pocket in the selected muscle. D: Each pocket is closed with a suture to prevent extru-
sion of the graft. For abnormal parathyroid glands grafted into the arm, the sites may be marked by using permanent
sutures; however, for normal glands grafted in the neck, resorbable sutures are preferable.
over several w eeks. This strategy is effective as is clear (right RLN ), and back along the tracheoesop hageal groove
from op erative series in w hich all p arathyroid gland s w ere on each sid e. They p ass betw een the thyroid and the larynx
au tografted in ord er to try to op tim ize the long-term ou t- and insert in the larynx at the inferior bord er of the
com e of norm al p arathyroid fu nction. All p atients becam e cricop haryngeal m u scle. The nerve often branches at abou t
tem p orarily hyp op arathyroid , bu t all recovered to becom e the level of the low er p ole of the thyroid and inserts to the
d ep end ent fu lly on their au tografts. While this strategy is larynx as tw o or m ore ad jacent fibers; there is also an
effective, it lead s to significant short-term m orbid ity d u e esop hageal branch that extend s posteriorly from abou t the
to the u niform , severe hyp ocalcem ia that occu rs before level of the thyroid low er pole.
graft fu nction begins. A selective strategy of au tografting Damage to the RLN causes unilateral paralysis of the
only the p arathyroid gland s that are d evascu larized d u r- muscles that control ipsilateral vocal cord tension. Unilat-
ing d issection is equ ally effective and m ore com fortable eral RLN injury changes the voice su bstantially in m ost
for the m ajority of the p atients. patients and also significantly affects the sw allow ing mech-
anism. The voice can range from a soft, w hispery voice,
w ith the inability to increase the volume at all, to a nearly
■ Nerve injuries norm al sou nd ing voice, w hich cannot be raised to a yell.
There are several nerves ad jacent to the thyroid gland that The d ifference betw een these is based on the ability of the
can be d eliberately or inad vertently affected d uring thy- contralateral vocal cord to cross the mid line and appose the
roid ectom y. These inclu d e the RLN im m ed iately ad jacent affected cord . If the cord s cannot meet, then the voice w ill be
to the thyroid and the vagu s nerve, w hich is slightly more soft and breathy. If the cord s can meet, then the speaking
rem oved , bu t cau ses the sam e sym ptom s w hen d am aged . voice w ill be more normal in timbre, but the affected cord
The external branch of the su p erior laryngeal nerve can be prolapses w ith increased airw ay pressu re, and the ability to
injured d u ring d issection of the upp er pole of the thyroid yell is lost. Sw allow ing is also affected , and the aspiration of
gland , and the sym p athetic chain and stellate ganglion can liqu id s is a m ark of severe RLN p aresis. This im proves w ith
be inju red near the p osterior aspect of the u pper pole of the time and can be helped by sw allow ing training.
gland as w ell. Bilateral RLN inju ry cau ses p aralysis of both cord s and
u su ally resu lts in a very lim ited airw ay lu m en at the cord s.
Recurrent Laryngeal Nerve These p atients u su ally have a norm al-sou nd ing sp eaking
The RLN fibers are a p art of the vagu s nerve on each sid e, voice, bu t severe lim itations on inhalation velocity becau se
until they branch off in the u pper chest, course arou nd the of u p p er airw ay obstru ction. They often requ ire reintuba-
ligam entu m arteriosu m (left RLN ) or the su bclavian artery tion to m aintain ventilation.
RLN paresis is usually tem porary and resolves over to try to lim it or avoid nerve inju ries (42,43). The d ata d o
d ays to months (Table 42.5) (31–37). There is no know n not cu rrently su p p ort the m and atory u se of these d evices,
method of aid ing or speed ing recovery. If a unilateral pare- as the risk of nerve inju ry is related to several factors
sis proves to be p erm anent, then palliation of the cord (44–46). H ow ever, m any exp erienced su rgeons now rou-
immobility and voice changes can be achieved w ith vocal tinely u se a nerve-m onitoring system intraop eratively. This
cord injection or laryngoplasty. These proced ures stiffen m ay be becau se they m erely help to id entify the nerve,
and med ialize the paralyzed cord , in ord er to allow the con- w hile the p ortion of the op eration m ost likely to p rod u ce
tralateral cord to appose the p aralyzed cord d u ring speech. d am age in exp erienced hand s is the d issection of the RLN
If both cord s are affected , then the palliative proced u res are at the fixed p oint of the cricop haryngeu s.
more limited and involve creating an ad equate airw ay for Abou t 10% of p atients have some evid ence of RLN
ventilation; improvements in voice qu ality are not likely as p aresis after thyroid ectom y; how ever, this resolves in most
there is no m uscu lar control of the cord function. p atients. Abou t 1% or few er p atients have perm anent
Avoid ance of RLN inju ry is far su p erior to p alliation. nerve inju ry w hen total thyroid ectom y is p erform ed by
Great care mu st be taken d u ring the d issection of the nerve, exp erienced su rgeons (Table 42.5).
in ord er to p rotect it. In som e clinical situ ations, the RLN is
sacrificed to allow an ad equ ate tu m or resection. Absent External Branch of the Superior Laryngeal Nerve
this u nu su al circu mstance, thou gh, careful d issection can This nerve courses adjacent to the superior pole vessels of the
generally p reserve cord function. The p rinciples of the d is- thyroid gland before separating to penetrate the cricopharyn-
section are as follow s: geus muscle fascia at its superoposterior aspect (Fig. 42.3).
The nerve su p p lies m otor innervation of the inferior con-
1. Avoid dividing any structures in the tracheoe-
strictor m uscles of the larynx. Dam age to this nerve changes
sophageal groove until the nerve is definitively identi-
the ability of the larynx to control high-p ressu re p hona-
fied. Sm all branches of the inferior thyroid artery m ay
tion , su ch as high-p itched singing (sop rano/ falsetto) or
seem like they can clearly be safely transected ; how ever,
yelling (37,47).
the d istortion of tum or, retraction, or previous scar m ay
To avoid d amaging this nerve, the d issection of the
lead the su rgeon to m istakenly d ivid e a branch of the
u pper pole vessels should proceed from a space w here the
RLN . The id entifying featu re of the RLN is that the m ore
nerve is safely sequ estered u nd er the cricop haryngeal fas-
it is d issected , the m ore it looks like the correct stru ctu re.
cia to the su p erior vessels themselves, thu s safely separat-
This is based upon the m orphologic appearance and the
ing the nerve from the tissu e to be d ivid ed (Fig. 42.3).
anatom ic cou rse. The nerve can tolerate m anip u lation,
bu t not cu tting. Once cu t, repair of the nerve is of Sympathetic chain
unp roven benefit.
Although it is sep arated from the posterior aspect of the
2. Identify the nerve low in the neck, well below the
thyroid , the sym p athetic chain and stellate ganglion can be
inferior thyroid artery, at the level of the lower pole of
d am aged d u ring thyroid ectom y, p rod u cing a H orner ’s
the thyroid gland, or below (Fig. 42.1). This allow s d is-
synd rom e (ip silateral p tosis, m iosis, and anhid rosis). This
section of the nerve at a site w here it is not tethered by
is p robably d u e to retractor-ind u ced inju ry, as the sym pa-
its attachm ents to the larynx or its relation to the inferior
thetic chain and ganglion itself are out of the operative
thyroid artery. Traction inju ries to the nerve can occu r
field . These inju ries are nearly alw ays tem p orary.
w hen the nerve is m anip ulated near a site of fixation.
3. Keep the nerve in view during the subsequent dissec-
tion of the thyroid away from the larynx. Once the nerve ■ Airway management
is id entified , the d issection can generally proceed from
As the thyroid lies d irectly anterior to the trachea, enlarge-
inferior to superior along the nerve, d ivid ing the inferior
m ent of the thyroid or d irect invasion of the trachea by
thyroid artery branches and preserving the parathyroid
tu m or can cause airw ay com prom ise that can becom e criti-
glands. This allows careful dissection of the tissues w ith
cal d u ring the ind u ction of anesthesia (48–51). Com pres-
minimal manipulation of the RLN .
sion of the trachea can cau se loss of airw ay patency in the
4. Minimize the use of powered dissection posterior to
su p ine p atient u nd er anesthesia. Once the negative
the thyroid. Alth ou gh the electrocau tery and h igh -
intrathoracic p ressu re need ed to lift the thyroid and keep
frequ ency u ltrasonic scalp el are u sefu l tools in d issec-
the trachea p atent is lost, it m ay be d ifficu lt or im possible to
tion, they have som e risk of lateral therm al sp read ,
ventilate the p atient w ith p ositive p ressu re. This can be
w hich can d am age ad jacent tissu es. Carefu l cold d issec-
avoid ed by aw ake intu bation, to m aintain airw ay patency.
tion and hem ostasis w ith ligatu res or clip s w ill avoid
Com pression of the trachea in the neck can narrow the
this risk. This is particu larly im portant at the entry of the
lu m en su bstantially and requ ire p lacem ent of a sm aller
RLN to the larynx, im m ed iately ad jacent to the ligam ent
end otracheal tu be at intu bation. H ow ever, the more d iffi-
of Berry and its vessels.
cu lt m anagem ent issu e can be significant lateral d eviation
The u se of nerve stim u lators and laryngeal m u scle of the trachea. Althou gh these p atients can u su ally be ven-
potential m onitors has recently been investigated as a tool tilated by p ositive p ressu re m ask ventilation, the shift of
FIGURE 42.3. Protection of the Direction of dissection

external branch of the superior
laryngeal nerve. A: After separation Cricothyroid
of the lateral border of the thyroid muscle
gland from the carotid sheath to
Superior thyroid
expose the lateral portion of the artery and vein
upper pole vessels, the medial
aspect of the upper pole is exposed
by bluntly entering the avascular
space between the thyroid gland
and the cricothyroid muscle. This Carotid
space is safe if dissected directly B
artery
posteriorly to the anterior surface of
the spine. B: The dissection is then
Cricothyroid muscle
carried superolaterally between the
surfaces of the thyroid gland and the
cricothyroid muscle (arrow). C: This
maneuver clears the medial aspect
of the superior thyroid vessels, and
4
r '0
traction on the thyroid gland inferi-
he
orly separates the external branch F isc
of the superior laryngeal nerve from HR
these vessels. The vessels can then
A
be safely divided using any tech-
nique, including the high-frequency
ultrasonic dissector (depicted).
Superior branch of external
laryngeal nerve
Superior thyroid
artery and vein
Cricothyroid muscle
Carotid artery
Vibrating
scapel
4
r '0
he
F isc
HR
the larynx can m ake it d ifficu lt or im p ossible to access the are large tu m ors that extend ou t of the u su al confines of
vocal cord s for p lacem ent of an end otracheal tube. Intu ba- the thyroid gland . The thoracic d u ct em p ties into the left
tion over a fiberop tic laryngobronchoscop e can be help fu l internal ju gu lar vein, p osterior to the clavicu lar insertion
in m ost p atients. H ow ever, there are patients w ho cannot of the sternocleid om astoid m u scle. Dam age to the thoracic
be intu bated in sp ite of all attem pts, w ho requ ire tra- d u ct can cau se a large collection of lym p h or chyle in the
cheostom y at the ou tset of the thyroid ectom y, in ord er to op erative bed . This can heal sp ontaneou sly after d rainage
safely p erform the op eration. Anticipation of the d ifficu l- if the leak is sm all; how ever, frequ ently, the leak continu es
ties that m ay be faced , the assem bly of a team expert in air- in sp ite of attem p ts to allow healing by d ecreasing ou tp u t
w ay m anagem ent, and the read iness of an experienced (N PO, total p arenteral nu trition, and octreotid e injec-
su rgeon p rep ared to access the airw ay op eratively is criti- tions). If the leak p ersists for 3 w eeks, then the thoracic
cal to the safe outcom e of these occasionally extrem ely d u ct can be d ivid ed in the left hem ithorax u sing thoraco-
challenging and d angerou s situ ations. scop ic techniqu es. This w ill nearly alw ays allow the leak
to heal.
Tracheal inju ries can occu r, p articu larly d u ring rem oval
■ Injury to other cervical structures of large invasive tu m ors. Most tracheal in ju ries can be
There are a variety of other stru ctu res in the neck that are rep aired p rim arily w ith resorbable su tu re. For d efects
vu lnerable to inju ry d u ring op eration, p articu larly if there 10 m m , it m ay be p referable to p atch the trachea w ith a
p ed icle of the stern ocleid om astoid m u scle, or to p erform need to red ocu m ent and ad ju st thyroid horm one d osing
a sleeve resection of th e affected area. If resected , th e cu t after these changes in other m ed ications.
end s of the trachea are reap p roxim ated w ith absorbable
su tu re. A d rain shou ld be p laced to evacu ate any air that
escap es throu gh the rep air. This is less of an issu e if the
■ PARATHYROID SURGERY
p atien t is extu bated at the com p letion of the op eration , Parathyroid ectom y is p erform ed frequ ently for p rim ary
avoid in g the effects of p ositive p ressu re ven tilation on hyp erp arathyroid ism and less frequ ently for second ary or
the rep air. A tracheostom y is rarely necessary, althou gh if tertiary hyp erp arathyroid ism . The ind ications for inter-
there are other issu es concerning airw ay safety, then vention vary w ith the clinical situ ation. Althou gh som e
p lacem en t of a tem p orary trach eostom y m ay be p refer- recent changes in op erative strategy have m ad e the op era-
able to p rolonged intu bation. tion sim p ler for m any p atients, this p roced u re can still be
Esop hageal inju ries rarely occu r d u ring thyroid ectom y. d ifficu lt and su rgeons u nd ertaking it m u st be skilled at
If the esop hageal lum en is entered , then the op erative recognizing the p athology and correcting it, w hile avoid -
op tions inclu d e p rim ary rep air or closu re of the d istal ing the com p lications of p ersistent hyp erp arathyroid ism
lum en and construction of a cervical esophagostom y. Pri- and hyp op arathyroid ism .
mary rep air is generally preferable, u nless there is exten-
sive tissu e loss or d am age. ■ Indications for operation in patients with
primary hyperparathyroidism
■ Iatrogenic hyperthyroidism or hypothyroidism Patients w ith p rim ary hyperparathyroid ism can be sepa-
After total thyroid ectom y, and as a p art of the therap y for rated into sym p tom atic and asym p tom atic grou ps (61).
m ost th yroid carcin om a, p atients receive thyroid hor- Barring other life-lim iting illness, all p atients w ith sym p to-
m on e rep lacem ent therap y (12). As a chronic m ed ication , m atic hyp erp arathyroid ism shou ld have op erative correc-
thyroid horm one is am ong the m ost w ell-tolerated . It has tion of the d isease. The sym p tom s that can occur inclu d e
a long h alf-life, w hich m akes d aily d osing ad equ ate and fractu res, p articu larly vertebral com p ression fractu res,
w h ich m ean s that p atien ts d o n ot d evelop sym p tom s if renal stones, severe neu rom u scu lar w eakness, easy fatiga-
they m iss or change the tim ing of d oses. The p roblem s bility and loss of stam ina, sleep d istu rbance, d epression,
w ith th yroid h orm on e ad m in istration , h ow ever, are as m em ory loss, and p ancreatitis. All these issues im prove
follow s: (a) its lon g h alf-life allow s ad ju stm ent of d osage w ith correction of hyp erp arathyroid ism . The hypertension
only once p er m onth or so, m aking the titration of the that occurs m ore frequently in the hyp erparathyroid popu-
p rop er d ose a slow p rocess; (b) its n arrow therap eu tic lation p robably stop s w orsening w ith correction of the d is-
w in d ow m eans that sm all ch an ges in d osin g or m ed ica- ease, bu t d oes not reliably im p rove.
tion p rep aration can change the p hysiologic effect; and Patients w ith asym p tom atic d isease can present m ore
(c) it is largely p rotein -bou nd , an d so oth er p rotein - com p lex d ecision-m aking (61–63). Managem ent gu id elines
bou nd d ru gs or changes in the p roteins them selves can for p atients w ith asym p tom atic hyp erp arathyroid ism from
change the effects of a given d ose of the d ru g. Once the N ational Institu tes of H ealth recognize risk factors for
p atien ts u n d erstan d that th e p rocess of titration can take long d u ration of d isease (age), rate of calciu m loss (serum
tim e, they are u su ally accep ting. Trying to sp eed the calciu m and u rine calciu m ), and end -organ effects (serum
p rocess by m akin g m ore frequ ent chan ges often d elays creatinine and bone d ensity) (Table 42.6). The patient’s risk
the id entification of the ap p rop riate d ose by overcorrect- for the operation and concurrent illnesses must be consid -
ing the d ose. ered to d etermine w hether the patient is likely to gain bene-
The narrow therap eu tic w ind ow of thyroid horm one fit from th e p roced u re. These gu id elines w ere d esigned
efficacy is another asp ect that patients shou ld u nd erstand . in an N IH Consensus Conference in 1991 and then revisited
In p articu lar, the effect of changing thyroid horm one and revised in an N IH -sponsored meeting in 2002 (61,63)
prep arations, from one brand to another, or to generic and have been since revisited again (62). The most signifi-
prep arations, m ay change the patient’s resp onse to the cant change w as from Z score for bone d ensity that w as
d ru g. Patients shou ld be encouraged to be consistent abou t u sed in 1991 to T score in 2002. Z score com pares p atient
the p rep aration that they u se or, if a change is u navoid able, bone d ensity to age, gend er, and race-m atched controls,
to recheck their TSH levels a m onth after a change, to d ocu - w hereas T score com p ares p atient bone d ensity to id eal
ment the effect. This has been w ell-d ocum ented in the bone m ass. T score correlates better w ith fractu re risk and so
med ical and lay literatu re, and m ost p harmacists are also is more appropriate in jud ging the patient’s personal risk.
sensitive to this issue (52–60). Once the d ecision to op erate is clear, then the best
A m ore frequ ent p roblem is the ad d ition or su btraction strategy for resolu tion of the hyp erp arathyroid ism can be
of som e other chronic m ed ication, such as oral contracep - consid ered , inclu d ing d ecisions regard ing p reop erative
tive p ills or estrogen rep lacem ent therap y that changes the im aging. Im agin g sh ou ld not be u sed to d eterm ine th e
seru m p rotein bind ing of the thyroid horm one d ose. d iagnosis of hyp erp arathyroid ism , nor the d ecision for
Patients shou ld be inform ed of this p otential effect and the op eration .
Table 4 2 .6 In d ica t ion s for p a r a t hyroid ect om y in localization w ith a gam m a rad iation probe and nuclear
a sym p t om a t ic hyp er p a r a t hyroid ism m ed icine ad m in istration at op eration , thou gh th is has
p roved less u sefu l than w as initially hop ed .
Measurement Guidelines, 1990 Guidelines, 2002 The conventional ap p roach to p arathyroid ectom y has
Serum calcium 1–1.6 mg/dL 1.0 mg/dL been a fu ll neck exp loration w ith id entification of all
(above ULN) p arathyroid gland s and rem oval of the enlarged ones. This
24-Hour urinary 400 mg 400 mg p roven ap p roach has a su ccess rate of 95% to 97%. It relies
calcium on the su rgeon’s ability to recognize the abnorm al gland s
by their size. The p itfalls of the ap p roach are failu re to id en-
Creatinine clearance Reduced by 30% Not recommended
tify all the gland s, leaving an abnorm al gland or gland s in
Serum creatinine Not recommended If abnormal p lace, and the resection of norm al-fu nctioning gland s that
Bone mineral density Zscore Tscore can prod u ce hyp oparathyroid ism .
2.0 (forearm) 2.5 at any site The new er approaches to parathyroid operation improve
Age 50 50 upon the previous approach by helping to id entify the
abnormal gland before operation (giving the surgeon a place
to start the exploration) and by provid ing a physiologic,
rather than anatomic, end point for the operation (letting the
■ Indications for operation in patients with surgeon know w hen to stop). This may theoretically
secondary hyperparathyroidism im p rove the ou tcom e of p arathyroid ectom y; how ever, in
p ractical term s, the op eration w as alread y very safe and
Second ary and tertiary hyperparathyroid ism occur because su ccessfu l. The m ain benefit has been to m ake the easy
of chronic parathyroid stimulation by hypocalcemia, usu- op eration s easier; the m ajority of p atien ts w ith a sin gle
ally in patients w ith chronic renal failure on d ialysis. The ad enom a can have it id entified by p reop erative im aging,
best management of this is to correct the u nd erlying p rob- resected in a focu sed op eration, and avoid fu rther exp lo-
lem , by renal transplant or by d ialysis m anagem ent and ration if the PTH level falls ap p rop riately (67,68). The d if-
vitamin D replacement. These measures can limit the ficu lt op erations, w ith m u ltip le or ectop ic abnorm al
parathyroid abnormality and consequ ent bone d isease in glan d s, are h elp ed by the availability of these m od alities,
most patients, but if the PTH level is chronically 1,000 pg/ bu t can still be qu ite challenging. There are som e p atient
m L, then the n onop erative m easu res are u n likely to situ ations in w hich lim ited neck exp loration for p rim ary
resolve the hyperparathyroidism. However, in patients who hyp erp arathyroid ism is n ot ap p rop riate becau se of a
develop severe bone pain, severe itching, soft-tissue calcifi- high risk of m u ltip le glan d d isease. These are fam ilial
cation, or tissue d amage from microcalcification (calciphy- hyp erp arathyroid ism (in clu d in g th e m u ltip le en d ocrin e
laxis), parathyroidectomy can be beneficial (64–66). Because neop lasia syn d rom es) and hyp erp arath yroid ism d u rin g
of the second ary nature of the hyperparathyroid ism, a full lith iu m u se.
cervical exploration is necessary to identify and manage the The m ost typ ical w ay that these m od alities are incorp o-
disease in all the parathyroid glands. Intraoperative PTH rated is called the m inim ally invasive p arathyroid ectom y
levels may be helpful (65). or concise p arathyroid ectom y (68,69). After the d ecision to
Tertiary hyp erp arathyroid ism occu rs w hen chronically op erate, technetiu m sestam ibi scanning or cervical u ltra-
stim u lated p arathyroid tissu e becom es au tonom ou s and sou nd is u sed to try to id entify the abnorm al gland s. Each
d rives the calciu m to su pernorm al levels. This typ ically of these mod alities is su ccessfu l in 80% to 90% of patients.
occu rs only after renal transp lant has corrected the need for If a su sp iciou s gland is id entified , then the surgeon
d ialysis. Usu ally ju st one of the parathyroid gland s has exp lores that site in the op erating room , often u nd er sed a-
becom e au tonom ou s, and it is not necessary to resect all the tion, and local anesthesia or regional nerve blockad e. If an
gland s. abnorm al gland is id entified , then it is resected , and the
seru m PTH level m easu red 10 m inu tes after excision. If the
■ Current procedure strategies p ostexcision PTH level falls by 50% from the p reexcision
baseline level, then the op eration is com p leted . If no abnor-
Initial Operation m al gland is id entified at the su sp iciou s site, or if the PTH
For patients w ho have no previous history of parathyroid level d oes not fall ad equ ately, then ad d itional exploration
or thyroid op eration, the approach to parathyroid ectom y to id entify all the abnorm al gland s is d one, u su ally d u ring
has changed su bstantially in recent years, d ue to im p rove- the sam e anesthetic; this occu rs in abou t 10% of patients.
ments in the ability to id entify the abnorm al parathyroid The techniqu e for these p atients, as for those w ho have no
gland s preoperatively and the ability to m easu re PTH gland s id entified on p reop erative im aging, is sim ilar to the
intraoperatively for im m ed iate feed back regard ing ad e- conventional fu ll neck exp loration, w ith one d istinction.
qu acy of the resection. Most p arathyroid su rgeons u se Becau se of the available PTH m easu rem ents, the operation
som e com bination of these ad vances in their ap p roach to can be term inated w hen the PTH level d rop s by 50%, even
parathyroid ectom y. Som e also incorporate intraop erative if all the parathyroid gland s have not been id entified .
Reoperation several months. The only treatment necessary is calcium

Reoperation for persistent or recurrent hyperparathy- replacement. If large amounts of calcium are need ed, then
roidism has increased challenges because of the scar from vitamin D can be helpful to aid absorption, as in the treat-
the previous exploration and because there may be specific ment of hypoparathyroidism. The serum PTH level is normal
anatomic reasons (especially ectopic glands outside of the or high, responding appropriately to the hypocalcemia (76).
neck) that caused the initial operation to fail. For these rea- H yp op arathyroid ism can occu r after resection of all
sons, it is imperative for the surgeon to have localization of p arathyroid tissu e, either d u ring an op eration for m ultiple
the abnormal that is as precise as possible, prior to beginning gland p arathyroid d isease or d u ring a reop eration, before
the exploration (68, 70–75). All the information from the pre- w hich som e p arathyroid tissu e m ay have been d am aged or
vious exploration must be reviewed , including the operative resected at the initial p roced u re. This is an u ncomm on
report and pathology report, so that the locations and histocom p lication, p articu larly now that intraop erative PTH
logic nature of the id entified parathyroid glands can be con- m easu rem ent can d ocu m ent the p resence of fu nctional
sid ered . The patient must also have d efinitive imaging that p arathyroid tissu e at the com p letion of the exp loration. If,
correlates w ith the previous operative information. Most at the end of a d ifficu lt or reop erative p arathyroid ectom y,
experienced parathyroid surgeons require tw o concordant the PTH level has d rop p ed to u nm easu rable levels, then
preoperative images of the abnormal gland, before proceed- the best m anagem ent is to au tograft som e of the resected
ing with exploration. The most commonly used initial imag- p arathyroid tissu e, follow ing the sam e gu id elines noted
ing techniques are technetium sestamibi nuclear imaging earlier (Fig. 42.2). Abnorm al p arathyroid tissu e should not
and cervical ultrasound . If these both identify w hat appears be grafted into the neck, how ever, and so au tografting into
to be the same gland , then no further imaging is need ed . If the nond om inant forearm m ay be m ore ap p rop riate.
they are not, then further stud ies proceed . Usually, noninva-
sive imaging mod alities are utilized first (CT scan of the neck ■ Nerve injury
and chest and MRI scan) and invasive imaging only if
needed (selective venous sampling for PTH and arteriogra- The sam e nerves that are at risk d uring thyroid ectom y are
phy). The sequence of these stud ies depend s upon the indi- at risk d u ring p arathyroid ectomy becau se of the proximity
vid ual patient findings and local experience and expertise of the d issection. H ow ever, becau se there is rarely a need to
w ith these stud ies. Our preferences are led by our experi- d ivid e the u pper pole thyroid vessels d uring parathyroid ec-
ence w ith CT scan and selective venous sampling. tom y, the external branch of the su perior laryngeal nerve is
The reop eration for hyp erp arathyroid ism is cond u cted at su bstantially less risk. The RLN can be qu ite close to the
in a fashion sim ilar to the initial proced u re. The su sp iciou s p arathyroid gland s and in fact is sometimes enveloped in a
site is exp lored , and abnorm al tissu e resected . The intraop - groove in an enlarged upper parathyroid gland that extend s
erative PTH level is u sed to d eterm ine w hether that has inferiorly along the esophagus and nerve. The main princi-
resolved the hyp erp arathyroid ism and w hether any fu r- p le that is u sed to protect the RLN d u ring parathyroid ec-
ther exp loration, or parathyroid au tograft, is necessary tom y is to avoid d ivid ing any stru ctures other than the
(70,71). The sam e criteria are used for successfu l d rop in the mid d le thyroid vein, until the parathyroid gland is com-
intraoperative PTH level. p letely mobilized . Once the gland is attached only at one
site by artery and vein, then the nerve cannot be involved ,
and it is safe to d ivid e the vessels. The RLN is often id enti-
■ Potential complications of parathyroidectomy fied d u ring the course of the parathyroid d issection. If there
Any of the com plications that can occu r in thyroid opera- is any question regard ing the location of the nerve, the same
tions, can occu r in parathyroid operations, save the p ro- technique of nerve id entification d escribed earlier is u sed to
d u ction of hyp othyroid ism . In particular, the comp lications p rotect the nerve from inju ry (Fig. 42.1).
of n eck h em atom a, n erve in ju ries, an d h yp op arath y-
roid ism occu r for sim ilar reasons an d are m an aged in ■ Persistent or recurrent hyperparathyroidism
sim ilar w ays. Persistent hyp erp arathyroid ism is u niqu e
to p arathyroid ectom y. Persistent hyperparathyroid ism is the appearance of
hyp ercalcem ia and elevated PTH levels w ithin 6 m onths
after p arathyroid exp loration. Most often, this occu rs w hen
■ Hypoparathyroidism the parathyroid ad enom a is not id entified at exp loration,
Hypocalcemia occurs after parathyroidectomy because of or w hen m u ltigland u lar d isease is not recognized . Recur-
either bone remineralization or hypoparathyroidism. If rent hyperparathyroid ism is the reappearance of hypercal-
hyperparathyroidism has been corrected in a patient with cemia and elevated PTH levels 6 months after exploration.
significant bone disease, then the bone remineralization This usually occurs because of unrecognized mild multiglan-
process can remove substantial amounts of calcium from the d ular disease, when there is an underlying stimulus for the
blood and cause hypocalcemia. This symptomatic process d evelop m ent of m ore abnorm al p arathyroid gland s (e.g.,
usually resolves within 2–4 weeks after parathyroidectomy MEN -1), or if a p arath yroid ad en om a is in com p letely
but, in patients w ith very severe bone disease, can go on for resected or fractu red (77). These p roblem s occur in 2% to
4% of p atients after operation in experienced hand s. Prop er blood su p p ly from the laryngeal system (Fig. 42.4). Thu s,
perform ance of the neck exp loration and u se of the intraop - all the tissu es attached to the larynx rem ain attached at the
erative PTH assay should m inim ize the occu rrence of this end of the m obilization so that the parathyroid gland s and
problem (70,71). their blood su p p ly are not sep arated and d rop p ed into an
To m axim ize the therap eu tic valu e and m inim ize the “acqu ired ectop ic” p osition. Once the tissu es have been
operative risks of p arathyroid ectom y, the m ost im portant m obilized , then the norm al sites for p arathyroid gland s can
factor is thorou gh and p recise d issection techniqu e. The be easily exp lored . Most m issed p arathyroid ad enom as
operation, w hether p erform ed as a focused exploration that cau se p ersistent hyp erp arathyroid ism are in norm al
beginning at one site or perform ed as a full parathyroid anatom ic sites and w ere m issed at initial op eration.
exploration, m u st proceed in an organized w ay. The If no p arath yroid glan d is id en tified in a corresp on-
parathyroid gland s are exposed by d issecting the su p erfi- d in g n orm al site, th en know led ge of the ectop ic sites
cial structures of the neck (from the strap m uscles out) w h ere p arath yroid glan d s can be gu id es fu rth er exp lo-
aw ay from the u nd erlying structures that d erive their ration (Fig. 42.5). While ectop ic p arathyroid ad enom as
FIGURE 42.4. Exposure and identifica-

tion of the parathyroid glands in their normal
anatomic positions. A: After making sub- Platysma muscle
platysmal flaps and separating the strap
muscles in the midline, the elevation of the Anterior Strap muscles
strap muscle proceeds immediately along jugular vein
the strap muscles and the carotid sheath Left lobe of thyroid
Strap muscles
directly posteriorly to the longus coli mus-
Sternocleidomastoid
cle. Only after the anterior surface of the Trachea muscle
longus coli muscle has been exposed
medial to the carotid sheath along the length Common Esophagus
of the thyroid gland, is the dissection turned carotid
medially. This plane leaves all of the tissues artery
likely to contain the parathyroid glands Longus coli muscle
Internal
attached to the larynx. B: The thyroid gland is jugular vein
rolled anteriorly, rotating the larynx and upper Scalene muscles:
trachea to bring the tracheoesophageal tis- Anterior
sues into view. The middle thyroid vein, if it Medial
is placed on tension by this maneuver, is Posterior
divided.
Sternocleidomastoid
Trachea muscle
Recurrent
laryngeal nerve
Spinal Esophagus with

body intraluminal tube
Spinal
cord
B
Cricothyroid
muscle
Cricothyroid
Upper para- muscle
thyroid gland
Inferior
thyroid artery
Recurrent
laryngeal
nerve
Inferior para-
Inferior thyroid gland
thyroid artery R
H
Fi Inferior
sc
he
r '0 4 thyroid artery
Recurrent
laryngeal Thymus
4
0
er' nerve in TE tissue
h
isc
HR
F groove
C D
FIGURE 42.4. (Continued) C: The upper parathyroid gland is most often identified immediately adjacent to the thyroid gland, posterior
to the recurrent laryngeal nerve (RLN), and superior to the inferior thyroid artery. However, when enlarged, the gland often grows inferi-
orly, with the bulk lying deep to, and extending inferior to, the inferior thyroid artery, still posterior to the RLN. The blood supply remains
from the upper branches of the inferior thyroid artery, however, and can be identified in the normal position. D: The lower pole of the thy-
roid gland is retracted superiorly to identify the lower parathyroid gland. This is most often immediately adjacent to the thyroid gland,
though it can “slide down” within the sheath of the thymus and often resides there. To uncover the parathyroid in this area, the sheath
overlying the thymus is opened, but the attachments to the thyroid gland are not divided as they provide important traction superiorly.
FIGURE 42.5. Identification of the parathyroid

glands in ectopic sites. A: The upper parathyroid
glands usually remain close to the thyroid, how-
ever, if the gland is not present there, then it is most
Sternum likely posterior to the recurrent laryngeal nerve
Thyroid gland along the esophagus or pharynx (shaded area).
Thymus
B: The lower parathyroid gland is usually near
Thyroid cartilage the lower pole of the thyroid gland; however, it
Innominate Cricothyroid muscle can slide down into the anterior mediastinum
vein and artery within the thymus (shaded area). More rarely, the
Trachea lower parathyroid gland can be in the upper neck
Recurrent
along the carotid artery, often with a bit of resid-
laryngeal nerve Area of ectopic ual thymus attached there as well.
Esophagus upper parathyroid
glands
Sternum
Thymus Thyroid gland
Area of ectopic Thyroid cartilage
lower parathyroid Cricothyroid muscle
glands
Trachea
Innominate
vein and artery Esophagus
Recurrent
laryngeal nerve
B
are u nu su al, they occur frequently enough that no surgeon has often been left u n d issected , th u s leaving th e p osteri-
should undertake this operation without complete familiar- orly p laced gland u nid entified at th e initial attem p t. This
ity with this anatomy. If no abnormal parathyroid tissue is avoid s the ted iou s and som etim es blood y d issection of
found after full neck exploration and after exploration of all th e strap m u scles from the an terior su rface of th e thyroid
cervically accessible ectopic sites, then most parathyroid sur- gland .
geons w ould close the w ound, terminate the operation, and
re-evaluate the patient postoperatively. This should include
reconfirmation of the diagnosis and imaging to try to identify
■ SUMMARY
the abnormal gland. Most surgeons w ould not perform a In conclu sion, op erations for d iseases of the thyroid and
trans-sternal med iastinal exploration at the initial operation p arathyroid gland s are qu ite com m on. Most of the com -
w ithout localizing studies that indicated a gland there. p lications of these p roced u res are technical in natu re, and
Op erative strategy at reop eration shou ld inclu d e con - the risk in these p roced u res can be m inim ized by p rop er
sid eration of alternative anatom ic ap p roaches that m ight u nd erstand ing of the ind ications for op eration, the
avoid op erating throu gh p reviou s scar. The m ost com - anatom y and p athology of the area, and the p rop er d is-
m on altern ative ap p roach is m ost u sefu l for a p osteriorly section ap p roach. The m anagem ent of the com p lications
p laced (u su ally u p p er) p arathyroid ad enom a (Fig. 42.6). d ep end s u p on the severity and tem p oral natu re of the
This lateral ap p roach takes the op eration throu gh fresh com p lication. For m any tem p orary issu es, reassu rance
tissu e lateral to the strap m u scles, along the anterior bor- alone and exp lanation of the natu ral history of the recov-
d er of the sternocleid om astoid m u scle, and only then to ery is all that is necessary. The p erm anent, life-altering
the p reviou sly op erated area m ed ial to the carotid sheath. natu re of som e of the com p lications m akes it m and atory,
This sheath is qu ite d u rable and tolerates d issection eas- as w ith all invasive p roced u res, that the ind ications for
ily, even in reop eration. In ad d ition, this area p osteriorly the intervention be very clear.
Strap muscles
Sternocleidomastoid
muscles
Trachea Sternocleidomastoid
Thyroid gland muscle
Esophagus Carotid artery
A Previous Internal jugular vein
incision scar Abnormal parathyroid
Intervertebral
disk
Strap
muscles
B
4
er '0
h
HR Fisc
Sternocleidomastoid
muscle
FIGURE 42.6. The lateral approach to the tracheoesophageal groove. For patients with previous neck explorations, who have a
posteriorly placed parathyroid gland, a lateral approach can avoid some treacherous dissection. A: The neck is entered usually
through the old incision, or a new more laterally placed incision. B: A fresh plane is entered between the lateral border of the strap
muscles and the medial border of the sternocleidomastoid muscle. The thyroid and strap muscles are then rolled anteriorly as a unit,
exposing the esophagus. This is the area where upper parathyroid adenomas are often missed, and dissection in these planes
avoids the area of the previous dissection of the strap muscles from the thyroid surface and the thyroid from the recurrent laryngeal
nerve.
■ REFERENCES 26. Bu rkey SH , van H eerd en JA, Thom p son GB, et al. Reexp loration for
sym p tom atic hem atom as after cervical exp loration. Surgery 2001;130:
1. Schneid er AB, Ron E, Lu bin J, et al. Dose–resp onse relationship s for 914–920.
rad iation-ind uced thyroid cancer and thyroid nod u les: evid ence for 27. Adler JT, Sippel RS, Schaefer S, et al. Preserving function and quality of
the p rolonged effects of rad iation on the thyroid . J Clin Endocrinol life after thyroid and parathyroid surgery. Lancet Oncol 2008;9:1069–1075.
Metab 1993;77:362–369. 28. Leyre P, Desu rm ont T, Lacoste L, et al. Does the risk of com p ressive
2. Antonelli A, Silvano G, Bianchi F, et al. Risk of thyroid nod u les in sub- hem atom a after thyroid ectom y au thorize 1-d ay su rgery? Langenbecks
jects occu p ationally exp osed to rad iation: a cross sectional stu d y. Occup Arch Surg 2008;393:733–737.
Environ Med 1995;52:500–504. 29. Rosenbau m MA, H arid as M, McH enry CR. Life-threatening neck
3. William s D. Rad iation carcinogenesis: lessons from Chernobyl. Onco- hem atom a com p licating thyroid and p arathyroid su rgery. Am J Surg
gene 2008;27(Su pp l 2):S9–S18. 2008;195:339–343; d iscussion 343.
4. Kouvaraki MA, Shap iro SE, Fornage BD, et al. Role of p reop erative 30. H ard ing J, Sebag F, Sierra M, et al. Thyroid su rgery: p ostop erative
u ltrasonograp hy in the su rgical m anagem ent of p atients w ith thyroid hem atom a—p revention and treatm ent. Langenbecks Arch Surg 2006;391:
cancer. Surgery 2003;134:946–954; d iscu ssion 954–945. 169–173.
5. Ito M, Yam ashita S, Ashizaw a K, et al. Child hood thyroid d isease 31. Farrar WB, Cooperm an M, Jam es AG. Su rgical m anagem ent of papil-
around Chernobyl evalu ated u ltrasou nd exam ination and fine need le lary and follicular carcinom a of the thyroid . Ann Surg 1980;192:701–704.
aspiration cytology. Thyroid 1995;5:365–368. 32. Thom p son N W, N ishiyam a RH , H arness JK. Thyroid carcinom a: cu r-
6. Coop er DS, Doherty GM, H au gen BR, et al. Revised Am erican Thy- rent controversies. Curr Probl Surg 1978;15:1–67.
roid Association m anagem ent gu id elines for p atients w ith thyroid 33. Schrod er DM, Cham bou s A, France CJ. Op erative strategy for thyroid
nod ules and differentiated thyroid cancer [see comment]. Thyroid 2009;19: cancer, is total thyroid ectom y w orth the p rice? Cancer 1986;58:2320.
1167–1214. 34. Clark OH , Levin K, Zeng QH , et al. Thyroid cancer: the case for total
7. Jones AJ, Aitm an TJ, Ed m ond s CJ, et al. Com p arison of fine need le thyroid ectom y. Eur J Cancer Clin Oncol 1988;24:305–313.
aspiration cytology, rad ioisotop ic and u ltrasou nd scanning in the m an- 35. Ley PB, Roberts JW, Sym m ond s RE Jr, et al. Safety and efficacy of total
agem ent of thyroid nod u les. Postgrad Med J 1990;66:914–917. thyroid ectom y for d ifferentiated thyroid carcinom a: a 20-year review.
8. Belfiore A, La Rosa GL, La Porta GA, et al. Cancer risk in patients w ith Am Surg 1993;59:110–114.
cold thyroid nod u les: relevance of iod ine intake, sex, age, and m u ltin- 36. Tartaglia F, Sgueglia M, Mu haya A, et al. Com p lications in total thy-
od u larity. Am J Med 1992;93:363–369. roid ectom y: ou r exp erience and a nu m ber of consid erations. Chir Ital
9. Layfield LJ, Mohrm ann RL, Kop ald KH , et al. Use of asp iration cytol- 2003;55:499–510.
ogy and frozen section exam ination for m anagem ent of benign and 37. Rosato L, Avenia N , Bernante P, et al. Com p lications of thyroid su rgery:
m alignant thyroid nod u les. Cancer 1991;68:130–134. analysis of a m ulticentric stu d y on 14,934 p atients op erated on in Italy
10. Gharib H . Fine-need le asp iration biop sy of thyroid nod u les: ad van- over 5 years. World J Surg 2004;28:271–276.
tages, lim itations, and effect. Mayo Clin Proc 1994;69:44–49. 38. Ru bin MR, Dem p ster DW, Zhou H , et al. Dynam ic and stru ctu ral p rop -
11. Ud elsm an R, Westra WH , Donovan PI, et al. Rand om ized prosp ective erties of the skeleton in hyp op arathyroid ism . J Bone Miner Res 2008;23:
evaluation of frozen-section analysis for follicular neoplasm s of the 2018–2024.
thyroid . Ann Surg 2001;233:716–722. 39. Win er KK, Ko CW, Reyn old s JC, et al. Long-term treatm en t of
12. Mazzaferri EL. An overview of the m anagem ent of p ap illary and follic- hypoparathyroidism: a rand omized controlled study comparing parathy-
u lar thyroid carcinom a. Thyroid 1999;9:421–427. roid hormone-(1–34) versus calcitriol and calcium. J Clin Endocrinol Metab
13. H ay ID, Grant CS, Bergstralh EJ, et al. Unilateral total lobectom y: is it 2003;88:4214–4220.
sufficient su rgical treatm ent for patients w ith AMES low -risk papillary 40. Winer KK, Sinaii N , Peterson D, et al. Effects of once versu s tw ice-d aily
thyroid carcinom a? Surgery 1998;124:958–964; d iscu ssion 964–956. parathyroid horm one 1–34 therap y in child ren w ith hyp op arathy-
14. Chen H , N icol TL, Zeiger MA, et al. H u rthle cell neop lasm s of the thyroid ism . J Clin Endocrinol Metab 2008;93:3389–3395.
roid : are there factors pred ictive of m alignancy? Ann Surg 1998;227: 41. Olson JA Jr, DeBened etti MK, Bau m ann DS, et al. Parathyroid au to-
542–546. transplantation d u ring thyroid ectom y. Resu lts of long-term follow -u p
15. Hay ID, Bergstralh EJ, Goellner JR, et al. Predicting outcome in papillary [see com m ent]. Ann Surg 1996;223:472–478; d iscu ssion 478–480.
thyroid carcinoma: d evelopment of a reliable prognostic scoring system 42. Rea JL, Khan A. Clinical evoked electrom yograp hy for recu rrent laryn-
in a cohort of 1779 patients surgically treated at one institution during geal nerve p reservation: u se of an end otracheal tu be electrod e and a
1940 through 1989. Surgery 1993;114:1050–1057; discussion 1057–1058. postcricoid surface electrod e. Laryngoscope 1998;108:1418–1420.
16. H ay ID, Thom pson GB, Grant CS, et al. Pap illary thyroid carcinom a 43. Otto RA, Cochran CS. Sensitivity and sp ecificity of intraop erative
m anaged at the Mayo Clinic d u ring six d ecad es (1940–1999): tem p oral recurrent laryngeal nerve stim u lation in pred icting postoperative
trend s in initial therap y and long-term ou tcom e in 2444 consecu tively nerve paralysis. Ann Otol Rhinol Laryngol 2002;111:1005–1007.
treated p atients. World J Surg 2002;26:879–885. 44. Dralle H , Seku lla C, Lorenz K, et al. Intraop erative m onitoring of the
17. Yim JH , Doherty GM. Pap illary thyroid cancer. Curr Treat Options Oncol recu rrent laryngeal nerve in thyroid su rgery. World J Surg 2008;32:
2000;1:329–338. 1358–1366.
18. Bilim oria KY, Bentrem DJ, Ko CY, et al. Extent of su rgery affects su r- 45. Dralle H , Seku lla C, H aerting J, et al. Risk factors of p aralysis and fu nc-
vival for pap illary thyroid cancer [see com m ent]. Ann Surg 2007;246: tional ou tcom e after recu rrent laryngeal nerve m onitoring in thyroid
375–381; d iscussion 381–374. surgery. Surgery 2004;136:1310–1322.
19. McIver B, H ay ID, Giu ffrid a DF, et al. Anap lastic thyroid carcinom a: a 46. Thom u sch O, Seku lla C, Machens A, et al. Valid ity of intra-op erative
50-year exp erience at a single institu tion. Surgery 2001;130:1028–1034. neu rom onitoring signals in thyroid su rgery. Langenbecks Arch Surg
20. Sw eeney PJ, H araf DJ, Recant W, et al. Anap lastic carcinom a of the thy- 2004;389:499–503.
roid . Ann Oncol 1996;7:739–744. 47. Stojad inovic A, Shaha AR, Orlikoff RF, et al. Prosp ective fu nctional
21. Kobayashi T, Asakaw a H , Um eshita K, et al. Treatm ent of 37 p atients voice assessm ent in patients u nd ergoing thyroid su rgery. Ann Surg
w ith anaplastic carcinom a of the thyroid . Head Neck 1996;18:36–41. 2002;236:823–832 [see com m ent].
22. Shim izu K, Ku m ita S, Kitam u ra Y, et al. Trial of au totransp lantation of 48. Kitam u ra Y, Shim izu K, N agaham a M, et al. Im m ed iate cau ses of d eath
cryop reserved thyroid tissu e for postoperative hypothyroid ism in in thyroid carcinom a: clinicop athological analysis of 161 fatal cases. J
p atients w ith Graves’ d isease [see com m ent]. J Am Coll Surg 2002;194: Clin Endocrinol Metab 1999;84:4043–4049.
14–22. 49. Ru d ow M, H ill AB, Thom p son N W, et al. H eliu m –oxygen m ixtu res in
23. Thomusch O, Machens A, Sekulla C, et al. Multivariate analysis of risk airw ay obstru ction d u e to thyroid carcinom a. Can Anaesth Soc J 1986;33:
factors for postoperative complications in benign goiter surgery: prospec- 498–501.
tive multicenter study in Germany. World J Surg 2000;24:1335–1341. 50. Allo MD, Thom p son N W. Rationale for the op erative m anagem ent of
24. Cobin RH . Thyroid carcinom a and Graves’ d isease. Endocr Pract 2000; substernal goiters. Surgery 1983;94:969–977.
6:264–267. 51. Sip p el RS, Gau ger PG, Angelos P, et al. Palliative thyroid ectom y for
25. Thom u sch O, Machens A, Seku lla C, et al. The im p act of su rgical tech- m alignant lym p hom a of the thyroid . Ann Surg Oncol 2002;9:907–911.
niqu e on postoperative hypoparathyroid ism in bilateral thyroid su r- 52. Mikosch P, Oberm ayer-Pietsch B, Jost R, et al. Bone m etabolism in
gery: a m u ltivariate analysis of 5846 consecu tive p atients. Surgery 2003; patients w ith d ifferentiated thyroid carcinom a receiving su ppressive
133:180–185. levothyroxine treatm ent. Thyroid 2003;13:347–356.
53. Saw ka AM, Gerstein H C, Marriott MJ, et al. Does a com bination regi- 65. H ibi Y, Tom inaga Y, Sato T, et al. Reop eration for renal hyp erp arathy-
m en of thyroxine (T4) and 3,5,3’-triiod othyronine im p rove d epressive roid ism . World J Surg 2002;26:1301–1307.
sym ptom s better than T4 alone in patients w ith hypothyroid ism ? 66. Rothm u nd M, Wagner PK, Schark C. Su btotal p arathyroid ectom y ver-
Resu lts of a d ou ble-blind , rand om ized , controlled trial. J Clin Endocrinol su s total parathyroid ectom y and au totransp lantation in second ary
Metab 2003;88:4551–4555. hyp erparathyroid ism : a rand om ized trial. World J Surg 1991;15:
54. Walsh JP, Shiels L, Lim EM, et al. Com bined thyroxine/ liothyronine 745–750.
treatm ent d oes not im p rove w ell-being, qu ality of life, or cognitive 67. Ud elsm an R, Pasieka JL, Stu rgeon C, et al. Su rgery for asym p tom atic
function com pared to thyroxine alone: a rand om ized controlled trial in p rim ary hyp erparathyroid ism : proceed ings of the third international
p atients w ith p rim ary hyp othyroid ism [see com m ent]. J Clin Endocrinol w orkshop. J Clin Endocrinol Metab 2009;94:366–372.
Metab 2003;88:4543–4550. 68. Johnson LR, Doherty G, Lairm ore T, et al. Evalu ation of the p erform -
55. Walsh JP. Dissatisfaction w ith thyroxine therap y—cou ld the p atients be ance and clinical im pact of a rapid intraoperative parathyroid horm one
right? Curr Opin Pharmacol 2002;2:717–722. assay in conju nction w ith preoperative im aging and concise p arathy-
56. Saravanan P, Chau WF, Roberts N , et al. Psychological w ell-being in roid ectom y. Clin Chem 2001;47:919–925.
patients on ‘ad equate’ d oses of L-thyroxine: results of a large, controlled 69. Carling T, Ud elsm an R. Focu sed ap p roach to p arathyroid ectom y. World
com m unity-based questionnaire stud y [see com m ent]. Clin Endocrinol J Surg 2008;32:1512–1517.
2002;57:577–585. 70. Wang TS, Ud elsm an R. Rem ed ial su rgery for p rim ary hyp erp arathy-
57. Woeber KA. Levothyroxine therap y and seru m free thyroxine and free roid ism . Adv Surg 2007;41:1–15.
triiod othyronine concentrations. J Endocrinol Invest 2002;25:106–109. 71. Ud elsm an R, Donovan PI. Rem ed ial p arathyroid su rgery: changing
58. Wiersinga WM. Thyroid horm one rep lacem ent therap y. Horm Res trend s in 130 consecu tive cases [see com m ent]. Ann Surg 2006;244:
2001;56:74–81. 471–479.
59. Fischm an J. Rep orts of thyroid d ru g’s d em ise w ere exaggerated . US 72. Wells SA Jr, Debened etti MK, Doherty GM. Recu rrent or p ersistent
News World Rep 2001;131:57. hyp erp arathyroid ism . J Bone Miner Res 2002;17:N 158–N 162.
60. Bell DS, Ovalle F. Use of soy p rotein su p p lem ent and resu ltant need for 73. Kald BA, Molleru p CL. Risk factors for severe p ostop erative hyp ocal-
increased d ose of levothyroxine. Endocr Pract 2001;7:193–194. caem ia after operations for p rim ary hyp erp arathyroid ism . Eur J Surg
61. Bilezikian JP, Potts JT Jr, Fu leihan Gel H , et al. Su m m ary statem ent 2002;168:552–556.
from a w orkshop on asym ptom atic prim ary hyp erparathyroid ism : a 74. H asse C, Sitter H , Bru ne M, et al. Qu ality of life and p atient satisfaction
p ersp ective for the 21st centu ry. J Clin Endocrinol Metab 2002;87: after reoperation for p rim ary hyperparathyroid ism : analysis of long-
5353–5361. term resu lts. World J Surg 2002;26:1029–1036.
62. Bilezikian JP, Khan AA, Potts JT Jr; Third International Workshop on 75. Kivlen MH , Bartlett DL, Libu tti SK, et al. Reop eration for hyp er-
the Managem ent of Asym p tom atic Prim ary H yp ertension. Gu id elines p arathyroid ism in m u ltip le end ocrine neop lasia typ e 1. Surgery 2001;
for the m anagem ent of asym ptom atic prim ary hyperparathyroid ism : 130:991–998.
su m m ary statem ent from the third international w orkshop . J Clin 76. Mand al AK, Ud elsm an R. Second ary hyp erp arathyroid ism is an
Endocrinol Metab 2009;94:335–339. expected consequ ence of parathyroid ectom y for prim ary hyper-
63. N IH conference. Diagnosis and m anagem ent of asym p tom atic prim ary p arathyroid ism : a prospective stu d y. Surgery 1998;124:1021–1026; d is-
hyperp arathyroid ism : consensus d evelop m ent conference statem ent. cu ssion 1026–1027.
Ann Intern Med 1991;114:593–597. 77. Fraker DL, Travis WD, Merend ino JJJ, et al. Locally recu rrent p arathy-
64. Rothm u nd M, Wagner P. Reop erations for p ersistent and recu rrent sec- roid neop lasm s as a cau se for recurrent and persistent p rim ary hyper-
ond ary hyperparathyroid ism . Ann Surg 1988;207:310. p arathyroid ism . Ann Surg 1991;213:58–65.
CHAPTER
43
Complications in Endocrine
Pancreatic Surgery
Cortney Youens Lee and Terry C. Lairmore
End ocrine p ancreatic neop lasm s p resent u niqu e d ilem - tu m ors w ith significant m alignant p otential, shou ld also
m as in d iagnosis, op tim al tim ing and extent of op erative be resected w ith or w ithou t the p resence of a sp ecific syn-
intervention, and m anagem ent of the p ostop erative com - d rom e of horm one excess. Althou gh end ocrine p ancreatic
p lications that occu r w ith increased frequ ency in this neop lasm s are generally thou ght to p u rsu e an ind olent
select grou p of p atients. N eu roend ocrine tu m ors (N ETs) clinical cou rse in m ost p atients, regional lym p h nod e
of the p ancreas and d u od enu m m ay occu r as sp orad ic m etastases and hep atic and d istant m etastases can occu r
entities or in association w ith one of several hered itary and be life-lim iting d u e to p rogression of the tu m oral
end ocrine neop lasia synd rom es. Sp orad ic N ETs of the p rocess. In a recent series of p atients w ith N ETs in the set-
p ancreas occu r infrequ ently, w ith an estim ated incid ence ting of m u ltip le end ocrine neop lasia typ e 1 (MEN 1)
of 1 p er 100,000. These neop lasm s are m ost com m only u nd ergoing op eration based on trad itional ind ications
d iagnosed in the fou rth or fifth d ecad e of life w ith a slight (horm onally active tu m or and tu m ors 1 cm and p er-
fem ale p rep ond erance. Du od enop ancreatic N ETs com - ceived to carry significant m alignant p otential), ap p roxi-
m only p resent either w ith signs and sym p tom s relating to m ately one-third of p atients had lym p h nod e or d istant
local grow th of the tu m or m ass or w ith a sp ecific syn- m etastases at the tim e of intervention (1). In one of the
d rom e of horm one excess. Patients w ho are m em bers of a largest series (2) of p atients u nd ergoing p ancreaticod u o-
know n kind red w ith one of the hered itary end ocrine neo- d enectom y for p ancreatic or p eriam p u llary N ETs (sp o-
p lasia synd rom es m ay be d iagnosed early as a resu lt of rad ic and fam ilial), the actu arial su rvival rates at 2, 5, and
p rosp ective fam ily screening, w hile sp orad ic end ocrine 7 years w ere 81%, 73%, and 65%, resp ectively. A m ore
p ancreatic neop lasm s tend to p resent late ow ing to their recent series of 324 p atients w ith end ocrine p ancreatic
infrequ ent occu rrence and u nu su al constellation of p retu m ors rep orted 5- and 10-year su rvival rates of 64% and
senting and clinical find ings. 44%, resp ectively (3). Clearly, end ocrine p ancreatic tu m ors
Op erative in tervention for p ancreatic N ETs is gener- can be aggressive and resu lt in m ortality in a su bset of
ally in d icated for p atien ts w ith fu nction al tu m ors an d for p atients.
tu m ors w ith significant m alignant p otential. Patients Pancreatic N ETs that are associated w ith one of the
w ith inap p rop riate horm one oversecretion m ay d evelop hered itary end ocrine neop lasia synd rom es p resent u niqu e
life-threatening fasting hyp oglycem ia (insu linom a); d iagnostic and therap eu tic challenges (1,4). H ered itary
severe com p lications of p ep tic u lceration, inclu d ing cancer synd rom es are characterized by a d iffu se p reneo-
bleed ing, p erforation, obstru ction, and / or com p lications p lastic hyp erp lasia that p reced es the d evelop m ent of
from gastroesop hageal reflu x (gastrinom a); or d ebilitat- d iscrete tu m or foci w ithin the involved tissu e, the d evelop-
ing secretory d iarrhea w ith associated flu id and elec- m ent of m u ltip le tu m ors w ithin a target tissue, and the
trolyte losses (vasoactive intestinal p ep tid e tu m ors p otential for d evelop m ent of tu m ors in m ore than one tar-
[VIPom as] and carcinoid tu m ors). Rare horm onally active get tissu e. Fu rtherm ore, in the setting of a fam ilial cancer
tu m ors su ch as glu cagonom as and som atostatinom as p ro- synd rom e, affected p atients d evelop tu mors at a m uch ear-
d u ce u nu su al bu t clinically significant synd rom es, inclu d - lier age than p atients w ith correspond ing sporad ic tu m ors.
ing hyp oam inoacid em ia, d iabetes m ellitu s, d eep vein For exam p le, in keep ing w ith the tw o-hit m od el for a
throm bosis (DVT)/ p u lm onary em bolism , and cu taneou s tu m or su p p ressor gene (5), p atients w ith MEN 1 inherit
necrolytic migratory erythema (glucagonomas), or cachexia, one m u tation in the germ line and requ ire only one ad d i-
steatorrhea, and cholelithiasis (som atostatinom as). Pan- tional genetic event to inactivate the rem aining w ild -typ e
creatic N ETs that are know n to be m alignant, or those allele and resu lt in tu m or form ation. The resu lt is a p ropen-
sity to d evelop m u ltip le end ocrine tu m ors at a you ng age,
Cortney Youens Lee, Terry C. Lairmore: Texas A & M w hen p atients are otherw ise healthy and active. Although
University System H ealth Sciences Center, College of Medicine, as a grou p N ETs tend to be benign or follow an ind olent
Temp le, TX 76508. cou rse, a su bset of these tu m ors m ay m etastasize early to
567
A B
FIGURE 43.1. Benign insulinoma resection. A: A small insulinoma (placed in a retrieval device) after laparoscopic enucleation from
surrounding pancreatic parenchyma. Most insulinomas have no invasion of the surrounding pancreas, and so gross enucleation is cura-
tive therapy. B: Multifocal pancreatic islet cell tumors from a distal pancreatectomy specimen in a multiple endocrine neoplasia type 1
patient. In some situations, there may be less risk of operative complications associated with limited pancreatic resection than there is
with enucleation. In this situation, a low-morbidity resection was preferable.
regional lym p h nod es, liver, or d istant sites w ith resu ltant biliary d u cts; and the significant clinical and financial costs
cancer-related m ortality. The optim al su rgical m anagem ent of failing to accu rately localize and resect fu nctional
of these tu m ors is com p licated by a relative lack of sensi- tu m ors or to p revent m alignant p rogression w ith ad equ ate
tive and sp ecific tu m or m arkers for their early d etection, p ancreatic resection.
d ifficu lty in accu rately localizing sm all tum ors by noninva-
sive preop erative imaging tests, and u ncertainty abou t the
malignant potential or expected natural history of sm all,
■ APPROACH TO RESECTION OF ENDOCRINE
PANCREATIC TUMORS
apparently benign, tu m ors (6).
Mention of the controversies su rrou nd ing the su rgical The op erative ap proach to excision of p ancreatic and d uo-
m anagem ent of p ancreatic N ETs is very p ertinent to any d enal N ETs inclu d es com p lete exp osu re of the p ancreas by
d iscu ssion of the com p lications of p ancreatic end ocrine entering the lesser sac, p erform ing an extend ed Kocher
su rgery becau se the p otential risks shou ld greatly influ - m aneu ver (m obilization and m ed ial rotation of the d u od e-
ence d ecisions regard ing the tim ing and extent of the op er- nu m and head of the p ancreas from the retrop eritoneu m ),
ative p roced u re. Becau se of the high p robability that a incision of the retrop eritoneu m at the inferior bord er of the
sm all, solitary, grossly encap su lated N ET of the p ancreas p ancreas, and m ed ial rotation of the sp leen and tail of the
w ill be benign, enu cleation is u su ally ap p rop riate (1,7–12). p ancreas. These maneu vers allow thorou gh insp ection and
Localized resection p reserves p ancreatic end ocrine and p alp ation of the entire p ancreatic p arenchym a. Becau se
exocrine fu nction and p revents the need for d ivision of the 60% to 70% of gastrinom as are located in the su bm ucosa of
m ajor p ancreatic d u ct or the need for constru ction of a the d u od enal w all, a longitu d inal d u od enotom y shou ld be
su rgical enteric–p ancreatic d u ct anastom osis (Fig. 43.1). p erform ed w hen hyp ergastrinem ia is p resent. Som ato-
Enu cleation resu lts in higher fistu la rates than d istal p an- statin receptor scintigrap hy is very useful to d efine the
createctom y in m ost stu d ies (9–12), bu t these leaks u su ally extent of d isease p reop eratively (Fig. 43.2). Intraop erative
heal sp ontaneou sly w ithou t intervention. Alternatively, u ltrasonography is critical to the accu rate localization of
m alignant N ETs or tu m ors thou ght to carry a high risk of sm all N ETs w ithin the pancreas or d uod enum .
m alignant p rogression m ay requ ire m ajor p ancreatic Sim ilar to m any other su rgical p roced u res, m inim ally
resection. It is obviou sly d esirable to intervene early to invasive ap p roach es are increasin gly u tilized by exp ert
p revent m alignant sp read w hile p reserving p ancreatic end ocrin e su rgeon s for p an creatic end ocrine n eop lasm s.
fu nction and m inim izing m orbid ity and m ortality (from The lap aroscop ic ap p roach is w ell-su ited for sm all,
either cancer or su rgery) (1). The u niqu e asp ects of ben ign tu m ors. As w ith an y lap aroscop ic p roced u re, it is
end ocrine p ancreatic tu m ors that affect su rgical d ecision- fu nd am en tal to m aintain the sam e su rgical stand ard s for
m aking, ou tcom e, and frequ ency of p ostop erative com p li- oncologic resection th at are in p lace for op en p roced u res.
cations inclu d e the occu rrence of these neop lasm s in When tu m ors are know n to be ad vanced , involve signifi-
you ng p atients w ith norm al, soft, nonfibrotic p ancreatic can t stru ctu res, or carry sign ificant m align ant p otential,
p arenchym a; the u su al absence of d ilated p ancreatic and th e op en ap p roach is still p referred by m ost. Althou gh
Chapter 43 • Complications in Endocrine Pancreatic Surgery 569
FIGURE 43.2. Preoperative imaging for malignant tumor resection planning. This patient had a large tumor of the body and tail of the
pancreas with liver metastases. The CT scan shown demonstrated the anatomic relationships of the disease, and the somatostatin
receptor scintigraphy (right panel) showed the extent of the disease and the absence of other distant sites. An operative resection that
addressed all the demonstrated tumor was designed and carried out. The patient has remained a long-term, disease-free survivor from
this high-grade neuroendocrine tumor producing vasoactive intestinal peptide.
lap aroscop y afford s a qu icker recovery and shorter hos- com p lication rates th an cases that are in itiated as op en
p ital stay (9,13–15), attention m u st be p aid to p otential p roced u res (16). Cu rrently, conversion rates for lap aro-
d ifferences in m orbid ity and m ortality betw een the tw o scop ic p ancreatic end ocrine su rgery range from 5% to
grou p s. Man y cen ters have rep orted th at lap aroscop ic 30% w ith a m ed ian of 8.2% (9,12–19). As the lap aroscop ic
rem oval of p an creatic end ocrin e n eop lasm s resu lts in ap p roach gains su p p ort, sou nd su rgical ju d gm ent m u st
com p lication s th at are sim ilar to op en su rgery (Table be ap p lied to each p atient to d eterm ine the op tim al ini-
43.1) and op erative tim es are equ al or shorter than op en tial su rgical ap p roach based on th e su rgeon’s exp erien ce
su rgery (13,14). H ow ever, som e stu d ies also su ggest that and com fort as w ell as the characteristics of the p atient’s
cases con verted from lap aroscop ic to op en h ave high er d isease.
Table 4 3 .1 Com p lica t ion ra t es of la p a r oscop ic ver su s op en r esect ion of p a n cr ea t ic en d ocr in e t u m or s

All Complications Pancreatic Fistula
Author(s) (Year) n Open (%) Lap (%) Open (%) Lap (%) Conv (%)
Liu et al. (2007) (13) 52 36 28
Gumbs et al. (2008) (14) 31 69 67 38 24
Roland et al. (2008) (15) 37 29.4 20 5.9 15
España-Gómez et al. (2009) (16) 34 23.1 28.6 85.7
Average 38.5 44.8 38.3 22.3 22.5 85.7
Open, open approach; Lap, laparoscopic approach; Conv, conversions from laparoscopic to open.
■ COMPLICATIONS OF ENDOCRINE 80% of fistu lae are su ccessfu lly treated u sing nonop era-
tive m anagem ent (23,32), som e p reviou s stu d ies have sug-
PANCREATIC SURGERY
gested that 20% to 26% of p ancreatic fistu las (p rim arily in
■ Pancreatic or biliary fistula p atients w ith ad enocarcinoma) w ere d irectly related to
p atient m ortality (24,27).
Failu re of healing of the enteric–p ancreatic or enteric– Many d ifferent surgical techniques and managem ent
biliary anastom osis or a p arenchym al leak from the raw strategies have been proposed to d ecrease fistula rates in
p ancreatic su rface, m anifested as a p ancreatic or biliary pancreatic surgery. A number of operative techniques have
fistu la, is a com m on cau se of m orbid ity follow ing either been ad vocated to reduce the frequency of pancreatic fistula,
enu cleation or regional p ancreatic resection. The p otential including inversion pancreaticojejunostomy, mucosa-to-
for p ersistent d rainage of enzym e-rich flu id follow ing any mucosa pancreatic–jejunal anastomosis, or a d efunctional-
d isru p tion of the p ancreatic p arenchym a, inclu d ing local ized Roux-en-Y jejunal loop to drain the enteric–pancreatic
enu cleation of sm all N ETs, is w ell recognized . In 2005, the anastomosis. There is no consensus on typ e of anastom osis,
International Stu d y Grou p on Pancreatic Fistu la (ISGPF) and choice typ ically d ep end s on su rgeon com fort and
stand ard ized the d efinition of a p ostop erative p ancreatic exp erience (33). External or internal stent d rainage is also
fistu la as any m easu rable volu m e of d rain flu id on or after u nd er d ebate. A rand om ized controlled trial of 258 p atients
p ostop erative d ay 3 w ith an am ylase content greater than com p ared the u se of variou s sized internal stents w ith the
three tim es the u p p er norm al seru m valu e (20). Fistu lae u se of no stent and rep orted no statistically significant d if-
are then grad ed A, B, or C based on clinical criteria. Grad e ference in fistu la rates, com p lications, or m ortality betw een
A ind icates a “transient fistu la” that has no clinical the grou p s (34). There is also no consensu s on the optim al
im p act; grad e B fistu lae requ ire a change in m anagem ent m ethod of p ancreatic stu m p closu re after d istal p ancreatec-
(antibiotics, som atostatin, and d elay in d ischarge); and tomy. Som e ad vocate stap le closu re (w ith or w ithout rein-
grad e C fistu lae necessitate a m ajor change in m anage- forcem ent), others ad vocate variou s m ethod s of hand sew n
m ent (inclu d ing intensive care u nit m anagem ent and closu re, w hile others have show n no significant d ifference
invasive d rain p lacem ent) (20). In large stu d ies u sing the betw een m ethod s (22,33). The u se of new er biologic
ISGPF d efinition, abou t half (44% to 68%) of p ancreatic sealants (fibrin glu e, BioGlu e ®, neop rene, etc.) on p ancre-
fistu lae are grad e A and have no effect on p atient ou t- atico-enteric anastom oses and raw p ancreatic su rfaces has
com e; how ever, grad es B (25% to 52%) and C (4% to 7%) also failed to d em onstrate any significant d ifference in fis-
fistu lae affect m orbid ity and m ortality (21,22). The risk of tu la rates in three rand om ized controlled trials and one ret-
d evelop ing a clinically significant p ancreatic fistu la rosp ective review (33,35–38).
(grad e B or C) m ay be related to the p roxim ity of the enu - The use of long-acting somatostatin analogs, such as
cleation or resection to the m ajor p ancreatic d u ctal system octreotid e acetate or lanreotid e, either to d ecrease the inci-
or to the su rgical techniqu e u sed in d ivid ing the p ancre- d ence of postoperative pancreatic fistula or to improve heal-
atic p arenchym a. Other factors of p otential im p ortance ing of established pancreatic fistulas, has been controversial.
inclu d e w hether sim p le external d rainage of the excision In conjunction with restriction of oral intake and nasogastric
site is em p loyed versu s constru ction of a su rgical d ecompression, the rationale for pharmacologic treatment to
enteric–p ancreatic anastom osis. The p resence or absence d ecrease pancreatic secretion is that fistulas w ith a low er vol-
of p roxim al p ancreatic d u ct obstru ction is also an im p or- ume of output should be more likely to heal. Other pharma-
tant factor in healing of the line of p ancreatic d ivision or cologic agents have been employed to d ecrease gastric and
d isru p tion. pancreatic secretion, including loperamid e, atropine, piren-
The exp erience from p reviou s large series of p atients zepine, H 2-receptor antagonists, and omeprazole or other
und ergoing p ancreaticod u od enectom y for ad enocarci- proton-pump inhibitors, but their effectiveness has yet to be
noma in centers of excellence can be cited as a general established. Long-acting somatostatin analogs, such as
benchm ark of the exp ected risk of pancreatic fistula follow - octreotide acetate, have been evaluated in many random-
ing pancreatic resection for end ocrine tu m ors. In stud ies of ized controlled trials for efficacy in red ucing com plications
patients treated for ad enocarcinom a, the incid ence of p an- follow ing pancreatic surgery. The interpretation of the avail-
creatic fistu la ranges from 2% to 25% (20,21,23–29). In able data is complicated by differences in the patient charac-
patients u nd ergoing d istal pancreatectom y, the fistu la rate teristics of the stud y populations, the underlying disease
ranges from 5% to 29% (22). Pancreatic fistula rates follow - processes, the d efinition of a pancreatic leak or fistula, and
ing resection of pancreatic end ocrine tu m ors seem to be variability in the method, timing, and dosage of octreotide
som ew hat higher (range 9.5% to 64.3%, m ed ian 16.6%) ad ministration. H ow ever, the majority of recent studies and
(9–19,30,31) (Table 43.2). The w id e range of reported p an- meta-analyses conclud e that somatostatin analogs have no
creatic fistu la rates can be p artly attributed to lack of u se of effect on fistula rates or m ortality (37,39–41). Tw o recent
a stand ard ized d efinition (ISGPF) of pancreatic fistu la in meta-analyses review ed a total of 11 rand omized controlled
earlier stu d ies. Pancreatic fistulae are a frequ ent cau se of trials from 1995 to 2005, and both agree that somatostatin
morbid ity follow ing p ancreatic su rgery and are associated and its analogs do not significantly reduce postoperative
w ith increased costs and p rolonged hosp ital stay. Althou gh complications or pancreatic fistulae (37,41). More recent
Table 4 3 . 2 Com plica tion ra t es in ser ies of p a t ien ts u n der goin g r esect ion of pa n cr ea t ic en docr in e t u m or s
Panc Bili Fluid Postop
Overall Fist Fist Abs Col DGE WI Bleed Pulm Other Re-op Death
Author(s) (Year) n Type (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%)
Phan et al. 50 PETs 24.0 9.0 7.0 15.0 24.0 2.0
(1997) (2)
Park et al. 30 I 15.0 4.0 4.0 8.0 4.0 12.0 0.0
(1998) (45)
Lairmore et al. 21 PETs 9.5 4.8 14.0 9.5 4.8 4.8 9.5 4.8
(2000) (1)
Guo et al. 41 I 20.0 15.8 5.4 8.3 9.5 13.8 4.4 4.8 8.0 2.4
(2004) (46)
Toniato et al. 12 I 33.3 25.0 8.3
(2006) (18) (L)
Liu et al. (2007) (13) 52 I 32.7 11.5 5.8 9.6 5.8 1.9 3.8 3.8 3.8 0.0
Vagefi et al. 168 PETs 40.5 18.5 2.4 2.4 0.6 16.7 0.0
(2007) (30)
Liu et al. (2007) (31) 33 PETs 36.4 15.2 3.0 3.0 9.1 6.1 3.0 6.1 6.1
Sweet et al. 14 I 64.3
(2007) (19) (L)
Gumbs et al. 31 PETs 67.7 32.3 16.1 6.5 3.2 12.9 16.1 0.0
(2008) (14)
Fernández-Cruz 49 PETs 31.1 22.2 2.2 2.2 4.4 0.0
et al. (2008) (9) (L)
Roland et al. 37 I 24.3 10.8 2.7 10.8 0.0
(2008) (15)
Nikfarjam et al. 61 I 26.2 18.0 1.6 8.2 1.6 3.3 1.6 8.2 0.0
(2008) (10)
You et al. 90 PETs 17.8 2.2 0.0
(2009) (11)
Isla et al. (2009) 23 I 14.3
Luo et al. 29 I 17.2 13.8 0.0 3.4 0.0 0.0
(2009) (12) (L)
España-Gómez . 34 I 67.6 38.2 11.8 26.5 2.9
et al. (2009) (16)
633
Total (average) 46 34.6 21.8 5.6 5.3 7.9 6.4 8.5 3.9 3.6 10.2 6.5 0.9
Total (median) 37 31.9 16.9 5.1 3.4 7.0 9.1 7.1 4.0 3.8 8.9 5.0 0
L, laparoscopic resections only; Panc Fist, pancreatic fistula; WI, wound infection; I, insulinomas; Bili Fist, biliary fistula; Bleed, bleeding/transfusion; PETs, pancreatic
endocrine tumors; Fluid Col, intra-abdominal fluid collection; Pulm, pulmonary complications; DGE, delayed gastric emptying; Re-op, operation in early postoperative period;
Postop Death, postoperative death.
series report similar find ings (39,40). Although no clear d uct or vascular structures. If concern for d ivision of a major
benefit has been d emonstrated, many still advocate use of pancreatic d uct or concern for pancreatic leak exists, some
somatostatin analogs in select patients. have ad vocated ad ministration of secretin intravenously
Small, circumscribed pancreatic N ETs may be enucle- and inspection for increased pancreatic secretion from the
ated. Transection of the pancreatic parenchyma is usually cu t su rface of the p arenchym a. For enu cleations or local
performed by a combination of electrocautery and ligation p ancreatic resections d eem ed to be at significant risk for
of apparent pancreatic d uctal or vascular structures. Intraop- d evelop m ent of p ancreatic fistu la, ap p roxim ation w ith a
erative ultrasound is a valuable method to define the prox- portion of vascularized omentum or construction of enteric–
imity of an intrapancreatic neoplasm to the major pancreatic p ancreatic d rainage shou ld be consid ered .
Table 4 3 .3 Com p lica t ion r a t es r ela t ed t o t yp e of r esect ion of p a n cr ea t ic en d ocr in e t u m or s

All Complications Pancreatic/Biliary Fistula
Author(s) (Year) n E (%) DP (%) PD (%) E (%) DP (%) PD (%) Other (%)
Lairmore et al. (2000) (1) 21 80 27.3 100 0 9.1 40
Guo et al. (2004) (46) 41 33 9.1 20 33 9 10
Fernández-Cruz et al. (2008) (9) 49 42.8 22 38 8.7
Nikfarjam et al. (2008) (10) 61 23.8 12.5 20.0 16.7
You et al. (2009) (11) 90 4 11 44
Luo et al. (2009) (12) 29 22.2 0
Average 40.0 17.4 54.7 23.4 7.9 23.3 16.7
E, enucleation; DP, distal pancreatectomy; PD, pancreaticoduodenectomy; Other, other pancreatic resections.
As a group, patients w ith endocrine pancreatic tumors pancreas. Patients und ergoing major pancreatic resection or
have significant anatomic and physiologic d ifferences com- enucleation of pancreaticod uod enal N ETs d evelop the
pared to patients w ith pancreatic ad enocarcinoma. Patients expected postoperative complications, includ ing pancreatic
w ith pancreatic NETs occurring in the setting of one of the or biliary fistulas, peripancreatic abscess, wound complica-
hered itary end ocrine neoplasia synd romes (MEN 1 and von tions, bleed ing, and cardiopulmonary complications, at
H ippel-Lind au) are often d iagnosed early as a result of rates ranging from 17% to 67% (9–19,30,31) (Table 43.2).
prospective screening. Sporad ic pancreatic N ETs are rela- H ow ever, as a group, these patients are more likely to have
tively rare entities that are frequently diagnosed in young the attributes of younger age, few er associated medical con-
patients. These patients are more likely to have soft pancre- d itions, and greater physiologic reserve to overcome these
atic tissue without fibrosis or calcification and nondilated complications. Nonoperative m anagement of pancreas-
pancreatic and biliary d ucts. Soft pancreatic parenchyma associated complications is nearly always successful in these
and a small pancreatic duct ( 3 mm) increase the overall patients, and overall outcomes are excellent.
incid ence of pancreatic fistula (21,42–44) but do not increase
the incidence of clinically significant (grades B and C) fistu-
■ Intra-abdominal abscess/peripancreatic
lae (21). Importantly, these patients are also more likely to
have few er med ical comorbid ities and greater physiologic
fluid collection
reserve to overcome potential surgical complications. These Ap p roxim ately 80% of p atients w ith p ancreatic fistula fol-
clinical featu res significantly affect op erative d ecision- low ing p ancreatic resections heal w ith nonop erative m an-
making, technical concerns, and postoperative outcome. It is agem ent (23,32). N onop erative m anagem ent m ay inclu d e
interesting to note that the overall rate of postoperative pan- bow el rest, total p arenteral nu trition, p harm acologic inter-
creatic fistula rate in stud ies of patients und ergoing pancre- vention (octreotid e, H 2-recep tor antagonists, etc.) w here
aticod uodenectomy for malignant disease is similar or even ind icated , local w ou nd and skin care, infection control, and
low er than fistula rates in patients w ith N ETs und ergoing a continu ed closed -su ction external d rainage u ntil the fistu la
variety of, often less-invasive, pancreatic proced ures (enu- ou tp u t d ecreases to a m inim al volu m e. Ap p roxim ately 10%
cleation, d istal pancreatectomy, and pancreaticod uod enec- to 30% of p atients m ay requ ire im age-gu id ed p lacem ent of
tomy) w ith or w ithout construction of a pancreatic–enteric p ercu taneou s d rainage catheters, to rem ove u nd rained or
anastomosis (1,2,23–29,45,46). As mentioned earlier, patients locu lated p erip ancreatic flu id collections (32). Ap proxi-
w ith pancreatic N ETs are likely to be younger, w ith few er m ately 5% to 13% of patients d evelop severe sequ elae,
medical comorbid ities, nond ilated pancreatic/ biliary d ucts, inclu d ing sep sis, bleed ing, or d evelop m ent of a p ancreatic
and normal, soft, nonfibrosed pancreatic parenchyma. In abscess, that requ ire op erative intervention (32).
ad dition to these characteristics, NETs are more likely to be Pancreatic d uctal d isru ption and anastomotic failure
treated by enucleation than more formal resections, result- resu lt in leakage of p ancreatic exocrine secretions, inclu d -
ing in the slightly higher fistula rates associated w ith enucle- ing p ancreatic p roteases and lip ase, that resu lt in severe
ation (Table 43.3). Although fistula rates are higher for inflam m atory changes, fistu la form ation, and tissu e necro-
enucleation, most resolve spontaneously w ith little morbid - sis su rrou nd ing the p ancreas. The resu lt m ay be a loculated
ity (19). Therefore, even though only a subset of patients p erip ancreatic flu id collection or, w ith the ad d ition of bac-
w ith N ETs requires major pancreatic resection or construc- terial su p erinfection, intra-abd om inal abscess, or sep sis.
tion of a pancreatic–enteric anastomosis to adequately excise The treatm ent of intra-abd om inal abscess requ ires ap p ro-
the tumor, perhaps the slightly higher overall fistula rates p riate intravenou s antibiotics, in com bination w ith ad e-
are due to the combination of enucleation on a soft, normal qu ate p ercu taneou s or op erative d rainage.
The d evelopment of a postoperative intra-abd ominal of exocrine or end ocrine function. The d egree of impair-
abscess follow ing pancreatic resection is associated w ith ment is related to both the extent of pancreatic parenchyma
increased mortality and is clearly associated w ith the occur- resected and the fu nctional state of the resid u al pancreas.
rence of a leak from the p ancreatic or biliary anastom osis. Enu cleations or limited p ancreatic resections w ould be pre-
Follow ing pancreaticod uod enectomy for m alignant d is- d icted to carry minimal risk for d isturbance of d igestive or
ease, approxim ately 50% of intra-abd om inal abscesses are end ocrine pancreatic fu nction, althou gh related proced ures
associated w ith leakage from the pancreatic anastomosis that affect gastric or biliary secretion m ay also cause d ys-
(23). Less frequently, abscess formation results from anasto- function d ue to alterations in the intricate balance of the
motic failure of the hepaticojejunostomy or the gastroje- hormonal and electrolyte physiology of the upper gastroin-
junostomy. Peripancreatic fluid collections may also occur testinal tract. For instance, the ad d ition of partial gastrec-
after enucleation and m ay d evelop as an area of locu lated tom y to a pancreatic resection resu lts in fu rther im p airm ent
fluid that d oes not communicate effectively w ith the surgi- in the release of gastrin, pancreatic polypeptid e, and chole-
cally placed closed -suction d rain. Small fluid collections are cystokinin, w ith resultant effects on overall exocrine d iges-
commonly seen on computed tomography (CT) scans fol- tive fu nction.
lowing pancreatic surgery, and most are clinically insignifi- The influ ence of d ifferent su rgical p roced u res on
cant in the absence of systemic signs of toxicity or sepsis. p ancreatic exocrine fu nction has been investigated in a
In series of patients undergoing a variety of procedures few clinical stu d ies. In p atients u n d ergoing a p yloru s-
for resection of neuroendocrine pancreatic or duodenal p reserving p ancreaticod u od enectom y, resu lts follow ing
tumors (1,2,9,10,15,30,45,46), the incidence of intra-abdominal p ancreaticojeju nostom y versu s p ancreaticogastrostom y
abscess formation is approximately 2% to 14% and is related w ere com p ared by Jang et al. (48). A significant d eteriora-
to, but somewhat less frequent than, the occurrence of pancre- tion of pancreatic exocrine fu nction w as seen in patients
atic or biliary fistula due to anastomotic failure (Table 43.2). w ho w ere treated w ith p ancreaticogastrostom y com p ared
to p atients u nd ergoing p ancreaticojeju nostom y. The pro-
p osed m echanism w as early d eactivation of pancreatic
■ Metabolic disorders enzym es by gastric acid . Tran et al. (49) d em onstrated that
Op erative p roced u res involving the p ancreas carry the the extent of postoperative exocrine p ancreatic insu ffi-
potential for ad verse sequ elae relating to exocrine or ciency strongly correlated w ith p reop erative fibrosis. In
end ocrine p ancreatic function. Postoperative p ancreatic p atients requ iring oral su p p lem entation w ith p ancreatic
fu nction is d eterm ined by the extent of organ resection, the exocrine enzym es follow ing p ancreatic su rgery, treatm ent
und erlying d isease p rocess, and any preexisting abnorm al- w ith p roton-p u m p inhibitors is ind icated to avoid enzym e
ities of end ocrine and exocrine function (47). Few scientific d egrad ation by gastric acid .
stu d ies available in the literatu re sp ecifically ad d ress p re- Distu rbances of end ocrine secretion may also occu r fol-
operative risk factors, the relative risk related to the extent low ing op erative p roced u res on the p ancreas. Diabetes
of p ancreatic resection, and a rigorou s review of su rgical m ellitu s m ay occu r after resection of 60% to 75% of the
ou tcom es. p ancreatic p arenchym a, esp ecially in p atients w ith preex-
In general p hysiologic term s, the pancreas has d igestive isting im p airm ent of glu cose hom eostasis. The m ost chal-
fu nctions (exocrine secretion in the postprand ial state), lenging sequ ela of m ajor p ancreatic resection is recu rrent
end ocrine function centered on glucose hom eostasis and hyp oglycem ia, w hich m ay resu lt from increased postop er-
tight regu latory control of insu lin secretion and cou nter- ative insu lin sensitivity d u e to concomitant d ecrease in
regu latory horm ones, and the interd igestive phase of p an- glu cagon secretion (47).
creatic secretion. Both the d igestive and interd igestive
phases of exocrine and end ocrine pancreatic fu nction are
affected by m ajor pancreatic resection and are related to the
■ General complications
extent of resection as w ell as the presence of u nd erlying General postoperative complications occur follow ing opera-
d eficiencies. tion for endocrine pancreatic tumors w ith a frequency that is
Exocrine or end ocrine pancreatic insufficiency occurs expected for similar open, upper-abdominal procedures for
follow ing operative intervention for either chronic pancre- either malignant or benign processes. N ot surprisingly, these
atitis or excision of pancreatic malignancies. Varying general operative risks are related to the patient’s overall
d egrees of pancreatic d ysfunction exist in patients w ith health and the existence of associated med ical cond itions.
chronic pancreatitis prior to any surgical intervention. Because these general surgical risks are not unique to either
Resection of pancreatic tu m ors m ay be requ ired in p atients the decision-making or specific techniques employed for
w ith either normal or altered preoperative pancreatic func- resection of endocrine pancreatic neoplasms, these risks w ill
tion. Postoperative d eficits in exocrine or end ocrine secre- be acknow led ged but not d iscussed in d etail.
tion are d ue to a combination of preexisting d isease and Bleed ing m ay occu r w ith either an early or a late tim e
sequelae that are proced ure-related . The specific type of cou rse follow ing p ancreatic su rgery. Early bleed ing m ay be
surgical proced ure and the magnitud e of pancreatic resec- associated w ith technical failu re of the su tu re ligation of a
tion have a d irect relationship to postoperative impairment sm all venou s or arterial vessel, technical failu re of any of
several tissu e coagu lation m ethod s cu rrently u sed to steroid use, increase the risk of wound infection. Superficial
d ivid e surround ing soft tissues containing an intricate vas- or deep wound infection occurred in an average of 8.5% of
cu lar su p p ly, or bleed ing related to constru ction of a su rgi- 775 patients undergoing resection of pancreatic endocrine
cal anastom osis. Anastom otic bleed ing m ay be m anifested tumors in the collected series summarized in Table 43.2.
as hem atobilia, intralum inal gastrointestinal bleed ing, or Wound infection rates ranged from approximately 1% to
intra-abd om inal bleed ing. Late bleed ing (after postop era- 24%, with the highest rates in stud ies involving more com-
tive d ay 5) is m ore likely to result from com plications relat- plex resections (pancreaticoduodenectomy) (2). The inci-
ing to the d evelop m ent of a pancreatic fistu la, su ch as dence of DVT was not consistently addressed in the available
ru pture of an arterial pseud oaneu rysm, or erosion of a series of patients undergoing resection of pancreatic
large vessel. Alternatively, late gastrointestinal bleed ing endocrine neoplasms; however, these patients appear to be at
may be associated w ith m arginal ulceration follow ing con- lower risk than patients with adenocarcinoma of the pan-
stru ction of a gastrojejunostom y. It is reasonable to assu m e creas. Finally, the frequency of cardiopulmonary or other
that the risk of p ostop erative bleed ing relating d irectly to a major complications in the collected series of patients w ith
technical failu re shou ld be associated w ith the m agnitu d e endocrine pancreatic tumors averaged 10%, with an average
of the requ ired d issection and the need to secu re m u ltip le mortality of 0.9% (Table 43.2). In the reviewed series of 775
sm all vessels, the need to perform a m ajor regional pancre- patients there were four d eaths, three follow ing pancreatico-
atic resection w ith d ivision of the pancreatic p arenchym a, duod enectomy and one due to pulmonary embolism. All
or the requ irem ent for the constru ction of mu ltip le su rgical four cases were also associated with severe preoperative
anastomoses. Becau se resection of pancreaticod u od enal medical limitations.
N ETs m ay frequ ently be successfully p erform ed w ithou t
major p ancreatic resection, the risk of m ajor postoperative
bleed ing w ou ld be expected to be low. Ind eed , in the col- ■ SUMMARY
lected series of 775 p atients u nd ergoing resection of N ETs N ETs of the p ancreas are infrequ ent neop lasm s that m ay
reported in Table 43.2, the incid ence of significant bleed ing occu r sp orad ically or in association w ith one of several
requ iring transfu sion w as only 3.9%. hered itary end ocrine neop lasia synd rom es. Many p atients
Delayed gastric em p tying is a very frequ ent cau se of w ith N ETs, esp ecially in the fam ilial setting, are d iagnosed
morbid ity follow ing p ancreaticod uod enectom y for ad eno- at a you ng age in the absence of significant m ed ical com or-
carcinom a of the p ancreas, occurring in u p to one-third of bid ities. Fu rtherm ore, neu roend ocrine p ancreatic tu m ors
patients (23,50). Park et al. (50) d em onstrated tw o ind e- are m ore likely to occu r in association w ith soft, nonfi-
pend ent factors for d elayed gastric em ptying: clinically rel- brotic p ancreatic p arenchym a and w ithou t associated d ila-
evant pancreatic fistu lae (grad e B/ C) and benign tion of the p ancreatic or biliary d u cts com p ared to p atients
pathology. Delayed gastric em ptying m ay be d efined as the w ith ad enocarcinom a. The u niqu e featu res of fam ilial
need for gastric d ecom pression for 10 d ays postop era- end ocrine p ancreatic tu m ors, su ch as those occu rring in
tively. Patients u nd ergoing resection of end ocrine p ancre- the MEN 1 synd rom e, inclu d e m u ltifocal involvem ent
atic tu m ors d evelop d elayed gastric em ptying w ith w ithin a target tissu e and the d evelop m ent of tu m ors in
red uced frequ ency (approxim ately 6.4%) (Table 43.2). Most m u ltip le target organs. As a general ru le, m any p ancreatic
patients p resent w ith persistent nau sea, abd om inal fu ll- N ETs p u rsu e a relatively ind olent cou rse, althou gh a su b-
ness, early satiety, or the need for nasogastric tube reinser- set m ay m etastasize and resu lt in significant m orbid ity
tion in the first w eek postoperatively. Poor gastric and m ortality. Su rgical d ecision-m aking in these p atients
em ptying m ay occu r follow ing any pancreatic proced ure, shou ld be based on the u niqu e featu res of these u ncom -
bu t is frequ ently seen w hen a gastrojeju nostom y has been m on neop lasm s, the exp ected natu ral history, and the
constru cted . Inad equ ate gastric emp tying is m ultifactorial m ost significant op erative risks. The m ost im p ortant of
and m ay occu r even w hen a w ater-solu ble contrast stu d y these are the risks of p ostop erative p ancreatic fistu la for-
d em onstrates a p atent gastrojejunostom y, w ith or w ithou t m ation and the d evelop m ent of p erip ancreatic abscess and
associated anastom otic ed em a. Ad equ ate treatm ent u su - su bsequ ent sep sis. The id eal su rgical treatm ent of p ancre-
ally involves continued gastric d ecom pression, ju d iciou s atic N ETs relieves the p atient of significant risk of m alig-
use of p rokinetic agents, enteral or parenteral feed ing as nant p rogression w hile p reserving p ancreatic end ocrine
ind icated , and p atience u ntil oral feed ing can be reinitiated . and exocrine fu nction and m inim izing m orbid ity from
Other complications, includ ing wound infections, DVT, either su rgery or the u nd erlying d isease p rocess.
and significant cardiac or pulmonary events, may also occur
follow ing endocrine pancreatic surgery. Wound infections
follow ing operation for pancreatic endocrine tumors occur ■ REFERENCES
with rates similar to other patients undergoing upper- 1. Lairm ore TC, Chen VY, DeBened etti MK, et al. Du od enop ancreatic
abdominal operation w ith or w ithout division of the gas- resections in p atients w ith m u ltip le end ocrine neop lasia typ e 1. Ann
trointestinal tract. Coexistent disorders, including morbid Surg 2000;231:909–918.
2. Phan GQ, Yeo CJ, Cam eron JL, et al. Pancreaticod u od enectom y for
obesity, diabetes, collagen vascular disease, and immunosup- selected periam p ullary neu roend ocrine tu m ors: fifty p atients. Surgery
pression secondary to underlying med ical conditions or 1997;122:989–997.
3. Ekeblad S, Skogseid B, Du nd er K, et al. Prognostic factors and su rvival 29. Cullen JJ, Sarr MG, Ilstru p DM. Pancreatic anastom otic leak after p an-
in 324 p atients w ith p ancreatic end ocrine tu m or treated at a single creaticod u od enectom y: incid ence, significance, and m anagem ent. Am J
institu tion. Clin Cancer Res 2008;14(23):7798–7803. Surg 1994;168(4):295–298.
4. Moley JF, Lairm ore TC, Phay J. H ered itary end ocrinop athies. Curr 30. Vagefi PA, Razo O, Deshp and e V, et al. Evolving p atterns in the d etec-
Probl Surg 1999;36:653–764. tion and ou tcom es of p ancreatic neu roend ocrine neop lasm s. Arch Surg
5. Knu d son AG Jr, H ethcote H W, Brow n BW. Mu tation and child hood 2007;142:347–354.
cancer: a p robabilistic m od el for the incid ence of retinoblastom a. Proc 31. Liu H , Zhang S, Wu Y, et al. Diagnosis and su rgical treatm ent of p an-
Natl Acad Sci USA 1975;72:5116–5120. creatic end ocrine tu m ors in 36 p atients: a single-center rep ort. Chin Med
6. Lairm ore TC, Piersall LD, DeBened etti MK, et al. Clinical genetic test- J 2007;120(17):1487–1490.
ing and early su rgical intervention in p atients w ith m u ltip le end ocrine 32. Munoz-Bongrand N , Sau vanet A, Denys A, et al. Conservative m an-
neop lasia type 1 (MEN 1). Ann Surg 2004;239:637–647. agem ent of p ancreatic fistu la after pancreaticod u od enectom y w ith
7. Akerstrom G, H essm an O, Skogseid B. Tim ing and extent of su rgery in pancreaticogastrostom y. J Am Coll Surg 2004;199:198–203.
sym ptom atic and asym ptom atic neuroend ocrine tum ors of the pan- 33. Shrikhand e SV, D’Sou za MA. Pancreatic fistu la after p ancreatectom y:
creas in MEN 1. Langenbecks Arch Surg 2002;386(8):558–569. evolving d efinitions, p reventive strategies and m od ern m anagem ent.
8. Dralle H, Krohn SL, Karges W, et al. Surgery of resectable nonfunctioning World J Gastroenterol 2008;14(38):5789–5796.
neuroend ocrine pancreatic tumors. World J Surg 2004;28(12):1248–1260. 34. Winter JM, Cam eron JL, Cam p bell KA, et al. Does p ancreatic d u ct
9. Fernánd ez-Cru z L, Blanco L, Cosa R, et al. Is lap aroscopic resection stenting d ecrease the rate of pancreatic fistula follow ing pancreatico-
ad equ ate in patients w ith neu roend ocrine p ancreatic tu m ors? World J d u od enectom y? Results of a p rosp ective rand om ized trial. J Gastroin-
Surg 2008;32:904–917. test Surg 2006;10(9):1280–1290.
10. N ikfarjam M, Warshaw AL, Axelrod L, et al. Im p roved contem porary 35. Lillem oe KD, Cam eron JL, Kim MP, et al. Does fibrin glu e sealant
su rgical m anagem ent of insu linom as: a 25-year exp erience at the Mass- d ecrease the rate of p ancreatic fistu la after p ancreaticod u od enectom y?
achu setts General H osp ital. Ann Surg 2008;247(1):165–172. Resu lts of a p rosp ective rand om ized trial. J Gastrointest Surg 2004;8(7):
11. You DD, Lee H G, Paik KY, et al. The ou tcom es after su rgical resection 766–772.
in pancreatic end ocrine tu m ors: an institu tional exp erience. Eur J Surg 36. Suc B, Mskia S, Fingerhu t A, et al. Tem p orary fibrin glu e occlu sion of
Oncol 2009;35:728–733. the m ain pancreatic d u ct in the p revention of intra-abd om inal com pli-
12. Lu o Y, Liu R, H u M, et al. Lap aroscop ic su rgery for p ancreatic insu lino- cations after p ancreatic resection: p rosp ective rand om ized trial. Ann
m as: a single-institu tion exp erience of 29 cases. J Gastrointest Surg Surg 2003;237(1):57–65.
2009;13:945–950. 37. Schu lick RD, Yoshim ura K. Stents, glu e, etc.: is anything p roven to help
13. Liu H , Peng C, Zhang S, et al. Strategy for the su rgical m anagem ent of prevent pancreatic leaks/ fistulae? J Gastrointest Surg 2009;13:1184–1186.
insu linom as: analysis of 52 cases. Dig Surg 2007;24:463–470. 38. Fisher WE, Chai C, H od ges SE, et al. Effect of BioGlu e® on the inci-
14. Gum bs A, Grès P, Mad u reira F, et al. Lap aroscop ic vs op en resection of d ence of p ancreatic fistu la follow ing p ancreas resection. J Gastrointest
p ancreatic end ocrine neop lasm ’s: single institu tion’s exp erience over Surg 2008;12:882–890.
14 years. Langenbecks Arch Surg 2008;393:391–395. 39. Kollm ar O, Moussavian MR, Richter S, et al. Prop hylactic octreotid e
15. Roland CL, Lo C, Miller BS, et al. Su rgical ap p roach and p erioperative and d elayed gastric em p tying after pancreaticod uod enectom y: results
com plications d eterm ine short-term outcom es in patients w ith insuli- of a prospective rand om ized d ouble-blind ed placebo-controlled trial.
nom a: results of a bi-institu tional stu d y. Ann Surg Oncol 2008;15(12): Eur J Surg Oncol 2008;34:868–875.
3532–3537. 40. Ram os-De la Med ina A, Sarr MG. Som atostatin analogu es in the p re-
16. Esp aña-Góm ez MN , Velázqu ez-Fernánd ez D, Bezau ry P, et al. Pancre- vention of p ancreas-related com p lications after p ancreatic resection. J
atic insu linom a: a su rgical exp erience. World J Surg 2009;33:1966–1970. Hepatobiliary Pancreat Surg 2006;13:190–193.
17. Arbu ckle JD, Kekis PB, Lim A, et al. Lap aroscop ic m anagem ent of 41. Zeng Q, Zhang Q, H an S, et al. Efficacy of som atostatin and its ana-
insu linom as. Br J Surg 2009;96:185–190. logues in prevention of postoperative com plications after pancreatico-
18. Toniato A, Med uri F, Foletto M, et al. Lap aroscop ic treatm ent of benign duodenectomy: a m eta-analysis of random ized controlled trials. Pancreas
insu linom as localized in the bod y and tail of the pancreas: a single-cen- 2008;36(1):18–25.
ter exp erience. World J Surg 2006;20:1916–1919. 42. Yang YM, Tian XD, Zhuang Y, et al. Risk factors of pancreatic leakage after
19. Sw eet MP, Izum isato Y, Way LW, et al. Lap aroscop ic enu cleation of pancreaticoduodenectomy. World J Gastroenterol 2005;11(16):2456–2461.
insu linom as. Arch Surg 2007;142(12):1202–1204. 43. DeOliveira ML, Winter JM, Schafer M, et al. Assessm ent of complications
20. Bassi C, Dervenis C, Bu ttu rini G, et al. Postop erative p ancreatic fistu la: after pancreatic surgery: a novel grading system applied to 633 patients
an international stu d y grou p (ISGPF) d efinition. Surgery 2005;138(1): undergoing pancreaticoduodenectom y. Ann Surg 2006;244(6):931–939.
8–13. 44. Bu ttu rini G, Daskalaki D, Molinari E, et al. Pancreatic fistu la: d efinition
21. Kaw ai M, Tani M, H irono S, et al. H ow d o w e p red ict the clinically rel- and cu rrent p roblem s. J Hepatobiliary Pancreat Surg 2008;15:247–251.
evant pancreatic fistu la after p ancreaticod u od enectom y?—an analysis 45. Park BJ, Alexand er H R, Libu tti SK, et al. Op erative m anagem ent of
in 244 consecu tive p atients. World J Surg 2009;33(12):2670–2678. islet-cell tum ors arising in the head of the pancreas. Surgery 1998;124(6):
22. Ferrone CR, Warshaw AL, Rattner DW, et al. Pancreatic fistu la rates 1056–1061; d iscu ssion 1061–1062.
after 462 d istal pancreatectom ies: stap lers d o not d ecrease fistu la rates. 46. Guo KJ, Liao H H , Tian YL, et al. Su rgical treatm ent of nonfu nctioning
J Gastrointest Surg 2008;12(10):1691–1697. islet cell tu m or: report of 41 cases. Hepatobiliary Pancreat Dis Int 2004;
23. Yeo CJ. Managem ent of com p lications follow ing p ancreaticod u od enec- 3(3):469–472.
tom y. Surg Clin North Am 1995;75(5):913–924. 47. Kahl S, Malfertheiner P. Exocrine and end ocrine p ancreatic insu ffi-
24. Braasch JW, Gray BN . Consid erations that low er p ancreatod u od enec- ciency after p ancreatic su rgery. Best Pract Res Clin Gastroenterol 2004;
tom y m ortality. Am J Surg 1977;133(4):480–484. 18(5):947–955.
25. Ed is AJ, Kiernan PD, Taylor WF. Attem p ted cu rative resection of d uctal 48. Jang JY, Kim SW, Park SJ, et al. Com p arison of the fu nctional ou tcom e
carcinom a of the pancreas: review of Mayo Clinic experience, after p yloru s-p reserving pancreaticod uod enectom y: p ancreaticogas-
1951–1975. Mayo Clin Proc 1980;55(9):531–536. trostom y and p ancreaticojeju nostom y. World J Surg 2002;26:366–371.
26. Grace PA, Pitt H A, Tom p kins RK, et al. Decreased m orbid ity and m or- 49. Tran TC, van’t H of G, Kazem eir G, et al. Pancreatic fibrosis correlates
tality after pancreatod u od enectom y. Am J Surg 1986;151(1):141–149. w ith exocrine pancreatic insu fficiency after pancreaticod uod enectom y.
27. Tred e M, Schw all G. The com p lications of p ancreatectom y. Ann Surg Dig Surg 2008;25(4):311–318.
1988;207(1):39–47. 50. Park JS, H w ang H K, Kim JK, et al. Clinical valid ation and risk factors
28. Cam eron JL, Pitt H A, Yeo CJ, et al. One hu nd red and forty-five consec- for d elayed gastric em p tying based on the International Stu d y Grou p
u tive pancreaticod u od enectom ies w ithou t m ortality. Ann Surg 1993; of Pancreatic Su rgery (ISGPS) Classification. Surgery 2009;146(5):
217(5):430–435; d iscu ssion 435–438. 882–887.
CHAPTER
44
Complications in Breast Surgery

Alicia Growney, Ahmad Azari, and Lisa A. Newman
■ INTRODUCTION Rare com plications can also occu r in conju nction w ith
variou s breast p roced u res and w ill not be d iscu ssed in
The breast is a relatively clean organ, com prised of skin, d ep th. For exam p le, p neu m othorax can be related either to
fatty tissue, and mammary gland ular elements that have no inad vertent pleu ral pu ncture d u ring w ire localization or to
d irect connection to any m ajor bod y cavity or visceral stru c- inad vertently d eep d issection w ithin an intercostal sp ace.
tu res. In the absence of concurrent m ajor reconstru ction Also, p atients can d evelop brachial p lexop athy related to
being p erform ed , breast surgery is generally not accom pa- stretch inju ry from p ositioning in the op erating room (1).
nied by large-scale fluid shifts, infectious complications, or The Am erican Society of Anesthesiology recom m end s
hemorrhage. Thus, the breast is largely perceived as being u p p er extrem ity p ositioning su ch that m axim al abd uction
associated w ith relatively low risk for surgical morbid ity. at the shou ld er is 90 d egrees, w ith neu tral forearm position,
The breast is, how ever, the site of the most common cancer and u se of p ad d ed arm board s (2).
afflicting American w omen, and a myriad of complications Mond or ’s d isease, or throm bosis of the thoracoepigas-
can occur in association w ith the proced ures d esigned to tric vein, can occu r sp ontaneou sly, or follow ing any breast
d etect and treat breast cancer. Some of these complications p roced u re su ch as lu m p ectom y or even p ercu taneou s nee-
are related to the breast itself, and others are associated w ith d le biop sy (3–7). While Mond or ’s d isease is not an estab-
axillary staging p roced ures. This chapter w ill ad d ress some lished breast cancer risk factor, there are case reports of
general nonspecific complications first (w ound infections, p atients w ho have p resented w ith this cond ition at the tim e
serom a form ation, and hem atom a), follow ed by d iscu ssions of their breast cancer d iagnosis (4). This cond ition typically
of complications that are specific to particu lar breast-related p resents as a p alp able, som etim es tend er cord ru nning ver-
proced u res: lu m pectom y (includ ing both d iagnostic open tically from the m id -low er hem isp here of the breast tow ard
biopsy and breast conservation therapy for cancer); m astec- the abd om inal w all. It is u su ally a self-lim ited cond ition,
tom y; axillary lym ph nod e d issection (ALN D); lym phatic and resolu tion can be exp ed ited by soft-tissu e m assage.
mapping/ sentinel lymph nod e biopsy; and reconstruction.
Finally, a few cond itions requiring special surgical consid er- Wound Infections
ations such as im m ed iate breast reconstruction (IBR) and Rates of p ostop erative infections in breast and axillary inci-
neoad juvant chemotherapy w ill be presented . sions have ranged from 1% of cases and to nearly 20%, as
show n in Table 44.1 (8–21). In 2007, El-Tam er et al. (22)
rep orted a stu d y based u p on the N ational Su rgical Qu ality
■ General wound complications related to
Im p rovem ent Program Patient Safety in Su rgery. They
breast and axillary surgery p rosp ectively collected inp atient and ou tp atient 30-d ay
As a p erip heral soft-tissu e organ, m any w ound com p lica- p ostoperative m orbid ity and m ortality d ata on patients
tions related to breast p roced ures are relatively m inor and u nd ergoing surgery (m astectom y or lum pectom y w ith an
frequ ently m anaged on an ou tpatient basis. It is therefore axillary p roced u re) at 14 u niversity and 4 com m unity cen-
d ifficu lt to establish accu rate incid ence rates for these ters. In a 30-d ay follow -u p of 3,107 p atients, the m ost fre-
events. As d iscu ssed below how ever, rep orted stu d ies d oc- qu ent m orbid com p lication fou nd w as w ou nd infection,
u m ent that surgical m orbid ity from breast and / or axillary w hich m ore com m only occu rs in the m astectom y (4.34%)
w ound infections, serom as, and hem atom as occur in u p to grou p versu s the lu m p ectom y grou p (1.97%). A m eta-
30% of cases. Very few of these require a prolongation of analysis by Platt et al. (23), in 1993, analyzed d ata on 2,587
hospital stay or a read mission for inpatient care. A fou rth surgical breast proced ures and fou nd an overall w ou nd
com plication, chronic incisional p ain, can also occur in con- infection rate of 3.8% of cases. Stap hylococcal organism s
junction w ith various su rgical breast proced u res. are u su ally im p licated in these infections (8,17), introd uced
via skin flora. Obesity, old er age, sm oking, d iabetes m elli-
tu s, m alignancy, and am ou nt of tissu e rem oval have been
Alicia Growney, Ahmad Azari, Lisa A. Newman: Univer- som e of the m ost consistently id entified risk factors for
sity of Michigan, Ann Arbor, MI 48109. breast w ou nd sep sis. Several investigators (11,14,21) have
576
Chapter 44 • Complications in Breast Surgery 577
Table 4 4 .1 Select ed st u d ies eva lu a t in g wou n d in fect ion ra t es follow in g br ea st su r ger y

No. of Type of Procedures Wound Study Findings/Risk Factors for
Study Cases Analyzed Type of Study Infection Rate Infection
Platt et al., 606 Lumpectomy Phase 3 study 9.4% Preoperative antibiotic coverage reduced
1990 (8) Mastectomy of preoperative wound infection rate (6.6% vs. 12.2%)
ALND antibiotics
Reduction
mammoplasty
Hoefer et al., 101 Mastectomy Retrospective 8.9% Risk factor:
1990 (9) review • Cautery
Wagman et al., 118 Mastectomy Phase 3 study 6.8% Preoperative antibiotics had no effect on
1990 (10) of preoperative wound infection rates (5% vs. 8%)
antibiotics
Chen et al., Mastectomy Retrospective 2.6%–11.1% Risk factors:
1991 (11) Lumpectomy review • Older age;
• Surgery performed in 1970s versus 1980s;
• Prior open diagnostic biopsy versus
single-stage surgery
Vinton et al., 560 Mastectomy Retrospective 15% (mastectomy) Risk factors:
1991 (12) Lumpectomy review 13% (lumpectomy) • Older age;
ALND • Mastectomy versus lumpectomy;
• Tobacco smoking;
• Obesity
Platt et al., 1,981 Mastectomy Retrospective 3.4% Preoperative antibiotic coverage reduced
1992 (13) Lumpectomy review wound infection rate (OR 0.59; 95%
ALND confidence interval 0.35–0.99)
Reduction
mammoplasty
Lipshy et al., 289 Mastectomy Retrospective 5.3% Risk factor:
1996 (14) review Prior open diagnostic biopsy versus
diagnostic needle biopsy (6.9% vs. 1.6%)
Preoperative antibiotic coverage reduced
wound infection rate
Bertin et al., 18 Cases Mastectomy Case–control NA Risk factors:
1998 (15) 37 Controls Lumpectomy • Obesity;
• Older age
Thomas et al., 1,766 Mastectomy Phase 3 study 0.6% Short-acting versus long-acting preoperative
1999 (16) Lumpectomy of preoperative cephalosporin (0.91% vs. 0.45%)
ALND antibiotics
Gupta et al., 334 Mastectomy Phase 3 study 18.3% Preoperative antibiotics had no effect on
2000 (17) Lumpectomy of preoperative wound infection rates (17.7% vs. 18.8%)
ALND antibiotics
Nieto et al., 107 Mastectomy Prospective 7% (mastectomy) Risk factors:
2002 (18) Lumpectomy observational 17% (lumpectomy) • Lumpectomy versus mastectomy;
ALND study • Older age;
• Obesity
Sorensen et al., 425 Mastectomy Retrospective 10.5% Risk factors:
2002 (19) Lumpectomy review • Tobacco smoking;
ALND • Diabetes mellitus;
• Obesity;
• Heavy ethanol consumption
(continued)
Table 4 4 .1 Select ed st u d ies eva lu a t in g wou n d in fect ion ra t es follow in g br ea st su r ger y (Continued)
No. of Type of Procedures Wound Study Findings/Risk Factors for
Study Cases Analyzed Type of Study Infection Rate Infection
Witt et al., 326 Mastectomy Prospective 15.3% Risk factors:
2003 (20) Lumpectomy observational • Older age;
ALND study • Obesity;
• Diabetes mellitus;
• Prior diagnostic core-needle biopsy
versus open diagnostic biopsy
• Preoperative antibiotic coverage reduced
wound infection rate
Tran et al., 320 Mastectomy Retrospective 6.1% Risk factors:
2003 (21) Lumpectomy review • Prior open diagnostic biopsy versus
diagnostic needle biopsy (11.1% vs. 9.7%)
Felippe et al., 354 Breast cancer Prospective 17% Risk factors:
2007 (3) cohort study • Drain in place
• Older age
• Skin flap necrosis
Gravante et al., 87 Breast reduction Retrospective 27.9% Risk factors:
2008 (2) review Smoking (OR 2.04)
Amount of removed tissue (OR: 4.7)
Olsen et al., 325 Mastectomy Retrospective 17.5% Risk factors:
2008 (8) Reconstruction case–control Implant or tissue expander placement
Reduction study Suboptimal prophylactic antibiotic
dosing
ALND, axillary lymph node dissection; NA, not applicable; OR, odds ratio.
found that patients u nd ergoing d efinitive surgery for can- greatest risk red u ction w ith the former (0.45% vs. 0.91%). In
cer had a low er risk for w ound infection if their d iagnosis contrast, Wagman et al. (10) fou nd no effect of p eriopera-
had been established by prior need le biopsy rather than an tive cep halosp orin in a p lacebo-controlled p hase 3 trial
open su rgical biop sy, yet one investigator found the op p o- involving 118 breast cancer p atients (5% vs. 8%); how ever,
site effect (20). N icotine and other com ponents of tobacco the infections am ong the antibiotic arm w ere d elayed in
cigarettes have w ell-know n ad verse effects on sm all ves- onset (17.7 vs. 9.6 d ays). Gu p ta et al. (17) rep orted sim ilar
sels of the skin, resu lting in a nearly fou rfold increase w ou nd infection rates in a p hase 3 stu d y of p rophylactic
in risk of w ou nd infection follow ing breast su rgery (19). am oxicillin/ clavu lanic acid (17.7%) versu s p lacebo (18.8%)
As d em onstrated by the variou s stu d ies su m marized in and conclu d ed that p eriop erative antibiotics are unneces-
Table 44.1, there is no consistent correlation betw een sary in elective breast su rgery. H all et al. (24) in a rand om -
w ou nd infection risk and m astectom y versu s lu m p ectom y ized clinical trial show ed that ad m inistration of a single
as d efinitive breast cancer surgery. d ose of flu cloxacillin failed to red u ce the rate of w ou nd
Use of p reop erative antibiotic coverage to m inim ize infection after nonreconstru ctive breast su rgery. H ow ever,
infection rates has been evalu ated in m u ltip le retrosp ec- in a system atic review and m eta-analysis by Tejirian et al.
tive as w ell as p rosp ective, rand om ized controlled trials. (25) regard ing u se of p rop hylactic antibiotics for p reven-
These stu d ies have yield ed d isp arate resu lts; m any have tion of w ou nd infection after breast su rgery, it w as con-
show n that a single d ose of a p reop erative antibiotic (u su - clud ed that prop hylactic antibiotics d id red u ce
ally a cep halosp orin, ad m inistered ap p roxim ately 30 m in- p ostop erative w ou nd infections in breast operations.
u tes p rior to incision) effectively red u ces w ou nd infection Becau se of these d isp arate resu lts, and in an attem pt to
rates by 40% (8,13,21,23), and the Platt et al. (23) m eta- avoid excessive cost as w ell as risk of p rom oting resistant
analysis revealed that antibiotic p rop hylaxis red u ced organism s, m any clinicians have ad op ted the p ractice of
w ou nd infection rates by 38%, d esp ite the selection bias of lim iting antibiotic p rophylaxis to high-risk p atients and to
antibiotics being p red om inantly u tilized in higher-risk cases involving foreign bod ies, su ch as w ire localization
cases. Fu rtherm ore, the low est rep orted rates of breast biop sies. Penel et al. (26) cond u cted a p rosp ective observa-
w ou nd infections occu rred in a p hase 3 stu d y (16) of a tional cohort stu d y and rep orted an 81% red u ction in fre-
long-acting versu s a short-acting cep halosp orin, revealing qu ency of su rgical site infection (3.5% vs. 0.8%) by using
prop hylactic cefuroxim e in high-risk/ selected p atients. for serom a form ation. The closed sp aces of lum pectom y
Desp ite this com m on p ractice, it shou ld be noted that w ire cavities, axillary w ou nd s, and the anterior chest w all cavity
localization proced ures have not been specifically id enti- left u nd er m astectom y skin flap s all harbor serom a. After a
fied as a w ou nd infection (21) risk factor. lu m p ectom y, this serom a is ad vantageou s to the patient, as
Mild incisional cellu litis can be treated w ith oral antibi- it usually preserves the norm al breast contour even after a
otics, bu t nonrespond ing or extensive soft-tissu e infection large-volu m e resection, eventu ally rep laced by scar form a-
requ ires intravenou s therap y. Ind elicato et al. (27) tion as the cavity consolid ates. Occasionally, the lum pec-
d escribed and reported the clinical entity of d elayed breast tomy serom a is overly exu berant, and if the patient
cellu lites (occu rring 3 m onths after breast conservation experiences d iscom fort from a bu lging fluid collection,
surgery) in 8% of their population of patients and believed sim p le asp iration of the excess is u su ally ad equ ate m an-
that it w as p rim arily related to bacterial infection in the set- agem ent.
ting of im p aired lym phatic d rainage. A m inority of breast Serom a form ation u nd er the skin flap s of axillary or
w ou nd infections p rogress into a fu lly d evelop ed abscess. m astectom y w ou nd s imp airs the healing p rocess, and
The p ointing, flu ctu ant, and exquisitely tend er m ass of a d rains are therefore u su ally left in p lace to evacu ate p ost-
breast abscess u sually becom es apparent 1 to 2 w eeks p ostop erative flu id collections. Most breast cancer su rgery is
operatively and occu r at a lu m pectom y, m astectom y, or p erform ed in the ou tp atient setting, and p atients m ust be
axillary incision site. When there is u ncertainty regard ing instru cted abou t p rop er d rainage catheter care. After 1 to 3
the d iagnosis (as m ay be the case w ith d eep -seated w eeks, the skin flap s heal and ad here to the chest w all, as
abscesses follow ing lum p ectom y), ultrasou nd im aging is evid enced by d im inished d rain ou tp u t. Serom a collections
occasionally help fu l, but the com plex m ass visu alized can that d evelop after d rain rem oval can be m anaged by p ercu -
app ear id entical to a consolid ating serom a or hem atom a. taneou s asp iration. Asp iration is u su ally w ell tolerated
Asp iration can also confirm the d iagnosis, bu t the p ossibil- becau se the mastectom y and axillary incisions tend to be
ity of sam pling error can m islead the clinician as w ell. insensate; these proced u res can be repeated as frequ ently
Definitive m anagem ent of an abscess requ ires incision and as necessary in ord er to ensu re that the skin flaps are
d rainage; cu rative aspiration of pu ru lent m aterial is rarely d ensely ad herent to the chest w all. Serom a aspiration is
successfu l, and the abscess generally reaccu m ulates. Usu - necessary in 10% to 80% of ALN D and m astectom y cases
ally, the incision and d rainage can be accom p lished by accord ing to rep orted series and as review ed in d etail by
reop ening the original surgical w ou nd , and the resu lting Pogson et al. (29). As p er a retrosp ective review, perform ed
cavity m u st be left open to heal by second ary intention. on 324 consecu tive breast cancer p atients w ho u nd erw ent
When recu rrent cancer is a concern, biopsy of the abscess of 561 breast and axillary p roced u re, by Boostrom et al. (28)
cavity w all is prud ent. in 2009, serom a requ iring intervention occu rs in 2% to 16%
Chronic recurrent periareolar abscess form ation (also of p atients after breast or axillary op erations and w as m ore
know n as Zu ska’s d isease) d oes not necessarily d evelop as frequ ent after m astectom y than breast-conserving su rgery.
a consequ ence of prim ary breast su rgical proced u res, bu t In ad d ition, serom a ap p eared to be significantly associated
this cond ition is notable for its high risk of com p lications w ith d evelop m ent of a su rgical site infection. Axillary sur-
follow ing su rgical treatm ent attem pts. This cond ition has gery lim ited to the sentinel lym p h nod e biopsy appears to
been associated w ith cigarette sm oking, and afflicted confer a low er risk of serom a form ation, bu t this proced ure
patients shou ld also be checked for tu berculosis as a factor is u su ally p erform ed w ithou t d rain insertion, and there-
in their recu rrent su perficial soft-tissue infections. Resec- fore, occasional p atients w ill requ ire su bsequ ent serom a
tion of the involved su bareolar d u ctal system (s) is fre- asp iration (31).
qu ently offered in an attem pt to break the cycle of repeated Several investigators have stu d ied strategies that m ight
abscesses, bu t these proced ures are frequ ently com p licated m inim ize serom a form ation in ord er to d ecrease the d u ra-
by w ou nd infections them selves and chronically d raining tion that d rainage catheters are need ed , or to obviate their
sinu s tracts. Som e patients w ith the m ost refractory cases need altogether. Talbot et al. (32) su bjected ninety consecu-
have even resorted to com p lete resection of the entire nip - tive breast cancer p atients u nd ergoing ALN D to (a) con-
ple-areolar com p lex, but this strategy should certainly be ventional, p rolonged closed su ction d rainage; (b) 2-d ay
reserved as a last-d itch effort. short-term d rainage; or (c) no d rainage. There w ere no d if-
ferences in infectiou s w ou nd com p lication rates betw een
Seroma the three grou p s, and at a minim u m follow -up of 1 year,
The rich lym p hatic d rainage of the breast from intram am - there w ere no d ifferences in lym p hed em a risk. In group 1,
mary lymp hatics to the axillary, supraclavicular, and inter- the d rain w as rem oved at a m ed ian of nearly 10 d ays, w ith
nal m am m ary nod al basins establishes the tend ency for 73% of cases requ iring su bsequ ent seroma aspiration. As
serom a form ation w ithin any closed sp ace that resu lts from exp ected , the short-term and no-d rain grou ps required
breast su rgery. Serom a occu rs at rates ranging from 3% to m ore frequ ent serom a asp irations (86% and 97%, respec-
85% after breast or axillary surgery (28). It has been p ro- tively). The m ean d u ration of su ction d rainage and / or
posed (29,30) that the low fibrinogen levels and net fibri- asp iration d rainages w as sim ilar for all three groups (25 to
nolytic activity w ithin lym phatic flu id collections accou nt 27 d ays). In all grou p s, flu id accu m u lation had m ostly
resolved by 4 w eeks, but in each group, there w ere a few tent resu lts, and it is therefore u nclear w hether the ad d ed
patients (approximately 16%) w ith prolonged d rainage last- exp ense of these agents is ju stified (29,46–48).
ing an ad d itional 2 to 3 w eeks. Sim ilar find ings have been
reported in old er stud ies (33,34). The number of d rains uti- Hematoma
lized and low - versus high-vacuu m su ction d o not appear Wid esp read u tilization of electrocau tery has largely d ra-
to affect the results achieved w ith d rainage catheters. m atically red u ced the incid ence of hem atom a form ation in
Shou ld er im m obilization w ith slings or sp ecial w rap s to breast su rgery, bu t this com p lication continu es to occur in
d ecrease serom a form ation has also been proposed , bu t 2% to 10% of cases. Som e low -volu m e hem atom a cases
this ap p roach carries the risk of p ossible long-term range of carry low m orbid ity, leaving the p atient w ith a m ore exten-
motion lim itations and m ay even increase the risk of lym - sive ecchym osis as the hem atom a is absorbed by ad jacent
phed em a (35). A reasonable alternative app roach end orsed soft tissu es. At the other end of the sp ectru m , large
by m ost breast su rgeons is to recom m end that patients sim - hem atom as can be qu ite p ainfu l becau se of rap id exp an-
ply lim it m otion at the shou ld er to abd u ction no greater sion throu gh the closed w ou nd sp ace, and these should be
than 90 , and active up per extrem ity physiotherap y is su rgically evacu ated , w ith aggressive w ou nd irrigation
d elayed u ntil after d rainage catheters are rem oved . This and reclosu re to op tim ize cosm esis.
strategy ap p ears to d ecrease serom a form ation com p ared An ongoing d ebate in breast su rgery has revolved
to early p hysiotherap y p rogram s and d oes not ad versely arou nd d efining the op tim al techniqu e for lu m pectom y
affect long-term range of m otion results (36,37). cavity closu re. Leaving the cavity op en to fill w ith serom a
The tissu e effects of electrocau tery are a w ell-recog- and closing the overlying skin w ith d eep d erm al sutures
nized risk factor for increased serom a form ation (29). Tw o and a final su bcu ticu lar layer has becom e a conventional
prospective clinical trials (38,39) have rand om ized breast w ou nd closu re strategy. This m ethod allow s for prom pt
cancer patients to u nd ergo su rgery w ith electrocautery ver- restoration of the breast contour through rapid filling of the
su s scalp el only and have confirm ed the low er incid ence of lu m p ectom y cavity by serom a; how ever, it requ ires meticu-
serom a form ation w ith the latter techniqu e. Few surgeons, lou s attention to insu ring hem ostasis along the lu m p ec-
how ever, are w illing to relinqu ish the convenience and tom y cavity w alls p rior to skin closu re. Many others
im proved hem ostasis associated w ith electrocau tery d is- therefore ad vocate u se of absorbable sutures to reapproxi-
section. Interestingly, Kontos et al. (40) cond ucted a m ate the d eep er lu m p ectom y tissu es, and this m aneuver
prospective stu d y involving 32 patients and fou nd no sig- has been rep orted to d ecrease the risk of hem atom a com -
nificant red uction in serom a form ation or w ou nd com pli- p lications (49). The d isad vantage of em p loying the d eep
cations betw een using harm onic scalp el versus trad itional cavity su tu res is the p otential for com p rom ising the final
electrocau tery d u ring breast cancer su rgery. cosm etic resu lt by altering the u nd erlying breast architec-
Classe et al. (41) reported successful use of axillary tu re and causing focal areas of retraction.
pad d ing in lieu of catheter d rains in 207 breast cancer The u se of a su p p ort brassiere in the p ostop erative
patients u nd ergoing ALN D in a stu d y from France, w ith p eriod w ill bolster efforts to sustain hem ostasis and
seroma formation in 22.2%. In contrast, the Memorial Sloan relieves tension on the skin closu re im posed by the w eight
Kettering Cancer Center cond ucted a clinical trial that ran- of the breast. This can be esp ecially im p ortant w ith large,
d omized 135 patients w ith ALN D to receive a compression p end u lou s breasts, w here blood vessels ru nning alongsid e
d ressing for 4 d ays versus stand ard w ound coverage (all the cavity can be avu lsed m echanically if the heavy breast
patients had conventional catheter d rainage as w ell) and is allow ed to su sp end u nsu p p orted . The p atient shou ld be
found no benefit from compression d ressings (42). Both encou raged to w ear the su p p ort brassiere d ay and night for
arms of this stud y had similar total d rainage volumes and several d ays.
d rainage catheter d urations, and the compression arm fur- Use of p articu lar m ed ications in the p eriop erative
thermore had increased seroma aspiration requirements p eriod has also been im p licated in the risk for bleed ing
(mean nu mber of aspirations 2.9 in the compression arm com p lication s. Asp irin -con tainin g p rod u cts an d non s-
compared to 1.8 in the stand ard d ressing arm; p 0.01). The teroid al an ti-inflam m atory d ru gs (N SAIDs) su ch as
cohort stud y rep orted by Kontos et al. (43) show ed that ibu p rofen have w ell-know n antip latelet activity, and these
pressu re d ressing w as an effective, cheap, and easy-to- med ications should be avoid ed for 1 to 2 w eeks prior to sur-
apply method for the red u ction of the time w ith d rains in gery (the lifespan of the affected platelets). Ketorolac has
situ after m od ified rad ical m astectom y (MRM), red u ced become a pop ular intravenou s su bstitute for opiate anal-
the number of patients d eveloping seromas and need for gesics d uring the postoperative period , but this agent is also
seroma aspirations. characterized as an NSAID and should be used cautiously
Chem ical m aneu vers to d ecrease serom a form ation in ord er to minimize risk of hematoma (50). In ad d ition,
have also been investigated . Application of tetracycline as a several over-the-counter m ed ications and su pplem ents that
sclerosing agent, has been ineffective (44). Bovine throm bin are w id ely u sed as “herbal supp lements” have recently
has been sim ilarly u nsu ccessfu l in this regard (45). Use of become recognized for contribu ting to a bleed ing d iathesis;
fibrin glu es, p atches, and / or sealants have ap peared p rom - these inclu d e ginseng, ginkgo biloba, and garlic (51,52).
ising, bu t clinical stu d ies in hum ans have yield ed inconsis- Usin g throm bop rop hylaxis, anticoagu lation m ed ication
preop eratively increases the chance of postop erative bleed - there w ere no d eaths. These investigators conclu d ed that
ing and hematoma. H ard y et al. (53) reported 0.4% rate of risk of VTE follow ing elective breast cancer su rgery is su ffi-
hem atom a form ation requ iring su rgical intervention after ciently low that rou tine anticoagu lant prophylaxis is
breast su rgery in patients receiving u nfractionated heparin u nnecessary and associated w ith excessive risk for postop-
as thromboprophylaxis. H ow ever, this rate w as 1.8% in erative bleed ing com p lications. Friss et al. (62) d em on-
patients receiving low -molecu lar-w eight heparin (LMWH ) strated that anti-VTE-d irected system ic therap ies w ith
as thromboprop hylaxis. In a retrospective stud y involving LMWH trip led the rate of w ou nd bru ising or hem atom a
1,055 p atients u nd ergoing core-need le biop sy, Somerville after breast su rgery w hen com p ared to thigh-long grad ed
et al. (54) show ed a statistically significant d ifference in com pression stockings w ith no red uction in the rate of
the percentage of ecchymoses betw een patients receiving throm boem bolic com p lications. Althou gh there are no
versu s not receiving anticoagu lation therap y. Bru ising p rosp ective rand om ized trials com p aring d ifferent m eth-
occu rred in 34% of anticoagulated w omen, w hereas bruis- od s of VTE p rop hylaxis in breast cancer p atients u nd ergo-
ing occurred in 26.5% of nonanticoagu lated w om en. In the ing p rim ary breast su rgery, a review by Patiar et al. (63)
same stud y, the d ifferences w ere not statistically significant ind icates that all patients should receive both grad u ated
for hem atoma formation or bruising w ith hematoma forma- com pression stockings and interm ittent pneum atic com -
tion. H ematoma occurred in 6% anticoagulated patients p ression d evices, w ith LMWH reserved for those at very
versus 4.2% patients in the control group. high risk, w hich they id entified as those w ith a history of
p rior VTE or throm bop hilia.
■ Venous thromboembolism complications Chronic Pain
specific to breast surgery A minority of breast cancer patients experience chronic inci-
Cancer is a know n risk factor for the d evelop ment of sional pain that can be quite debilitating and refractory to
venou s throm boem bolism (VTE), w hich inclu d es d eep - standard analgesics, lasting for several months to years post-
vein throm bosis and p ulmonary em bolism , and is associ- operatively. The exact etiology of this synd rome remains
ated w ith significant m orbid ity and m ortality (55–57). The obscure, although it is commonly assumed to be neuro-
resu lting hyp ercoagu lable state that occu rs in cancer pathic in nature. Frequently d escribed as a “burning,” “con-
patients is a com p lex event and includ es the exp ression of stricting,” or “lancing-type” of ache, it is reported among
tissu e factor and other p rocoagulants by tum or cells, acti- mastectomy as w ell as lumpectomy patients and is often
vation of vascu lar cells by tum or-d erived cytokines, and accompanied by ipsilateral upper extremity symptoms. The
ad hesive interaction betw een tum or and host cells (58). incid ence of this chronic pain synd rome is uncertain, but it
This risk m ay be com p ou nd ed by chem otherap y and hor- has been reported to afflict 20% to 30% of patients w ho are
mone therapy that is often part of the m ultid iscip linary specifically queried (64–68). Surprisingly, it has also been
treatm ent of breast cancer patients (59,60). There is an 8% reported to occur more commonly follow ing lumpectomy
and 17% rate of VTE for early and ad vanced stage breast compared to mastectomy cases (64,68). Risk factors identi-
cancer, resp ectively, reported in patients receiving fied w ith this synd rome includ e younger age, larger tumors,
chem otherap y (60). With increasing use of neoad ju vant rad iation therapy, chemotherapy, d epression, and poor cop-
chem otherap y and the increasing num ber of stage IV ing mechanism s (65,68,69). Fassoulaki et al. (70) reported
patients u nd ergoing prim ary breast surgery d u e to the higher intensity p ostop erative p ain, and higher analgesic
d u rable effects of system ic therapy, throm boem bolic p ro- requ irem ents are associated w ith chronic pain d evelop-
phylaxis shou ld be consid ered in these selected su bsets of m ent p ostop eratively. A p rosp ective stu d y by Poleshuck
patients u nd ergoing su rgery for breast cancer. et al. (71) show ed that clinical variables and severe acute
Breast cancer op erations for early-stage d isease (exclu d - p ain are risk factors for chronic p ain follow ing breast
ing cases that includ e im m ed iate reconstru ction) tend to be cancer su rgery, bu t p sychosocial d istress is not. They su g-
shorter in d u ration and are p erform ed in the am bu latory gested a hyp othesis that aggressive m anagem ent of acu te
setting, w ith relatively minim al postoperative d iscom fort p ostoperative pain may reduce chronic pain. The occasion-
w hen com p ared to intra-abd om inal or thoracic cancer ally intractable quality of this syndrome causes substantial
operations, thereby facilitating earlier p ostoperative am bu - frustration for both patients and surgeons. Fortunately,
lation, a significant factor in the red uction of p ostop erative recent successful management has been reported w ith use of
VTE events. A stu d y by And tbacka et al. (61) from the Uni- serotonin uptake inhibitors, such as the antid epressants
versity of Texas M.D. And erson Cancer Center evalu ated amitriptyline and venlafaxine (72).
the incid ence of VTE events in 3,898 breast cancer p atients
und ergoing 4,416 su rgical proced u res w ho w ere treated on ■ Complications specific to mastectomy procedures
clinical pathw ays w ith knee-length antiem bolic com pres-
sion stockings, calf-length interm ittent pneu m atic com - Incisional Dog-Ears
pression d evices, and early p ostoperative am bu lation. H eavyset p atients w ith thick axillary fat p ad s are esp ecially
They id entified seven p atients w ith a VTE w ithin 60 d ays p rone to being left w ith triangular or cone-shaped flaps of
of su rgery w ith a rate of 0.16% incid ence per p roced u re; red u nd ant skin and fatty tissue along the lateral asp ect of
their m astectom y incisions, com m only know n as “d og- 171 m onths), and these rates d eclined to 2% for patients
ears.” Frequ ently, the incisional d og-ear w ill not be read ily treated betw een 1994 and 1995 (XRT fractionation sched u le
app arent w hile the p atient is lying su pine on the operating 2.0 Gy 5 / w eek to 55 Gy, w ith m ed ian follow -u p of 75
room table, bu t w hen he/ she sits or stand s u pright p ostop - m onths). These find ings su ggest that extent of sid e effects
eratively, these u nsightly protrusions of axillary fat becom e is a fu nction of both follow -up d u ration and rad iation
obviou s and create significant d iscom fort to the p atient d elivery techniqu e. Sim ilarly, Meric et al. (76) reported
becau se they are irritating to the ipsilateral up per extrem - chronic breast sym p tom s in 9.9% of breast cancer patients
ity. Sim ilar to the infram am m ary fold p rior to m astectom y, treated by lu m p ectom y and rad iation from 1990 to 1992
these d og-ears can som etim es be the site for recu rrent can- and follow ed for at least 1 year p osttreatm ent.
d id al/ yeast infections. Arm lym p hed em a after breast su rgery has been stu d ied
N u m erou s su rgical approaches have been recom - by m any investigators. Tsai et al. (80) cond u cted a 2009
mend ed to either prevent or elim inate the d og-ear prob- m eta-analysis, w hich covered for 98 ind ep end ent stu d ies,
lem . One op tion is to bring the red u nd ant axillary tissu e and fou nd that the risk ratio for arm lym p hed em a w as
forw ard and create a “T” or “Y” configu ration at the lateral increased after m astectom y com p ared to lu m p ectom y. The
aspect of the transverse m astectom y incision (73). Alterna- estim ated relative risk w as rep orted 1.4.
tively, the red u nd ant axillary skin and fatty tissu e can be Moyer et al. (81) u tilized three-d imensional, d igital
resected either by elongating the stand ard ellip tical m astec- im aging and d ocu m ented a positive correlation betw een
tom y w ou nd or by u tilizing a broad “tear-d rop ” incision, p ercentage of breast p arenchym a excised (d u ring breast
w ith the p oint of the tear-d rop oriented med ially (74,75). conservation therap y) and asym m etry. The location of the
cancer, age of the p atient, and need for m u ltip le operations
d id not influ ence cosm etic resu lts. These w omen are cand i-
■ Complications specific to lumpectomy procedures d ates for variou s su rgical techniqu es w ith either im m ed i-
Breast fibrosis, breast lymphedema, arm lymphedema, breast ate or d elayed breast reconstru ction that can restore breast
asymmetry, and chronic/recurrent breast cellulitis: The p res- sym m etry. Op tions inclu d e local tissu e rearrangem ent,
ence of long-term ad verse sequ elae related to breast con- therap eu tic red u ction m am m ap lasty, and various flap
servation therap y for cancer is being increasingly reconstru ction p roced u res. Each techniqu e has ad vantages
acknow led ged and reported (76,77). These com plications and d isad vantages. Im med iate reconstru ction (at the tim e
are second ary to the com bined tissue effects of su rgery and of breast conservation su rgery) is p referred over d elayed
rad iation therap y. Collette et al. (78) evalu ated 10-year fol- reconstru ction. Patients tend to be satisfied w ith the cos-
low -u p of EORTC trial 22881–10882 in 5,178 conservatively m etic ou tcom e of these p roced u res, bu t thorou gh p atient
treated early breast cancer p atients and show ed that a counseling and preoperative or im m ed iate p lanning is crit-
16-Gy boost d ose significantly im proved local control, bu t ical to a good result.
increased the risk of breast fibrosis. Risk of fibrosis signifi- Recu rrent ep isod es of breast cellu litis occu rring sev-
cantly increased (p 0.01) w ith increasing m axim um w hole eral m onths to years after lu m p ectom y and / or breast
breast irrad iation d ose and w ith concom itant chem oth er- rad iation therap y is rep orted to afflict 5% of p atients,
ap y, bu t w as ind ep en d ent of age. In the boost arm of th e bu t this u nu su al and d elayed com p lication cau ses signifi-
stu d y, the risk fu rther increased if p atients had p ostop er- cant concern becau se of the need to ru le ou t an inflam m a-
ative breast ed em a or hem atom a, bu t it d ecreased if tory breast cancer recu rrence (82–86). This cond ition can
w h ole breast rad iation w as given w ith m ore th an 6 MV p resent as a m yriad of scenarios: acu tely inflam ed serom a
p h oton s. The Eu rop ean Organ ization for Research and form ation; localized m astitis; or d iffu se breast p ain and
Treatm ent and the Rad iation Therap y Oncology Grou p sw elling. Rep eat breast im aging is ind icated to look for
have p rop osed that late effects of breast conservation ther- p arenchym al featu res su ggesting recu rrence, su ch as an
ap y (inclu d ing breast ed em a, fibrosis, and atrop hy/ retrac- u nd erlying sp ecu lated m ass, calcifications, etc., and if pres-
tion) be grad ed accord ing to the Late Effects of N orm al ent, an im age-gu id ed biop sy shou ld be p u rsu ed . Otherwise
Tissu e-Su bjective, Objective, Managem en t, and Analytic benign-appearing cases that are refractory to a standard
(LEN T-SOMA) scales (79). The LEN T-SOMA system strati- cou rse of antibiotics shou ld u nd ergo p u nch biop sy for
fies breast sym p tom s on the basis of p ain magnitu d e as further evaluation. Occasionally, patients w ho ultimately
reported by the p atient, m easu rable d ifferences in breast request mastectomy because of intractable pain and inflam -
appearance, intervention requirem ents for control of p ain m ation are encou ntered .
and / or lym p hed em a, and presence of im age-d ocum ented The cau se of d elayed breast ed em a and cellu litis is
breast sequ elae (e.g., p hotos, m am m ograp hy, CT/ MRI, incom p letely u nd erstood , bu t is p resu med to be related to
etc.). lym phatic obstruction affecting intram am m ary d rainage.
Using the LEN T-SOMA fou r-p oint grad ing system , Risk factors for this cond ition includ e history of early post-
Fehlau er et al. (77) reported grad e 3–4 toxicity in 4% to 18% op erative com p lications su ch as hematom a and serom a;
of breast cancer p atients treated betw een 1983 and 1984 u p p er extrem ity lym p hed em a; and large-volu m e lu m pec-
(external beam rad iotherapy [XRT] fractionation sched u le tomies (83). Most cases have follow ed resection of upper
2.5 Gy 4 / w eek to 60 Gy, w ith m ed ian follow -u p of ou ter qu ad rant tu m ors. Rarely is a cau sative bacterial
pathogen id entified in these cases, bu t the conventional conform ance). Of the 54 p atients w ho had a balloon
management inclu d es antibiotic coverage for skin flora inserted , 57% exp erienced overlying skin erythem a and
nonetheless. Ind elicato et al. (27) cond ucted a retrosp ective tw o p atients d evelop ed w ou nd infections, inclu d ing one
stu d y involving 601 patients w ith breast cancer u nd ergo- abscess.
ing breast conservation therapy and reported an overall
incid ence of 8% for d elayed . Med ian tim e of onset w as 226 Breast Conservation Therapy-Related Angiosarcoma
d ays. More than 90% of all effected patients w ere treated Review ed in d etail by Monroe et al. (89), angiosarcom as of
em p irically w ith antibiotics. Tw enty-tw o percent had the breast follow ing lu m pectom y and XRT for breast cancer
recurrent episod es of d elayed breast cellulitis (DBC) and 4% are very rare, but are being reported w ith increasing infre-
und erw ent mastectomy for intractable breast pain related to quency. These second ary angiosarcomas are to be d istin-
DBC. They conclud ed DBC is primarily related to a bacter- guished from primary breast angiosarcomas, w hich occur
ial infection in the setting of im p aired lym phatic d rainage in relatively younger-aged w omen and w hich have no w ell-
and may ap pear months after completion of rad iotherapy. d efined risk factors. Second ary angiosarcom as occur 4 to 10
The d evelopment of this complication d oes not appear to years after p rimary breast cancer treatment (89–91). H od g-
carry any cancer-related prognostic significance. son et al. (92) cond ucted a retrospective stu d y of 70 w omen
Lumpectomy and Brachytherapy-Related Complications w ith breast angiosarcoma and reported the mean time to
d iagnosis of the angiosarcom a as 5.2 years after breast can-
Several breast p rogram s are cu rrently exp loring strategies cer irrad iation. H e conclud ed second ary breast angiosar-
of p artial breast irrad iation that allow for shortening of the coma patients present w ith more ad vanced d isease and
conventional 5- to 6-w eek external beam program . One surgical resection is the prim ary therapy. Lym phed em a-
su ch strategy involves insertion of a balloon-typ e catheter related extrem ity angiosarcom a (Stew art–Treves synd rom e,
(the Mam m oSite ap plicator) into the lu m pectom y cavity d iscu ssed below ) has a longer latency p eriod from tim e of
for d elivery of brachytherap y. This d evice is typ ically breast cancer treatm ent. Furthermore, the occurrence of
inserted in the operating room at the tim e of lu m pectom y, breast angiosarcom as in the irrad iated field , coupled w ith
w ith the exp ectation that m argin control w ill be achieved ; the im plications for genetic pred isposition to rad iation-
if this is not the case, then ad d itional surgery and a second ind uced tumorigenesis (e.g., ataxia-telangiectasia) have
im p lantation is required . While investigations of the long- p rompted sp eculation that these lesions have a d ifferent eti-
term efficacy of these accelerated breast irrad iation pro- ology compared to Stew art–Treves synd rome. Med ian sur-
grams are being cond ucted , experience w ith catheter-related vival, how ever, is sim ilarly poor, at 1 to 3 years (89).
risks is accumulating. CT imaging is subsequently per-
form ed to ensure ad equate balloon placement, as d efined by
a minimum applicator–skin distance of 5 mm, and appropri- ■ Complications specific to diagnostic
ate conformance, w ith uniform contact between the balloon open biopsy procedures
and lumpectomy walls. Optimal positioning can be chal-
lenging, but is essential for delivery of therapy w ith minimal Sampling Error
risk of local complications. The prim ary potential risk sp ecifically associated w ith a
Breast rad iation therap y (esp ecially for left-sid ed d is- d iagnostic op en biop sy is related to m issing a cancerou s
ease) has been im plicated in risk for card iac d isease. A ret- lesion and resecting ad jacent fibrocystic tissu e, thereby
rosp ective stu d y by Gu tt et al. (87) in 2008 evalu ated m isd iagnosing the p atient. This com p lication exists w ith
card iac m orbid ity and m ortality after breast conservation p alp able m asses as w ell as w ith screen-d etected nonpalpa-
treatm ent in p atients w ith early staged breast cancer and ble lesions.
preexisting card iac d isease. These investigators fou nd a The risk of m isd iagnosis w ith p alp able breast m asses
higher incid ence of card iac d eath in patients w ith left can be m inim ized by com p lete p reop erative breast im ag-
breast cancer. This find ing w as presum ed to be related to ing, inclu d ing m am m ograp hy and u ltrasonograp hy. Palpa-
second ary card iac effects of irrad iation. Whole breast rad i- ble lesions that have a su spiciou s-appearing im aging
ation techniqu es and tangent/ field planning has evolved correlate shou ld have an initial attem p t at p ercu taneou s
substantially over the past several d ecad es, and extent of core-need le biop sy to establish a d iagnosis. If m alignancy
card iac effects in contem porary breast cancer treatm ent is is confirm ed , then cancer-d irected m anagem ent options
therefore less clear. It is likely that u se of CT p lanning and can be p rom p tly ad d ressed . N eoad ju vant chem otherapy is
other ad vances has resu lted in m inim ized scatter effects to one su ch op tion for eligible p atients w hile the patient has
intrathoracic organs, rend ering ad verse im p act to be p ri- m easu rable d isease in the breast, and the p otential benefits
marily experienced by patients w ith und erlying card iac of tu m or d ow nstaging to im p rove breast conservation
and / or p u lm onary d isease. therap y success as w ell as to monitor chemosensitivity then
Resu lts from a p rospective, m u lticenter stu d y of the remain available to the patient (93). If the percutaneous
Mam m oSite d evice (88) revealed that of seventy p atients biopsy w as performed freehand and returns nond iagnostic,
enrolled , 21 (30%) cou ld not com plete the stu d y becau se of an image-guid ed (either by ultrasound or stereotactic/ mam-
lum p ectom y-related issu es (cavity size, skin sp acing, or mographic) need le biopsy can be attem p ted . Alternatively
(and if resou rces are available), the percu taneous biop sy rary breast p rogram s. With this algorithm , the likelihood of
may be performed w ith im age gu id ance as the initial m issing the target shou ld occu r in 5% of cases. Risk fac-
maneu ver in ord er to im prove the d iagnostic accu racy. tors for a sam p ling error com p lication d esp ite these p re-
If the p alp able lesion d oes not have an im aging corre- cau tions inclu d e su bop tim al w ire localization, localizing
late, or if need le biopsy strategies are unavailable, then a w ire m igration betw een the tim e of insertion and the tim e
d iagnostic op en biopsy m u st be p erform ed . Sam p ling of su rgical resection, and m igration of a p reviously
errors w ith these p roced ures are uncom m on, but p atients inserted clip that w as intend ed to m ark the site of a prior
w ith extensive fibrocystic changes can be challenging, core-need le biop sy. When a sam p ling error is recognized
especially in cases w here the lesion w as a self-d etected intraop eratively, based on sp ecim en im aging, it is qu ite d if-
mass that is less d om inant on clinical exam ination. In these ficu lt to reorient the breast anatom y intraop eratively w ith-
cases, the breast should be assessed and m arked ju st p rior ou t the localizing w ire. In this circu m stance, it is p rud ent to
to surgery by the su rgeon and patient together, but intraop - resist m u ltip le attem p ts at “blind ” biop sies, as the likeli-
erative su rgical ju d gm ent remains critical, and any su sp i- hood of su ccess is low and the ad d itional tissu e resections
ciou s m asses id entified w ithin the open breast w ound w ill com p rom ise cosm esis. The p atient shou ld be inform ed
shou ld be biop sied and oriented ap p rop riately. of the failed p roced u re, and rep eat im aging should be
The risk of sam p ling error w ith nonp alp able breast rep eated 2 to 4 w eeks p ostop eratively, w ith plans for
lesions is greater. Establishing a d iagnosis for clinically another w ire localization m ad e accord ingly.
occu lt lesions that are id entified by m am m ogram or A rare com p lication associated w ith w ire localization
u ltrasou nd necessarily d ep end s on im age gu id ance. As breast su rgery is a retained w ire fragm ent that results from
noted earlier, th ere are ad vantages to p roceed ing w ith an inad vertent transection of the localization w ire d u ring exci-
im age-gu id ed p ercu taneou s need le biop sy as the initial sional biop sy. Montrey et al. (96) rep orted on 10 patients
d iagnostic strategy. Can cer p atients w hose d iagn osis has id entified over a 2-year p eriod at a single institu tion w ith
been m ad e via n eed le biop sy are m ore likely to have su c- retained w ire fragm ents that w ere p resent over intervals
cessfu l breast conservation therap y and requ ire few er ranging betw een 1.5 and 11 years. One p atient experienced
reexcisions for m argin control com p ared to p atients w ho breast p ain that resolved w ith rem oval of the fragm ent and
u nd ergo an initial op en biop sy for d iagnostic p u rp oses there w ere no rep orts of infection or other com p lications. In
(94). A core-need le biop sy is p referable com p ared to a this sam e stu d y, Montrey et al. d eterm ined that the fre-
fine-need le asp iration biop sy becau se of the larger tissu e qu ency of retained w ire w as 0.2%. Althou gh the natu ral
yield , w hich can d istingu ish in situ from invasive archi- history of a retained w ire fragm ent is relatively benign,
tectu re, and also becau se the sam p ling error w ith a fine- w ith the increasing u se of breast MRI and incom p atibility
need le asp iration biop sy can be as high as 30%, of m any localization w ires w ith MRI in ad d ition to the scat-
com p ared to only 5% to 10% w ith a core need le. If the tar- ter artifact the retained foreign bod y can cau se, the clinical
geted lesion is sm all and m ay be com p letely resected significance of retained w ires m ay becom e m ore p roblem -
w ithin th e core sp ecim ens, then a rad iop aqu e clip shou ld atic for the clinician.
be left in p lace to facilitate su bsequ ent localization in case
su rgery is requ ired . ■ Complications related to axillary
When high-risk lesions such as atypical hyperp lasia,
staging procedures
rad ial scar, or lobu lar carcinom a in situ are id entified on
core-need le biop sy, a follow -up open su rgical biop sy The axillary nod al status rem ains the m ost pow erfu l prog-
should be p erform ed . The sam pling error rates associated nostic featu re in staging p atients w ith invasive breast can-
w ith these find ings are su bstantial, and 10% to 40% are cer. Su rgical staging of the axilla is necessary for the
upstaged to cancer on su bsequent open biopsy (95). m ajority of new ly d iagnosed p atients, as cu rrently avail-
Op en su rgical biopsies of nonpalpable, im age-d etected able im aging m od alities can easily m iss sm all nod al m etas-
breast lesions requ ire im age-guid ed w ire localization. The tases. The conventional level I/ II ALN D is the gold
localizing w ire can be inserted u nd er either u ltrasou nd or stand ard m eans of evalu ating the axilla, bu t lym phatic
mam m ograp hic gu id ance, d ep end ing on w hich m od ality m ap p ing and sentinel lym p h nod e biop sy have recently
best im ages the abnorm al lesion. MRI-gu id ed w ire local- em erged as a viable alternative strategy for accu rately
ization technology is available in som e centers as w ell. Past d eterm ining the nod al statu s. Each of these staging p roce-
strategies for localization have inclu d ed external skin d u res is associated w ith risks for variou s com p lications
markings and preoperative injection of d ye into the vicinity and w ill be d iscu ssed sep arately.
of the lesion, bu t have been largely aband oned becau se of
higher sam p ling error rates. Insertion of a hooked w ire, Complications Associated with ALND
w ith tw o-view confirm atory m am m ograp hy of the w ire The level I/ II ALN D is the conventionally accepted staging
position in relation to the abnorm al lesion, follow ed by p roced u re. Rand om axillary sam p ling p roced u res and
mam m ographic (and / or ultrasonograp hic) im aging of the ALN D lim ited to level I can m iss m etastases in 20% to 25%
biopsy sp ecim en to d ocum ent inclusion of the suspiciou s of cases. A level III d issection is generally consid ered
target, is the rou tine m ost w id ely emp loyed in contem p o- u nn ecessary (u n less th ere is grossly ap p arent d isease
present in the axillary apex) becau se skip m etastases to association betw een p ostm astectom y lym p hed em a and the
level III only occu r in 2% to 3% of cases. The presence of an onset of this m alignancy, typ ically ap p earing as blu ish-red -
“axillary arch” has been proposed as an anatom ic variant d ish m acu lar lesions or nod u les on the skin of the ip silat-
that can increase the risk of sam p ling error w hen a stan- eral u p p er extrem ity. This d isease generally d evelops
d ard level I and II ALN D is p erform ed (97). The axillary ap p roxim ately 10 years after breast cancer treatm ent, and it
arch is form ed by an aberrant segm ent of latissim u s d orsi is usu ally (but not alw ays) seen in patients w hose lym -
mu scle that extend s tow ard the pectoralis. If the axillary p hed em a risk has been am p lified by regional irrad iation in
d issection d oes not encom pass the lym phatic tissue lateral ad d ition to ALN D. Treatm ent strategies have includ ed
to these fibers, then significant nod al tissu e can be m issed ; w id e local excision, am p u tation, chem otherap y, and / or
failu re to appreciate this anatom ic variant has been im pli- rad iation, w ith d isap p ointing resu lts. Most patients suc-
cated as a cau se for subsequ ent axillary recurrence (98). cu m b to hem atogenously d issem inated m etastases to lung
Upper extrem ity lym phed em a is the com plication that and visceral organ, w ith a m ed ian su rvival of approxi-
has generated the m ost concern follow ing ALN D becau se it m ately 2 years.
is a lifelong risk follow ing the p roced ure and quite refrac- The axillary d issection su rgical bed exp oses the axil-
tory to treatm ent w hen it occu rs. Lym phed em a has been lary vein, thoracod orsal, long thoracic (“nerve of Bell”),
rep orted to d evelop in 13% to 27% of patients w ith breast and intercostobrachial nerves, as w ell as the neu rovascu -
cancer (31,99–102), but d etection rates vary based on how lar bu nd le to the p ectoralis m u scu latu re. The intercosto-
closely patients are follow ed and d uration of follow -up. brachial nerves are rou tinely sacrificed d u ring a
Risk of lym phed em a is increased in p atients after a higher- conventional ALN D as they cou rse d irectly throu gh the
level axillary d issection com pared to less extensive su rgery, nod al tissu e en rou te to the skin of the axilla and u p p er
bu t has been rep orted to occu r even after axillary su rgery inner arm , leaving p atients w ith sensory d eficits in this
lim ited to the sentinel lym p h nod es (31). Other risk factors d istribu tion. Attem p ts to p reserve these nerves can resu lt
inclu d e obesity and regional rad iation therapy. Patients can in d am age that leaves the p atient w ith chronic neu ro-
minim ize risk of lym phed em a by p articipating in an p athic p ain of the involved skin. The axillary vein is at
aggressive and regu lated physical therapy p rogram , and risk for hem orrhagic com p lications as a consequ ence of
onset of this p roblem is aggravated by u p p er extrem ity d irect inju ry, or throm bosis second ary to traction and / or
trau m a or infection. com p ression. The axillary artery and brachial p lexu s are
One techniqu e cu rrently being investigated to m ini- relatively p rotected from intraop erative d am age becau se
m ize lym p hed em a after axillary su rgery is axillary of their d eep er and m ore su p erior location. The thora-
reverse m ap p ing (ARM) w here blu e d ye is injected intra- cod orsal neu rovascu lar bu nd le, w hich cou rses along the
d erm ally or su bcu taneou sly in the ip silateral arm to id en- inner asp ect of the latissim u s d orsi m u scle, shou ld be
tify the d raining arm lym p hatics w ithin the axilla. Breast com p letely exp osed and p reserved intact, u nless there is
sentinel lym p h nod e biop sy is p erform ed u sing injection gross encasem ent by nod al m etastases. Sacrifice of these
of technetiu m su lfu r colloid . Du ring axillary d issection, stru ctu res w ill d enervate the latissim u s (leaving the
w hich inclu d es both sentinel lym p h nod e and ALN D, p atient w ith w eakness of internal rotation and shou ld er
blu e channels and lym p h nod es are p reserved in vivo. In abd u ction) and elim inates availability of the thoracod or-
the p ilot stu d y of this techniqu e p erform ed by Thom p son sal vessels for p ossible fu tu re u se in conju nction w ith
et al. (103), the su ccess rate of id entifying either blu e lym - m icrovascular anastom oses for free flap reconstructions.
p hatic channels or blu e lym p h nod es w ithin the axilla w as Disru p tion of the long thoracic nerve resu lts in loss of ser-
61%, and after 8 m onths of follow -u p , none of the p atients ratu s anterior fu nction, and a “w inged scap u la” d eform ity,
w ho had ARM blu e lym p hatics id entified and p reserved w ith an u nsightly p osterior shou ld er bony p rotru sion.
have d evelop ed arm lym p hed em a (103). In ad d ition, When the m ed ial and lateral p ectoral nerves are transected ,
there w as 100% nonconcord ance betw een the breast and d enervation atrop hy of the p ectoral m u scles w ill eventu -
arm lym p h nod es, i.e., none of the blu e nod es (p resu m - ally becom e ap p arent and can com p rom ise the patient’s
ably the nod es resp onsible for extrem ity lym p hatic cosm etic resu lt substantially.
d rainage) had evid ence of technetiu m colloid nor d id any Axillary w ebs are band s of scar tissue that d evelop after
of the rad ioactive nod es (p resu m ably the nod es resp onsi- ALN D in 10% of cases, and they are read ily ap parent as
ble for breast and tu m or lym p hatic d rainage) have evi- cord like stru ctures coursing from the su rgical bed tow ard
d ence of blu e d ye. Though prelim inary d ata are prom ising, the forearm and occasionally reaching the thu m b (107).
fu rther stud ies and longer follow -u p is need ed to ensure They cau se significant tightness and lim itation of m otion,
feasibility of this novel techniqu e to m inim ize the risk of bu t in m ost cases resolve w ithin a few m onths. Physical
lym phed em a. therap y and m assage are frequ ently help fu l in alleviating
One of the m ost feared long-term sequ elae of chronic sym p tom s.
lym phed em a is the d evelopm ent of upp er extrem ity One final rare com p lication of the ALN D is chyle leak
angiosarcom a (104,105). This cond ition is also know n as (108) som etim es rep u ted to be second ary to thoracic d u ct
Stew art–Treves synd rome (106), nam ed for the investiga- inju ry. Recently, octreotid e has been recom m end ed to con-
tors w ho first rep orted a series of cases d em onstrating the trol extensive lym p horrhea (109).
Complications Associated with Lymphatic Mapping crim inate focal u p take by the sentinel nod e; likelihood of
and Sentinel Lymph Node Biopsy m issing the tru e sentinel nod e and obtaining a false-nega-
Krag et al. (110), in 1993, u tilizin g rad iolabeled isotop e, tive resu lt is then increased . In contrast, m ed ially located
and Giu liano et al. (111), in 1994, u tilizin g blu e d ye, in i- tu m ors have been associated w ith risk of m ap p ing failu re
tially rep orted abou t lym p h atic m ap p in g an d sen tin el becau se of the increased likelihood of p rim ary lym p hatic
lym p h n od e biop sy for p atients w ith breast cancer. There d rainage to nonaxillary sites. Other rep orts (118) have
w as p rom p t recogn ition that this techn ology rep resen ted fou nd no relationship betw een tu m or location and sen-
a p rom ising strategy to id entify nod e-negative p atients tinel nod e accu racy. An ad d itional factor im p licated in
and sp are them the m orbid ity of a con ven tional ALN D. m ap p ing inaccu racy is size of the p rim ary tu m or; w ith
Since these p ioneering stu d ies w ere p u blished , d ozens larger size lesions, there is risk of tu m or em bolization
of oth er in vestigators h ave rep orted th eir exp erien ces cau sing obstru cted lym p hatic vessels, thereby altering the
w ith lym p h atic m ap p ing and sentinel lym p h n od e p athw ay that a m ap p ing agent w ou ld follow. While early
biop sy in con ju nction w ith a com p letion ALN D in ord er stu d ies (119) d id su ggest a correlation betw een breast
to d efin e th e accu racy an d op tim al tech n iqu e for p er- tu m or size and risk of a false-negative sentinel lym p h
form in g th is p roced u re. A m eta-analysis of these typ es of nod e biop sy, m ore recent stu d ies have ind icated no asso-
stu d ies (112) p resented at the Am erican Society of Clini- ciation (120–122).
cal On cology 2002 an n u al sym p osiu m revealed overall Many of the p otential p itfalls in lym p h atic m ap p ing
id en tification rate of 96% and overall false-negative rate p roced u res h ave been obviated by the d evelop m ent of
of 8.4%; th is an alysis in clu d ed d ata from 69 stu d ies new er m ap p ing techn iqu es, su ch as su bareolar in jection s
involving 10,454 p atients. Low er-volu m e stu d ies, early of th e m ap p ing agen t (123–125). Th e basis for this strat-
p hase of the learning cu rve w ith lym p hatic m ap p ing egy is the em bryologic d evelop m ent of the breast and its
tech n ology, an d u se of a sin gle m ap p in g agen t (blu e d ye lym p hatic d rainage system , w hich begins as the centrally
or isotop e versu s u se of both) w ere id en tified as risk fac- located nip p le bu d , follow ed by rad ial extension p erip h-
tors for th e com p lication s of eith er a failed m ap p in g p ro- erally. This lead s to the concep t that each breast has p ri-
ced u re or obtain in g a false-n egative sen tin el lym p h n od e m ary d rain age to a d iscrete clu ster of sentinel lym p h
resu lt. nod es, as op p osed to sep arate d rain age p ath w ays for d if-
Table 44.2 su m m arizes the results of stu d ies that have ferent areas of th e breast. Th is m od el fu rth er op ens th e
evaluated specific cau ses for inability to id entify the sen- d oor for im p rovin g th e ease of lym p hatic m ap p in g in
tinel lym p h nod e and featu res that p red ict for a greater risk cases of m u lticentric breast cancer, w hich p reviou sly had
of id entifying a falsely negative result. Sim ilar to the m eta- been consid ered a contraind ication to sentinel nod e
analysis find ings, inexp erience w ith lym phatic m ap p ing biop sy.
and u se of a single m apping agent rather than tw o agents Recen t stu d ies of lym p h atic m ap p ing in p atients w ith
are rep eated ly im p licated w ith u nsuccessful sentinel m u ltifocal and / or m u lticentric d isease h ave d em on -
lym ph nod e biop sies. The steep learning cu rve and the strated that sentinel lym p h nod e biop sy is accu rate in
benefits of d u al versu s single m apping agents are exp lored th is settin g (126–130). From th ese stu d ies, it ap p ears
and presented in d etail by Cox et al. (113) and Derossis th at th e sen tin el n od e can be id en tified by in jection tar-
et al. (114), resp ectively. geting the d ifferent breast tu m ors or by u se of the su bareo-
The original stu d ies of sentinel lym p h nod e biop sy lar techniqu e.
involved intrap arenchym al, p eritu m oral injections of the Other com p lications that have been rep orted follow ing
m ap p ing agent(s), since the goal is to rep licate the p ath- a sentinel lym p h nod e biop sy are the sam e as those that are
w ay traversed by tu m or cells along intram am m ary lym - associated w ith ALN D, inclu d ing seroma, lym p hed em a,
p hatic channels en rou te to the sentinel nod e. If the axillary w eb form ation, and neu rosensory d istu rbances,
m ap p ing p roced u re is being p erform ed after a p rior exci- bu t the m agnitu d e of risk is low er. Data on long-term fol-
sional biop sy, there is a risk of inad vertent injection into low -u p of p atients w ho have u nd ergone sentinel lym ph
the biop sy cavity and the m ap p ing agent m ay not reach nod e biopsy alone are now revealing ad verse sequelae
the nod al basin. As exp erience w ith lym p hatic m ap p ing occu rring in 5% of cases (31,101,131).
grew, these technical failu res d eclined and investigators Risk of allergic reactions to the blu e d ye for m ap p ing
have sp ecifically d ocu m ented the ability to reliably id en- p roced u res m u st be consid ered . Table 44.3 d em onstrates
tify the sentinel lym p h nod e in the setting of p rior exci- rep orted series, involving both isosu lfan blu e and p atent
sional biop sy (115,116). Injection of skin overlying the blu e d ye. Within a few m inu tes to an hou r follow ing blu e
tu m or site fu rther im p roves sentinel nod e id entification d ye injection, u p to 2% of p atients m ay exp erience su d d en
rates becau se of exu berate u p take by d erm al lym p hatics hem od ynam ic instability and other sequ elae of intraop er-
(117). With increasing age, lym p h nod es can becom e fatty- ative anap hylaxis. Desp ite the d ram atic p resentation,
rep laced and d ifficu lt to recognize, also contribu ting to a these ep isod es are u su ally read ily resp onsive to su p p ort-
failed id entification. For tu m ors located in the u p p er, ive care, w hich inclu d es d iscontinu ation of the gaseou s
ou ter qu ad rant of the breast, extensive backgrou nd anesthetics, 100% oxygen, aggressive flu id resu scitation,
rad ioactivity (shine-throu gh) im p airs the ability to d is- and p ressor su p p ort. In m ost cases, the anesthesia and
Table 4 4 .2 Se le ct e d s t u d ie s r e p or t in g r is k fa ct o r s fo r fa ile d lym p h a t ic m a p p in g a n d /or fa ls e - n e g a t ive s e n t in e l lym p h
n o d e (SLN ) b io p s y
Factors Associated with SLN Nonidentification
Single
Tumor Single Tumor Versus
Total SLN ID SLN FN Location Prior Versus Dual Larger Location Older Prior Dual Larger
No. of Rate Rate Learning (Medial Older Excisional Mapping Size Learning (UOQ Age Excisional Mapping Size
Study Cases (%) (%) Curve Worse) Age Biopsy Agent Tumor Curve Worse) Patient Biopsy Agent Tumor
Canavese (146) 212 97.1 6.5 No NR NR NR Yes No No NR NR NR No Yes
Albertini et al. 62 92 0 NR NR NR NAa Yes NR No No No No No No
(147)
McMasters 806 88 7.2 No No Yes No Yes No No Yes No No Yes No
et al. (148)
Veronesi et al. 163 98 4.7 No No No No NA (Tc Yes No Yes No No NA Yes
(119) only used)
Veronesi et al. 376 98.7 6.7 No No NR NR No No No No No NR No No
(120)
Cox et al. (149) 465 94.4 UK Yes NR NR No Yes NR Yes NR NR NR NR NR
Giuliano et al. 174 65.5 8.1 Yes NR NR NR NA (dye NR Yes NR NR NR NR NR
(111) only used)
Bedrosian et al. 104b 99 3.3 NR NR NR NR NR No NR NR NR NR NR No
(121)
Haigh et al. 284c 81.0 3.2 NR No NR No NR No Yes No NR No NR No
(115)
Wong et al. 2,206d 92.5 8.0 NR No NR No NR Yes NR No NR No NR No
(116)
Krag et al. (150) 443 93 12.8 NR Yes Yes Yes NA(isotope- No NR Yes No No NA No
only used) (isotope-
only used)
O’Hea et al. 59 93 15 NR No NR No Yes No Yes No NR No No Yes
(151)
Guenther (152) 260 81.9 NRe Yes Yes NR No NA (dye NAe NAe NAe NAe NAe NAe NAe
only used)
a
Patients with prior excisional biopsy excluded from study.
b
All T2 and T3 tumors.
c
Including 181 lymphatic mapping cases with prior excisional biopsy.
d
Medial location worse.
e
Analyses limited to 47 patients with unsuccessful mapping procedures
FN, false negative; ID, identification; NA, not applicable; NR, not reported.
Table 4 4 .3 Select ed st u d ies of a ller gic r ea ct ion s t o blu e dye in br ea st ca n cer ca ses
Study, Year Blue Dye Type No. of Cases (Type) Incidence (%) No. of Second Reactions
Lyew et al., 2000 (153) Isosulfan blue 1 (anaphylactic) NR No
Mullan et al., 2001 (154) Patent blue
Cimmino et al., 2001 (135) Isosulfan blue 5 (3 anaphylactica; 2 No
2 blue urticaria)
Albo et al., 2001 (155) Isosulfan blue 7 (all anaphylactic) 1.1 2/7 (%)
Montgomery et al., 2002 (156) Isosulfan blue 39 (27 blue hives; 1.6 NR
12 anaphylactic)
Efron et al., 2002 (133) Isosulfan blue 1 (anaphylactic) NR No
Laurie et al., 2002 (132) Isosulfan blue 2 (anaphylactic) NR No
Stefanutto, 2002 (157) Isosulfan blue 1 (anaphylactic) NR No
Crivellaro et al., 2003 (158) Patent blue 1 (anaphylactic) NR No
Sprung et al., 2003 (159) Isosulfan blue 1 (anaphylactic) NR Possibly; protracted
hypotension noted
a
Series includes two cases of lymphatic mapping performed for breast cancer.
su rgical p roced u re have been resu m ed and com p leted are contraind icated d u ring p regnancy becau se the risk of
u neventfu lly after the p atient has been stabilized . Som e teratogenicity is u nknow n.
su rgeons, how ever, have elected to abort the su rgical p ro-
ced u re (132) and resched u le the m ap p ing w ithou t blu e ■ Complications specific to immediate
d ye, and in one rep orted case (133), a p lanned lu m p ec- breast reconstruction
tom y w as converted to a m astectom y so that the allergen
focu s w ou ld be com p letely resected . Many other p atients A d etailed d iscu ssion of breast reconstru ction op tions and
have p roceed ed to u nd ergo su ccessfu l lu m p ectom ies, bu t their com plication risks is beyond the scope of this chapter,
they shou ld be m onitored closely for 24 hou rs becau se bu t a few p articu lar issu es w arrant m ention. The risk of
continu ed u p take of the blu e d ye from skin and soft tissu e w ound com plications associated w ith any type of recon-
can resu lt in p rotracted or d elayed second ary (bip hasic) stru ction w ill be increased by sm oking history, obesity, and
reactions. chest w all irrad iation.
“Blu e u rticaria,” a less severe form of blu e d ye allergy
characterized by blu e-tinged hives, is another pattern that Skin-Sparing Mastectomy
has been rep orted (134,135). There is no correlation w ith The skin-sp aring m astectom y techniqu e has becom e
p ast allergy history, and p reoperative skin testing is u nreli- increasingly p op u lar as a m ean s of im p rovin g the cos-
able in id entifying highest-risk patients. One hypothesis is m etic resu lts achieved by IBR, bu t the su rgeon shou ld
that m any ind ivid uals have prior sensitization from expo- take p articu lar cau tion in raising the elon gated skin flap s
sure to ind u strial d yes in cosm etics, textiles, d etergents, etc. so that risk of retained breast tissu e and increased local
Rou tine p rem ed ication of all m ap p ing cases w ith steroid s, recu rren ce rates is m inim ized . Wh en the oncologic p rin-
antihistam ines, and / or histam ine recep tor blockad e has cip les of th e m astectom y are u p held , breast cancer ou t-
been p rop osed , bu t the ad d ed expense and risks of this com e is equ ivalent for p atien ts u nd ergoin g skin -sp aring
ap proach for a low -incid ence allergic reaction has not been and conventional m astectom y w ith IBR (137–139). Local-
d ocum ented . Know n allergy to triphenylm ethane is a con- ized w ou n d p roblem s su ch as m in or infections, focal
traind ication to blu e d ye u se. Thu s far, m ethylene blu e ep id erm olysis, and fat necrosis are u su ally m anaged suc-
ap pears to be less allergenic (136), but caution m u st be cessfu lly w ithou t need for ad d itional su rgery. Wh en fat
exercised to avoid skin necrosis from d erm al injections of n ecrosis associated w ith a m ass is equ ivocal for local
this agent. recu rrence, then a need le or excisional biop sy m ay becom e
Blu e d yes can also cau se a sp u riou s d ecline in p u lse n ecessary.
oxim etry m easu rem ents, related to intravascular u p take
and interference w ith sp ectroscopy; arterial blood gas Nipple-Sparing Mastectomy
m easu rement in these circu mstances reveals norm al oxy- The nipple-sparing mastectomy (also know n as total skin-
genation. Ad d itionally, it shou ld be noted that blu e d yes sparing mastectomy) is occasionally performed to improve
cosmesis in a select subset of patients und ergoing a mastec- cep t, the long-term resu lts and rates of attend ant-infectious
tomy. Controversy exists regard ing the oncologic im plica- m orbid ity rem ain to be d efined .
tions of this proced ure, as it potentially can be associated
w ith excessive retained breast d uctal tissue in the nipple-are-
olar skin, or it can compromise the ad equacy of the mastec- ■ Other issues related to breast surgery
tomy related to resid ual breast tissue left in the elongated complication rates
skin flaps remote from the m astectomy incision. These risks
Neoadjuvant Chemotherapy
are problematic regardless of whether the mastectomy is
being performed therapeutically for a cancer diagnosis or The benefits of increased breast p reservation rates
for prophylaxis. A literature review by Chung and Sacchini (becau se of p rim ary tu m or d ow nstaging) and m onitoring
(140) reported complications specific to preservation of the of chem osensitivity have led to broad ened ap p lications
nipple-areolar complex. They found that nipple or areola for ind u ction chem otherap y regim ens. N u m erou s stu d ies
loss from ischemia or necrosis occurred in 2% to 20% of have d em onstrated the oncologic and m ed ical safety of
cases. N ipple-areolar necrosis can be associated w ith d evas- this ap p roach. H ow ever, p atients shou ld have their su r-
tating effects on the reconstructed breast; in one stud y, the gery tim ed w ith the last chem otherap y cycle so that ad e-
underlying implant/ tissue expander had to be sacrificed in qu ate bone m arrow recovery has occu rred (u su ally by 3 to
3 of 51 procedures or 5.8% (141). 4 w eeks), as evid enced by a p latelet cou nt 75,000 and an
absolu te neu trop hil cou nt 1,500.
Patients w ith u nifocal breast cancers and no m am m o-
IBR and Chest Wall Irradiation grap hically su sp iciou s calcifications w ho are receiving
Chest w all irrad iation can com prom ise reconstruction out- ind u ction chem otherap y in ord er to im p rove eligibility for
com e regard less of w hether the m astectom y and IBR are breast p reservation shou ld have rad io-op aqu e clip s
perform ed before or after the rad iation exposu re. Mastec- inserted into the tu m or bed by the first or second cycle of
tom y and IBR p erform ed on a p reviou sly irrad iated chest treatm ent. If no m arkers are inserted and the p atient has a
w all (as in the setting of p atients u nd ergoing su rgery for com p lete clinical resp onse, then she w ill be com m itted to
local recu rrence after prior BCT, or in breast cancer p atients a m astectom y becau se of inability to localize the tu m or
w ith a history of therap eu tic chest w all irrad iation for bed at tim e of lu m p ectom y. Alternatively, p atients w ith
H od gkin’s d isease) is m ore challenging becau se of the d iffu se su sp iciou s m icrocalcifications associated w ith
stiffer, less com p liant chest w all skin. Autogenou s tissu e their cancers and p atients w ith m u lticentric d isease
reconstru ctions are u su ally p referred in this setting becau se shou ld be inform ed at the tim e of d iagnosis that m astec-
of d ifficu lties in exp and ing the chest w all to accom m od ate tom y w ill be requ ired regard less of the m agnitu d e of
an im p lant. resp onse to ind u ction chem otherap y becau se of lim ited
Mastectom y and IBR are perform ed prior to irrad iation ability to accu rately m onitor significance of resp onse in
in cases requiring postm astectom y irrad iation (extensive these clinical scenarios (145).
nod al d isease, locally ad vanced breast cancer, or cases m as- The op tim al strategy for integrating lym p hatic m ap -
tectom y flap s w ith inad equate m argin control). In this set- p ing technology into neoad ju vant chem otherap y p roto-
ting, irrad iation of the reconstructed breast increases risk of cols also rem ains to be d efined . As show n in Table 44.4,
fat necrosis and w ound infection. Im plant reconstru ctions nu m erou s investigators have rep orted on the accu racy of
are p articu larly sensitive to this effect, and u p to one half sentinel lym p h nod e biop sies p erform ed after the d eliv-
w ill requ ire u ltim ate exp lantation becau se of contractu res ery of neoad ju vant chem otherap y, and the su ccess rates
and / or recu rrent infections (142). Som e investigators have have been qu ite varied . Id entification rates range from
rep orted that transverse rectu s abd om inu s m u scle (TRAM) 70% to 100% and false-negative rates range from 0% to
flap reconstructions tolerate irrad iation w ith acceptable 33%, w ith averages ap p roxim ating 90% and 9%, resp ec-
early resu lts (143), bu t m ore recent stud ies have ind icated tively. N onetheless, m any of these series reveal axillary
that on long-term follow -u p, there is increased m orbid ity, m etastases lim ited to the sentinel nod e, com p arable to the
includ ing high rates of fibrosis/ shrinkage and progressive p rim ary su rgery cases, and su p p orting the valid ity of the
d eform ity (144). Therefore, w hen there is a significant like- technology from a biologic p ersp ective. An alternative
lihood that p ostm astectom y irrad iation w ill be requ ired , strategy is to p erform the axillary staging via sentinel
patients shou ld be inform ed of the risks associated w ith lym p h nod e biop sy p rior to d elivery of the neoad ju vant
IBR and d elayed reconstru ction should be encou raged . An chem otherap y. Unfortu nately, this sequ ence com m its
alternative ap p roach that has been proposed is the inser- m any p atients to an “u nnecessary” com p letion axillary
tion of a tissu e exp and er at the tim e of m astectom y for the d issection, as the sentinel nod e(s) is the isolated site of
sole p u rp ose of skin exp ansion and w ith the p lan for final m etastases in a significant p rop ortion of p atients, and
surgery u p on com pletion of chest w all irrad iation, by chem otherap y can sterilize axillary m etastases in ap p rox-
either autogenous tissu e reconstru ction or exchange to the im ately one-qu arter of cases. This issu e rem ains to be fu r-
final im p lant. While this strategy m ay be reasonable in con- ther evalu ated in p rosp ective clinical trials.
Table 4 4 .4 Select ed st u d ies of lym p h a t ic m a p p in g a n d sen t in el lym p h n od e biop sy p er for m ed a ft er

n eoa d ju va n t ch em ot h era py
Sentinel Node Metastases Limited
Study T Status Sample Size Identification Rate False-Negative Rate to Sentinel Node(s)
Breslin et al., 2000 (160) 2,3 51 85% (42/51) 12% (3/25) 40% (10/25)
Nason et al., 2000 (161) 2,3 15 87% (13/15) 33% (3/9) 11% ( 1/9)
Haid et al., 2001 (162) 1–3 33 88% (29/33) 0% (0/22) 50% (11/22)
Fernandez et al., 2001 (163) 1–4 40 90% (36/40) 20% (4/20) 20% (4/20)
Tafra et al., 2001 (164) 1,2 29 93% (27/29) 0% (0/15) NR
Stearns et al., 2002 (165) 3,4 T4 d (inflammatory) 8 75% (6/8) 40% (2/5) 24% (5/21)
Noninflammatory 26 88% (23/26) 6% (1/16)
Julian et al., 2002 (166) 1–3 34 91% (31/34) 0% (0/12) 42% (5/12)
Miller et al., 2002 (167) 1–3 35 86% (30/35) 0% (0/9) 44% (4/9)
Brady, 2002 (168) 1–3 14 93% (13/14) 0% (0/10) 60% (6/10)
Piato et al., 2003 (169) 1,2 42 98% (41/42) 17% (3/18) 0% (0/18)
Balch et al., 2003 (170) 2–4 32 97% (31/32) 5% (1/19) 56% (10/18)
Schwartz and Meltzer, 2003 (171) 1–3 21 100% (21/21) 9% (1/11) 64% (7/11)
Reitsamer et al., 2003 (172) 2,3 30 87% (26/30) 7% (1/15) 53% (8/15)
Mamounas et al., 2005 (173, 174) 1–3 428 85% (363/428) 11% (15/140) 50% (70/140)
■ REFERENCES 16. Thom as R, Alvino P, Cortino GR, et al. Long-acting versu s short-act-
ing cep halosporins for preoperative prophylaxis in breast surgery: a
1. Gru nw ald Z, Moore JH , Schw artz GF. Bilateral brachial p lexu s p alsy rand om ized d ou ble-blind trial involving 1,766 p atients. Chemotherapy
after a right-sid e m od ified rad ical m astectom y w ith im m ed iate 1999;45:217–223.
TRAM flap reconstruction. Breast J 2003;9:41–43. 17. Gu pta R, Sinnett D, Carp enter R, et al. Antibiotic p rop hylaxis for p ost-
2. Gravante G, Araco A, Sorge R, et al. Postop erative w ou nd infections operative w ou nd infection in clean elective breast su rgery. Eur J Surg
after breast red u ctions: the role of sm oking and the am ou nt of tissu e Oncol 2000;26:363–366.
rem oved . Aesthetic Plastic Surgery 2008;32:25–31. 18. N ieto A, Lozan o M, Moro MT, et al. Determ in an ts of w ou nd in fec-
3. Felip pe WA, Werneck GL, Santoro-Lop es G. Su rgical site infection tions after su rgery for breast cancer. Zentralbl Gynakol 2002;124:
am ong w om en d ischarged w ith a d rain in situ after breast cancer su r- 429–433.
gery. World J Surg 2007;31:2293–2299. 19. Sorensen LT, H orby J, Friis E, et al. Sm oking as a risk factor for w ou nd
4. Catania S, Zu rrid a S, Veronesi P, et al. Mond or ’s d isease and breast healing and infection in breast cancer su rgery. Eur J Surg Oncol 2002;
cancer. Cancer 1992;69:2267–2270. 28:815–820.
5. H arris AT. Mond or ’s d isease of the breast can also occu r after a sonog- 20. Witt A, Yavu z D, Walchetsed er C, et al. Preop erative core need le
raphy-guid ed core biop sy. AJR Am J Roentgenol 2003;180:284–285. biopsy as an ind epend ent risk factor for w ou nd infection after breast
6. H ou MF, H u ang CJ, H u ang YS, et al. Mond or ’s d isease in the breast. su rgery. Obstet Gynecol 2003;101:745–750.
Kaohsiung J Med Sci 1999;15:632–639. 21. Tran CL, Langer S, Brod erick-Villa G, et al. Does reop eration p red is-
7. Jaberi M, Willey SC, Brem RF. Stereotactic vacu u m -assisted breast pose to postop erative w ou nd infection in w om en und ergoing opera-
biop sy: an u nu su al cau se of Mond or ’s d isease. AJR Am J Roentgenol tion for breast cancer? Am Surg 2003;69:852–856.
2002;179:185–186. 22. El-Tam er MB, Ward BM, Schifftner T, et al. Morbid ity and m ortality
8. Olsen MA, Lefta M, Dietz JR, et al. Risk factors for su rgical site infec- follow ing breast cancer surgery in w om en: national benchm arks for
tion after m ajor breast op eration. J Amer Coll Surg 2008;207:326–335. stand ard s of care. Ann Surg 2007;245:665–671.
9. H oefer R, Du Bois J, Ostrow L, et al. Wou nd com p lications follow ing 23. Platt R, Zu cker JR, Zaleznik DF, et al. Periop erative antibiotic p rop hy-
m od ified rad ical m astectom y: an analysis of p eriop erative factors. J laxis and w ou nd infection follow ing breast su rgery. J Antimicrob
Am Osteopath Assoc 1990;90:47–53. Chemother 1993;31(Su pp l B):43–48.
10. Wagm an LD, Tegtm eier B, Beatty JD, et al. A p rosp ective, rand om ized 24. H all JC, Willsher PC, H all JL. Rand om ized clinical trial of single-d ose
d ou ble-blind stu d y of the u se of antibiotics at the tim e of m astectom y. antibiotic p rophylaxis for non-reconstru ctive breast su rgery. Br J Surg
Surg Gynecol Obstet 1990;170:12–16. 2006;93:1342–1346.
11. Chen J, Gu tkin Z, Baw nik J. Postop erative infections in breast surgery. 25. Tejirian T, DiFronzo LA, H aigh PI. Antibiotic p rop hylaxis for p revent-
J Hosp Infect 1991;17:61–65. ing w ou nd infection after breast surgery: a system atic review and
12. Vinton AL, Traverso LW, Jolly PC. Wou nd com p lications after m od i- m etaanalysis. J Am Coll Surg 2006;203:729–734.
fied rad ical m astectom y com p ared w ith tylectom y w ith axillary 26. Penel N , Yazd anp anah Y, Chau vet MP, et al. Prevention of su rgical site
lym ph nod e d issection. Am J Surg 1991;161:584–588. infection after breast cancer surgery by targeted prophylaxis antibi-
13. Platt R, Zu cker JR, Zaleznik DF, et al. Prop hylaxis against w ou nd otic in p atients at high risk of su rgical site infection. J Surg Oncol 2007;
infection follow ing herniorrhap hy or breast su rgery. J Infect Dis 96: 124–129.
1992;166: 556–560. 27. Ind elicato DJ, Grobm yer SR, N ew lin H , et al. Delayed breast cellu litis:
14. Lip shy KA, N eifeld JP, Boyle RM, et al. Com p lications of m astectom y an evolving com p lication of breast conservation. Int J Radiat Oncol Biol
and their relationship to biop sy techniqu e. Ann Surg Oncol 1996;3: Phys 2006;66:1339–1346.
290–294. 28. Boostrom SY, Throckm orton AD, Bou ghey JC, et al. Incid ence of clini-
15. Bertin M, Crow e J, Gord on S. Determ inants of su rgical site infection cally significant serom a after breast and axillary su rgery. J Am Coll
after breast surgery. Am J Infect Control 1998;26:61–65. Surg 2009;208:148–150.
29. Pogson CJ, Ad w ani A, Ebbs SR. Serom a follow ing breast cancer su r- 56. Sed d ighzad eh A, Shetty R, Gold haber SZ. Venou s throm boem bolism
gery. Eur J Surg Oncol 2003;29:711–717. in p atients w ith active cancer. Thromb Haemost 2007;98:656–661.
30. Bonnem a J, Ligtensetein D, Wiggers T, et al. The com p osition of 57. Lee AY. Ep id em iology and m anagem ent of venou s throm boem bolism
serou s flu id after axillary d issection. Eur J Surg 1999;165:9–13. in p atients w ith cancer. Thromb Res 2003;110:167–172.
31. Giuliano AE, H aigh PI, Brennan MB, et al. Prosp ective observational 58. Winter PC. The p athogenesis of venou s throm boem bolism in cancer:
stu d y of sentinel lym phad enectom y w ithout fu rther axillary d issec- em erging links w ith tu m ou r biology. Hematol Oncol 2006;24:126–133.
tion in patients w ith sentinel nod e-negative breast cancer. J Clin Oncol 59. Decensi A, Maisonneuve P, Rotm ensz N , et al. Effect of tam oxifen on
2000;18:2553–2559. venou s throm boem bolic events in a breast cancer p revention trial.
32. Talbot ML, Magarey CJ. Red u ced u se of d rains follow ing axillary lym - Circulation 2005;111:650–656.
p had enectom y for breast cancer. ANZ J Surg 2002;72:488–490. 60. Kirw an CC, McDow ell G, McCollu m CN , et al. Early changes in the
33. Cam eron AE, Ebbs SR, Wylie F, et al. Su ction d rainage of the axilla: a haem ostatic and procoagulant system s after chem otherapy for breast
p rosp ective rand om ized trial. Br J Surg 1988;75:1211. cancer. Br J Cancer 2008;99:1000–1006.
34. Som ers R, Jablon L, Kap lan M. The u se of closed su ction d rainage 61. And tbacka RH , Babiera G, Singletary SE, et al. Incid ence and p reven-
after lu m pectom y and axillary d issection for breast cancer: a p rospec- tion of venou s throm boem bolism in patients und ergoing breast can-
tive rand om ized trial. Ann Surg 1992;215:146–149. cer su rgery and treated accord ing to clinical p athw ays. Ann Surg
35. Flew J. The effect of restriction of shou ld er m ovem ent. Br J Surg 2006;243: 96–101.
1979;66:302–305. 62. Friis E, H orby J, Sorensen LT, et al. Throm boem bolic p rop hylaxis as a
36. Lotz M, Du ncan M, Gerber L, et al. Early versu s d elayed shou ld er risk factor for postop erative com p lications after breast cancer su rgery.
m otion follow ing axillary d issection. Ann Surg 1981;193:288–295. World J Surg 2004;28:540–543.
37. Schultz I, Barrholm M, Grond al S. Delayed shou ld er exercises in 63. Patiar S, Kirw an CC, McDow ell G, et al. Prevention of venou s throm -
red u cing serom a frequ ency after m od ified rad ical m astectom y: a boem bolism in su rgical p atients w ith breast cancer. Br J Surg 2007;94:
prosp ective rand om ized stu d y. Ann Surg Oncol 1997;4:293–297. 412–420.
38. Porter KA, O’Connor S, Rim m E, et al. Electrocau tery as a factor in 64. Tasm u th T, von Sm itten K, Kalso E. Pain and other sym p tom s d u ring
serom a form ation follow ing m astectom y. Am J Surg 1998;176:8–11. the first year after rad ical and conservative su rgery for breast cancer.
39. Keogh G, Doughty J, McArd le C, et al. Serom a form ation related to Br J Cancer 1996;74:2024–2031.
electrocautery in breast su rgery—a p rosp ective, rand om ized trial. The 65. Tasm u th T, Blom qvist C, Kalso E. Chronic p ost-treatm ent sym p tom s
Breast 1998;7:39–41. in patients w ith breast cancer op erated in d ifferent su rgical u nits. Eur
40. Kontos M, Kothari A, H am ed H . Effect of harm onic scalpel on serom a J Surg Oncol 1999;25:38–43.
form ation follow ing su rgery for breast cancer: a p rosp ective rand om - 66. Stevens P, Dibble S, Miastowski C. Prevalence, characteristics, and
ized stu d y. J BUON 2008;13:223–230. impact of postmastectomy pain syndrome: an investigation of women’s
41. Classe J, Du pre P, Francois T, et al. Axillary p ad d ing as an alternative exp eriences. Pain 1995;61:61–68.
to closed suction d rain for am bu latory axillary lym p had enectom y. 67. Carpenter J, And rylkow ski M, Sloan P, et al. Postm astectom y/
Arch Surg 2002;137:169–173. postlumpectomy pain in breast cancer survivors. J Clin Epidemiol
42. O’H ea BJ, H o MN , Petrek JA. External com p ression d ressing versu s 1998;51: 1285–1292.
stand ard d ressing after axillary lymphad enectomy. Am J Surg 1999;177: 68. Tasm uth T, von Sm itten K, H ietanen P, et al. Pain and other sym p tom s
450–453. after d ifferent treatm ent m od alities of breast cancer. Ann Oncol 1995;6:
43. Kontos M, Petrou A, Prassas E, et al. Pressu re d ressing in breast su r- 453–459.
gery: is this the solu tion for serom a form ation? J BUON 2008;13:65–67. 69. Bishop SR, Warr D. Cop ing, catastrop hizing and chronic p ain in
44. Rice DC, Morris SM, Sarr MG, et al. Intraop erative top ical tetracycline breast cancer. J Behav Med 2003;26:265–281.
sclerotherap y follow ing m astectom y: a p rosp ective, rand om ized trial. 70. Fassou laki A, Melem eni A, Staikou C, et al. Acu te p ostop erative p ain
J Surg Oncol 2000;73:224–227. p red icts chronic p ain and long-term analgesic requ irem ents after
45. Burak WE Jr, Good m an P, You ng D. Serom a form ation follow ing axil- breast su rgery for cancer. Acta Anaesthesiol Belg 2008;59:241–248.
lary d issection for breast cancer: risk factors and lack of influ ence of 71. Poleshu ck EL, Katz J, And ru s CH , et al. Risk factors for chronic p ain
bovine throm bin. J Surg Oncol 1997;64:27–31. follow ing breast cancer su rgery: a p rosp ective stu d y. J Pain 2006;7:
46. Langer S, Guenther JM, DiFronzo LA. Does fibrin sealant red u ce 626–634.
d rain ou tp u t and allow earlier rem oval of d rainage catheters in 72. Tasm uth T, H artel B, Kalso E. Venlafaxine in neu rop athic p ain follow -
w om en und ergoing operation for breast cancer? Am Surg 2003;69: ing treatm ent of breast cancer. Eur J Pain 2002;6:17–24.
77–81. 73. Farrar WB, Fanning WJ. Elim inating the d og-ear in m od ified rad ical
47. Berger A, Tem p fer C, H artm ann B, et al. Sealing of p ostoperative axil- m astectom y. Am J Surg 1988;156:401–402.
lary leakage after axillary lym phad enectom y u sing a fibrin glue 74. Chretien-Marqu et B, Bennaceu r S. Dog ear: tru e and false. A sim p le
coated collagen p atch: a p rosp ective rand om ised stu d y. Breast Cancer su rgical m anagem ent. Dermatol Surg 1997;23:547–550; d iscu ssion 551.
Res Treat 2001;67:9–14. 75. Mirza M, Sinha KS, Fortes-Mayer K. Tear-d rop incision for m astec-
48. Moore M, Bu rak WE Jr, N elson E, et al. Fibrin sealant red u ces the tom y to avoid d og-ear d eform ity. Ann R Coll Surg Engl 2003;85:131.
d u ration and am ou nt of flu id d rainage after axillary d issection: a ran- 76. Meric F, Buchholz TA, Mirza N Q, et al. Long-term com p lications asso-
d om ized p rospective clinical trial. J Am Coll Surg 2001;192:591–599. ciated w ith breast-conservation su rgery and rad iotherap y. Ann Surg
49. Paterson ML, N athanson SD, H avstad S. H em atom as follow ing exci- Oncol 2002;9:543–549.
sional breast biopsies for invasive breast carcinom a: the influence of 77. Fehlau er F, Tribius S, H oller U, et al. Long-term rad iation sequ elae
d eep su ture app roxim ation of breast p arenchym a. Am Surg 1994;60: after breast-conserving therapy in w om en w ith early-stage breast can-
845–848. cer: an observational stu d y u sing the LEN T-SOMA scoring system . Int
50. Sharm a S, Chang DW, Kou tz C, et al. Incid ence of hem atom a associ- J Radiat Oncol Biol Phys 2003;55:651–658.
ated w ith ketorolac after TRAM flap breast reconstruction. Plast 78. Collette S, Collette L, Bu d iharto T, et al. Pred ictors of the risk of fibro-
Reconstr Surg 2001;107:352–355. sis at 10 years after breast conserving therap y for early breast cancer: a
51. H od ges P, Kam P. The p eriop erative im p lications of herbal m ed icines. stud y based on the EORTC Trial 22881–10882 ‘boost versu s no boost’.
Anaesthesia 2002;57:889–899. Eur J Cancer 2008;44:2587–2599.
52. Ang-Lee M, Moss J, Yu an C. H erbal m ed icines and p eriop erative care. 79. LEN T-SOMA scales for all anatom ic sites. Int J Radiat Oncol Biol Phys
JAMA 2001;286:208–216. 1995;31:1049–1091.
53. H ard y RG, William s L, Dixon JM. Use of enoxap arin results in m ore 80. Tsai RJ, Dennis LK, Lynch CF, et al. The risk of d evelop ing arm lym -
haem orrhagic com plications after breast su rgery than unfractionated p hed em a am ong breast cancer survivors: a m eta-analysis of treatm ent
heparin. Br J Surg 2008;95:834–836. factors. Ann Surg Oncol 2009;16:1959–1972.
54. Somerville P, Seifert PJ, Destounis SV, et al. Anticoagulation and bleeding 81. Moyer H R, Carlson GW, Styblo TM, et al. Three-d im ensional d igital
risk after core needle biopsy. AJR Am J Roentgenol 2008;191:1194–1197. evaluation of breast sym m etry after breast conservation therap y. J Am
55. Levitan N , Dow lati A, Rem ick SC, et al. Rates of initial and recu rrent Coll Surg 2008;207:227–232.
throm boem bolic d isease am ong patients w ith m alignancy versu s 82. Zip pel D, Siegelm ann-Danieli N , Ayalon S, et al. Delayed breast cel-
those w ithou t m alignancy. Risk analysis u sing Med icare claim s d ata. lu litis follow ing breast conserving op eration. Eur J Surg Oncol 2003;29:
Medicine (Baltimore) 1999;78:285–291. 327–330.
83. Brew er VH , H ahn KA, Rohrbach BW, et al. Risk factor analysis for 111. Giu liano AE, Kirgan DM, Gu enther JM, et al. Lym p hatic m ap p ing and
breast cellu litis com p licating breast conservation therap y. Clin Infect sentinel lym phad enectom y for breast cancer. Ann Surg 1994;220:
Dis 2000;31:654–659. 391–398; d iscu ssion 398–401.
84. Staren ED, Klep ac S, Sm ith AP, et al. The d ilem m a of d elayed cellulitis 112. Kim T, Agboola O, Lym an G. Lym p hatic m ap p ing and sentinel lym p h
after breast conservation therap y. Arch Surg 1996;131:651–654. nod e sam pling in breast cancer. In: Proceedings of the American Society
85. Rescigno J, McCorm ick B, Brow n AE, et al. Breast cellu litis after con- of Clinical Oncology 2002 Annual Symposium, Orlando, FL. Chicago:
servative su rgery and rad iotherap y. Int J Radiat Oncol Biol Phys Am erican Society of Clinical Oncology; 2002.
1994;29: 163–168. 113. Cox CE, Bass SS, Bou lw are D, et al. Im p lem entation of new su rgical
86. Miller SR, Mon d ry T, Reed JS, et al. Delayed cellu litis associated technology: ou tcom e m easu res for lym phatic m app ing of breast carci-
w ith conservative therap y for breast cancer. J Surg Oncol 1998;67: nom a. Ann Surg Oncol 1999;6:553–561.
242–245. 114. Derossis AM, Fey J, Yeu ng H , et al. A trend analysis of the relative
87. Gu tt R, Correa CR, H w ang WT, et al. Card iac m orbid ity and m ortality value of blu e d ye and isotop e localization in 2,000 consecu tive cases
after breast conservation treatm ent in p atients w ith early-stage breast of sentinel nod e biop sy for breast cancer. J Am Coll Surg 2001;193:
cancer and preexisting card iac d isease. Clin Breast Cancer 2008;8: 473–478.
443–448. 115. H aigh PI, H ansen N M, Qi K, et al. Biop sy m ethod and excision vol-
88. Keisch M, Vicini F, Ku ske RR, et al. Initial clinical exp erience w ith the u m e d o not affect su ccess rate of su bsequ ent sentinel lym p h nod e d is-
Mam m oSite breast brachytherap y ap p licator in w om en w ith early- section in breast cancer. Ann Surg Oncol 2000;7:21–27.
stage breast cancer treated w ith breast-conserving therap y. Int J Radiat 116. Wong SL, Ed w ard s MJ, Chao C, et al. The effect of p rior breast biop sy
Oncol Biol Phys 2003;55:289–293. m ethod and concu rrent d efinitive breast proced u re on success and
89. Monroe AT, Feigenberg SJ, Mend enhall N P. Angiosarcom a after accu racy of sentinel lym p h nod e biop sy. Ann Surg Oncol 2002;9:
breast-conserving therap y. Cancer 2003;97:1832–1840. 272–277.
90. Ed eiken S, Ru sso DP, Knecht J, et al. Angiosarcom a after tylectom y 117. Linehan DC, H ill AD, Akhu rst T, et al. Intrad erm al rad iocolloid and
and rad iation therap y for carcinom a of the breast. Cancer 1992;70: intraparenchym al blue d ye injection optim ize sentinel nod e id entifi-
644–647. cation in breast cancer patients. Ann Surg Oncol 1999;6:450–454.
91. Feigenberg SJ, Mend enhall N P, Reith JD, et al. Angiosarcom a after 118. Chao C, Wong SL, Woo C, et al. Reliable lym p hatic d rainage to axil-
breast-conserving therap y: exp erience w ith hyp erfractionated rad io- lary sentinel lym ph nod es regard less of tum or location w ithin the
therapy. Int J Radiat Oncol Biol Phys 2002;52:620–626. breast. Am J Surg 2001;182:307–311.
92. H od gson N C, Bow en-Wells C, Moffat F, et al. Angiosarcom as of the 119. Veronesi U, Paganelli G, Galim berti V, et al. Sentinel-nod e biop sy to
breast: a review of 70 cases. Am J Clin Oncol 2007;30:570–573. avoid axillary d issection in breast cancer w ith clinically negative
93. Fisher B, Brow n A, Mam ou nas E, et al. Effect of p reoperative lym p h-nod es. Lancet 1997;349:1864–1867.
chem otherapy on local-regional d isease in w om en w ith operable 120. Veronesi U, Paganelli G, Viale G, et al. Sentinel lym p h nod e biop sy
breast cancer: find ings from N ational Su rgical Ad ju vant Breast and and axillary d issection in breast cancer: resu lts in a large series. J Natl
Bow el Project B-18. J Clin Oncol 1997;15:2483–2493. Cancer Inst 1999;91:368–373.
94. Liberm an L, Good stone S, Dershaw D. One op eration after percu ta- 121. Bed rosian I, Reynold s C, Mick R, et al. Accu racy of sentinel lym p h
neous d iagnosis of nonpalpable breast cancer: frequ ency and associ- nod e biop sy in p atients w ith large p rim ary tu m ors. Cancer 2000;88:
ated factors. AJR Am J Roentgenol 2002;178:673–679. 2540–2545.
95. Singletary SE, Dow latshahi K, Dooley W et al. Minim ally invasive 122. Chu ng MH , Ye W, Giu liano AE. Role for sentinel lym p h nod e d issec-
operation for breast cancer. Curr Prob Surg 2004;41:394–447. tion in the m anagem ent of large ( or 5 cm ) invasive breast cancer.
96. Montrey JS, Levy JA, Brenner RJ. Wire fragm ents after need le localiza- Ann Surg Oncol 2001;8:688–692.
tion. AJR Am J Roentgenol 1996;167:1267–1269. 123. Klim berg VS, Ru bio IT, H enry R, et al. Su bareolar versu s p eritu m oral
97. Petrasek AJ, Sem p le JL, McCread y DR. The su rgical and oncologic injection for location of the sentinel lym p h nod e. Ann Surg 1999;
significance of the axillary arch d u ring axillary lym phad enectom y. 229:860–864; d iscu ssion 864–865.
Can J Surg 1997;40:44–47. 124. Bau er TW, Spitz FR, Callans LS, et al. Su bareolar and p eritu m oral
98. Wright FC, Walker J, Law CH , et al. Ou tcom es after localized axillary injection id entify sim ilar sentinel nod es for breast cancer. Ann Surg
nod e recu rrence in breast cancer. Ann Surg Oncol 2003;10:1054–1058. Oncol 2002;9:169–176.
99. Erickson VS, Pearson ML, Ganz PA, et al. Arm ed em a in breast cancer 125. Kern KA. Breast lym p hatic m ap p ing u sing su bareolar injections of
p atients. J Natl Cancer Inst 2001;93:96–111. blue d ye and rad iocolloid : illu strated techniqu e. J Am Coll Surg 2001;
100. Beau lac SM, McN air LA, Scott TE, et al. Lym p hed em a and qu ality of 192:545–550.
life in survivors of early-stage breast cancer. Arch Surg 2002;137: 126. Jin Kim H , H eerd t AS, Cod y H S, et al. Sentinel lym p h nod e d rainage
1253–1257. in m u lticentric breast cancers. Breast J 2002;8:356–361.
101. Sener SF, Winchester DJ, Martz CH , et al. Lym p hed em a after sentinel 127. Kum ar R, Jana S, H eiba S, et al. Retrosp ective analysis of sentinel nod e
lym p had enectom y for breast carcinom a. Cancer 2001;92:748–752. localization in m u ltifocal, m u lticentric, p alp able, or nonp alp able
102. Roses DF, Brooks AD, H arris MN , et al. Com p lications of level I and II breast cancer. J Nucl Med 2003;2003:7–10.
axillary d issection in the treatm ent of carcinom a of the breast. Ann 128. Tou sim is E, van Zee K, Fey J, et al. The accu racy of sentinel lym p h
Surg 1999;230:194–201. nod e biop sy in m u lticentric and m u ltifocal invasive breast cancers.
103. Thom p son M, Korourian S, H enry-Tillm an R, et al. Axillary reverse J Am Coll Surg 2003;197:529–535.
m app ing (ARM): a new concep t to id entify and enhance lym p hatic 129. Zavagno G, Meggiolaro F, Rossi C, et al. Su bareolar injection for sen-
p reservation. Ann Surg Oncol 2007;14:1890–1895. tinel lym p h nod e location in breast cancer. Eur J Surg Oncol 2002;28:
104. Grobm yer SR, Daly JM, Glotzbach RE, et al. Role of su rgery in the 701–704.
m anagem ent of postm astectom y extrem ity angiosarcom a (Stew art– 130. Schrenk P, Wayand W. Sentinel nod e biop sy in axillary lym p h nod e
Treves synd rom e). J Surg Oncol 2000;73:182–188. staging for p atients w ith m u lticentric breast cancer. Lancet 2001;
105. Janse AJ, van Coevord en F, Peterse H , et al. Lym p hed em a-ind u ced 357:122.
lym p hangiosarcom a. Eur J Surg Oncol 1995;21:155–158. 131. Leid eniu s M, Lep panen E, Krogeru s L, et al. Motion restriction and
106. Stew art FW, Treves N . Classics in oncology: lym p hangiosarcom a in axillary w eb synd rom e after sentinel nod e biopsy and axillary clear-
p ostm astectom y lym p hed em a: a rep ort of six cases in elep hantiasis ance in breast cancer. Am J Surg 2003;185:127–130.
chiru rgica. CA Cancer J Clin 1981;31:284–299. 132. Lau rie SA, Khan DA, Gru challa RS, et al. Anap hylaxis to isosu lfan
107. Moskovitz AH , And erson BO, Yeu ng RS, et al. Axillary w eb synd rom e blue. Ann Allergy Asthma Immunol 2002;88:64–66.
after axillary d issection. Am J Surg 2001;181:434–439. 133. Efron P, Knu d sen E, H irshorn S, et al. Anap hylactic reaction to isosu l-
108. Calu w e GL, Christiaens MR. Chylou s leak: a rare com p lication after fan blu e used for sentinel nod e biopsy: case report and literature
axillary lym ph nod e d issection. Acta Chir Belg 2003;103:217–218. review. Breast J 2002;8:396–399.
109. Carcoforo P, Soliani G, Maestroni U, et al. Octreotid e in the treatm ent 134. Sad iq TS, Bu rns WW III, Taber DJ, et al. Blu e u rticaria: a p reviou sly
of lym p horrhea after axillary nod e d issection: a prosp ective rand om - u nrep orted ad verse event associated w ith isosu lfan blu e. Arch Surg
ized controlled trial. J Am Coll Surg 2003;196:365–369. 2001;136:1433–1435.
110. Krag DN , Weaver DL, Alex JC, et al. Su rgical resection and rad iolocal- 135. Cim m ino VM, Brow n AC, Szocik JF, et al. Allergic reactions to isosu l-
ization of the sentinel lym ph nod e in breast cancer u sing a gam m a fan blue d u ring sentinel nod e biop sy—a com m on event. Surgery
p robe. Surg Oncol 1993;2:335–339; d iscu ssion 340. 2001;130:439–442.
136. Mostafa A, Carpenter R. Re: Anaphylaxis to patent blue d ye during sen- 156. Montgom ery LL, Thorne AC, Van Zee KJ, et al. Isosu lfan blu e d ye
tinel lymph nod e biopsy for breast cancer. Eur J Surg Oncol 2001;27:610. reactions d u ring sentinel lym ph nod e m apping for breast cancer.
137. N ew m an LA, Ku erer H M, H u nt KK, et al. Presentation, treatm ent, Anesth Analg 2002;95:385–388, table of contents.
and outcom e of local recu rrence afterskin-sp aring m astectom y and 157. Stefanutto TB, Shapiro WA, Wright PM. Anap hylactic reaction to iso-
im m ed iate breast reconstru ction. Ann Surg Oncol 1998;5:620–626. sulfan blu e. Br J Anaesth 2002;89:527–528.
138. Med ina-Franco H , Vasconez LO, Fix RJ, et al. Factors associated w ith 158. Crivellaro M, Senna G, Dam a A, et al. Anap hylaxis d u e to p atent blu e
local recu rrence after skin-sp aring m astectom y and im m ed iate breast d ye d u ring lym p hograp hy, w ith negative skin p rick test. J Investig
reconstru ction for invasive breast cancer. Ann Surg 2002;235:814–819. Allergol Clin Immunol 2003;13:71–72.
139. Rivad eneira DE, Sim m ons RM, Fish SK, et al. Skin-sp aring m astec- 159. Sp ru ng J, Tully MJ, Ziser A. Anap hylactic reactions to isosu lfan blu e
tom y w ith im m ed iate breast reconstru ction: a critical analysis of local d ye d uring sentinel nod e lym p had enectom y for breast cancer. Anesth
recurrence. Cancer J 2000;6:331–335. Analg 2003;96:1051–1053, table of contents.
140. Chu ng AP, Sacchini V. N ip p le-sp aring m astectom y: w here are w e 160. Breslin TM, Cohen L, Sahin A, et al. Sentinel lym p h nod e biop sy is
now ? Surg Oncol 2008;17:261–266. accurate after neoad ju vant chem otherap y for breast cancer. J Clin
141. Caruso F, Ferrara M, Castiglione G, et al. N ipp le sp aring subcutaneou s Oncol 2000;18:3480–3486.
m astectom y: sixty-six m onths follow -u p . Eur J Surg Oncol 2006;32: 161. N ason KS, And erson BO, Byrd DR, et al. Increased false negative sen-
937–940. tinel nod e biop sy rates after p reoperative chem otherapy for invasive
142. N ew m an LA, Ku erer H M, H u nt KK, et al. Feasibility of im m ed iate breast carcinom a. Cancer 2000;89:2187–2194.
breast reconstru ction for locally ad vanced breast cancer. Ann Surg 162. H aid A, Tau sch C, Lang A, et al. Is sentinel lym p h nod e biop sy reliable
Oncol 1999;6:671–675. and ind icated after preop erative chem otherap y in patients w ith
143. H u nt KK, Bald w in BJ, Strom EA, et al. Feasibility of p ostm astectom y breast carcinom a? Cancer 2001;92:1080–1084.
rad iation therapy after TRAM flap breast reconstru ction. Ann Surg 163. Fernand ez A, Cortes M, Benito E, et al. Gam m a p robe sentinel nod e
Oncol 1997;4:377–384. localization and biopsy in breast cancer patients treated w ith a neoad -
144. Tran N V, Evans GR, Kroll SS, et al. Postop erative ad ju vant irrad iation: ju vant chem otherapy schem e. Nucl Med Commun 2001;22:361–366.
effects on transverse rectu s abd om inis m uscle flap breast reconstru c- 164. Tafra L, Verbanac KM, Lannin DR. Preoperative chemotherapy and sen-
tion. Plast Reconstr Surg 2000;106:313–317; d iscu ssion 318–320. tinel lymphadenectomy for breast cancer. Am J Surg 2001;182:312–315.
145. N ew m an LA, Buzd ar AU, Singletary SE, et al. A p rosp ective trial of 165. Stearns V, Ew ing CA, Slack R, et al. Sentinel lym p had enectom y after
p reop erative chem otherap y in resectable breast cancer: pred ictors neoad juvant chem otherapy for breast cancer m ay reliably represent
of breast-conservation therap y feasibility. Ann Surg Oncol 2002;9: the axilla except for inflam m atory breast cancer. Ann Surg Oncol
228–234. 2002;9:235–242.
146. Canavese G, Gip p oni M, Cattu rich A et al. Technical issu es and p atho- 166. Ju lian TB, Du si D, Wolm ark N . Sentinel nod e biop sy after neoad ju -
logic im plications of sentinel lym p h nod e biopsy in early-stage breast vant chem otherapy for breast cancer. Am J Surg 2002;184:315–317.
cancer patients. J Surg Oncol 2001; 77:81–87. 167. Miller AR, Thom ason VE, Yeh IT, et al. Analysis of sentinel lym p h
147. Albertini JJ, Lyman GH, Cox C, et al. Lymphatic mapping and sentinel nod e m apping w ith im m ed iate pathologic review in patients receiv-
nod e biopsy in the patient w ith breast cancer. JAMA 1996;276: ing p reop erative chem otherap y for breast carcinom a. Ann Surg Oncol
1818–1822. 2002;9:243–247.
148. McMasters KM, Tu ttle TM, Carlson DJ, et al. Sentinel lym ph nod e 168. Brad y EW. Sentinel lym p h nod e m ap p ing follow ing neoad ju vant
biop sy for breast cancer: a su itable alternative to rou tine axillary d ischem otherap y for breast cancer. Breast J 2002;8:97–100.
section in m ulti-institu tional practice w hen optim al technique is used . 169. Piato JR, Barros AC, Pincerato KM, et al. Sentinel lym p h nod e biop sy
J Clin Oncol 2000;18:2560–2566. in breast cancer after neoad ju vant chem otherap y. A p ilot stu d y. Eur J
149. Cox CE, Pend as S, Cox JM, et al. Gu id elines for sentinel nod e biopsy Surg Oncol 2003;29:118–120.
and lym phatic m ap p ing of p atients w ith breast cancer. Ann Surg 170. Balch GC, Mithani SK, Richard s KR, et al. Lym p hatic m ap p ing and
1998;227:645–651; d iscu ssion 651–653. sentinel lym p had enectom y after p reop erative therap y for stage II and
150. Krag D, Weaver D, Ashikaga T, et al. The sentinel nod e in breast can- III breast cancer. Ann Surg Oncol 2003;10:616–621.
cer—a m ulticenter valid ation stu d y. N Engl J Med 1998;339:941–946. 171. Schw artz GF, Meltzer AJ. Accu racy of axillary sentinel lym p h nod e
151. O’H ea BJ, H ill AD, El-Shirbiny AM, et al. Sentinel lym p h nod e biopsy biop sy follow ing neoad ju vant (ind u ction) chem otherap y for carci-
in breast cancer: initial experience at Mem orial Sloan-Kettering Can- nom a of the breast. Breast J 2003;9:374–379.
cer Center. J Am Coll Surg 1998;186:423–427. 172. Reitsam er R, Peintinger F, Rettenbacher L, et al. Sentinel lym p h nod e
152. Gu enther JM. Axillary d issection after u nsu ccessfu l sentinel lym - biopsy in breast cancer p atients after neoad ju vant chem otherap y. J
p had enectom y for breast cancer. Am Surg 1999;65:991–994. Surg Oncol 2003;84:63–67.
153. Lyew MA, Gam blin TC, Ayou b M. System ic anap hylaxis associated 173. Mam ounas EP, Brow n A, And erson S, et al. Sentinel nod e biop sy after
w ith intram am m ary isosu lfan blue injection used for sentinel nod e neoad juvant chem otherapy in breast cancer: results from N ational
d etection u nd er general anesthesia. Anesthesiology 2000;93:1145–1146. Surgical Ad ju vant Breast and Bow el Project Protocol B-27. J Clin Oncol
154. Mullan MH , Deacock SJ, Qu iney N F, et al. Anap hylaxis to p atent blu e 2005;23:2694–2702.
d ye d u ring sentinel lym p h nod e biop sy for breast cancer. Eur J Surg 174. Mam ounas E, Brow n A, Sm ith R, et al. Accuracy of sentinel lym ph
Oncol 2001;27:218–219. nod e biopsy after neoad ju vant chem otherap y in breast cancer:
155. Albo D, Wayne JD, H u nt KK, et al. Anap hylactic reactions to isosu lfan up d ated resu lts from N SABP B-27 (abstract #140), Presented at the
blu e d ye d u ring sentinel lym p h nod e biop sy for breast cancer. Am J Am erican Society of Clinical Oncology 38th Annu al Meeting, Orland o,
Surg 2001;182:393–398. FL, 2002.
CHAPTER
45
Complications of Soft-Tissue
Tumor Surgery
Sandra L. Wong
■ INTRODUCTION com p lications from the d efinitive op eration. If the p rim ary
lesion is su fficiently broad based and variegated in appear-
Surgical proced ures d one for soft-tissue tumors include ance, p u nch biop sy is a p referred m ethod of sam pling.
biopsies for d iagnosis, resections of the primary site w ith en Selection of the site of biop sy shou ld be based on the loca-
bloc structures as necessary, and sentinel nod e biopsies/ tion m ost likely to rep resent the thickest p ortion of the
completion lymph node dissections. The surgical manage- lesion so that an accurate Breslow d epth can be rend ered
ment of cutaneous melanoma, soft-tissue sarcoma, and sev- on histop athologic exam ination. Since interm ed iate-thick-
eral other types of soft-tissue neoplasm s can be associated ness (1 to 4 m m Breslow d ep th) and thick ( 4 m m )
w ith many potential, although rarely life-threatening, com- melanom as can be consid ered for regional staging w ith
plications. Meticulous attention to d etail throughout all sentinel lym p h nod e biop sy (SLN B), it is im p ortant to
aspects of soft-tissue surgery w ill minimize ad verse out- obtain rep resentative sam p ling.
comes. A thorough d iscussion w ith patients should includ e If an incisional biop sy is p erform ed instead , it is im por-
the possible risks of any operation, such as postoperative tant to ensu re that incisions are oriented su ch that a d efini-
bleed ing, infection, hematoma and / or seroma formation, tive resection can be p erform ed w ith m inim al m orbid ity.
d amage to surround ing structures, inability to completely Sp ecifically, in cases of extrem ity lesions, incisions m u st be
resect, recurrence d espite resection, and other com plications mad e along the vertical axis rather than transversely. The
associated w ith anesthesia and hospitalization (e.g., throm- ap p roach for d efinitive resection is d ep end ent on the initial
boembolism, myocard ial infarction, and pneumonia). Spe- incision and su rgical proced u res carry ad d itional m orbid -
cific risks w ith soft-tissue tumors are usually related to the ity if im prop erly oriented incisions preclud e p rim ary
tumor ’s location and extent of resection. closu re, lead ing to u se of skin grafting. (Fig. 45.1).
■ MELANOMA ■ Excision of the primary and complex closures

Surgical management of a cutaneous melanoma usually The surgical treatment of melanoma begins w ith the proper
begins w ith the id entification of the primary lesion, w hich management of the primary lesion. An excess of 90% of all
presents as a suspicious nevus. The spectrum of necessary thin primary melanomas ( 1 mm Breslow d epth) can be
treatment and prognosis associated w ith a diagnosis of cured w ith surgical excision alone, using 1-cm margins cir-
melanoma is largely dependent on stage at presentation, and cumferentially and soft-tissue resection d own to the fascial
this can be grouped as localized, regional, or metastatic dis- layer. Generally, 2-cm margins are used for thicker lesions
ease. Surgical resection and surgical staging are important ( 1 to 2 mm). Straightforw ard elliptical excisions follow ed
components of treatment for localized melanoma. Nod al by primary closure are commonly used. The length of the
metastases, either microscopic or bulky, should be resected long axis of the ellipse can be measured in a 3:1 or 4:1 man-
w hen possible for regional disease control. Because of the ner to ensure ad equate full-thickness closure w ithout und ue
lack of effective ad juvant therapies for melanoma, there is a tension or cosmetically unappealing “d og-ears” at the
lack of consensus about stand ard surgical therapies for periphery. Alternatively, dog-ears can be trimmed follow ing
ad vanced or metastatic melanoma, although resection could resection of the primary w ith ad equate margins. Sensitive
be consid ered for selected patients. sites such as the face or d igits require special attention and
mod ified surgical techniques for resection and closure.
■ Biopsy of the primary lesion Large transverse incisions along the extremities and
trunk w ith extensive und ermining of the surround ing skin
Principles of a good biopsy mu st be ad hered to in ord er to flaps are at high risk of seroma and / or hematoma formation
p rovid e an accu rate d iagnosis and to prevent d ow nstream in the postoperative period . Cutaneous nerves are necessar-
ily transected d uring soft-tissue tumor excision, often result-
Sandra L. Wong: Division of Su rgical Oncology, Dep art- ing in transient sensory deficits and numbness surrounding
m ent of Su rgery, University of Michigan, Ann Arbor, MI. th e incision . Th is is esp ecially tru e for excision s of
594
Chapter 45 • Complications of Soft-Tissue Tumor Surgery 595
excessive shear forces and infection should be m inim ized

in the early p ostop erative p eriod . In the era of SLN B, m any
su rgeons have increasingly u sed fu ll-thickness skin grafts
harvested from the nod e biopsy site to close d efects that
w ou ld otherw ise requ ire sp lit-thickness skin grafting from
a third su rgical site (1). H ow ever, d ecisions about thickness
of skin grafts shou ld take recip ient sites into consid eration,
A
since contractile p rop erties of the graft are d irectly related
to the qu antity of elastic fibers in the graft u sed . Sp lit-
thickness grafts have few er elastic fibers and u ltim ately
have m ore contraction over tim e. Fu ll-thickness grafts are
u su ally better able to resist w ou nd contraction and can
resu lt in better aesthetic and fu nctional ou tcom es for
anatom ic sites su ch as the face and hand s.
Tissue rearrangement can provid e excellent soft-tissue
coverage through the use of local, regional, or distant (pedi-
cled or free tissue transfer) flaps. Flaps are tissue that are
transplanted with vascular supply. Complex rearrangements
can be time consuming and often necessitate expertise w ith
microvascular surgery. Flap loss is often associated w ith
arterial insufficiency or poor venous outflow and can be a
d evastating complication, requiring long-term w ound man-
agement. Optimal healing occurs when blood supply is
ample and tissue quality is not compromised by factors that
B presage poor w ound healing, such as poor nutritional status,
use of corticosteroids, diabetes, or prior rad iation to the site.
FIGURE 45.1. Transversely oriented incisions for extremity melanomas
should be avoided. An incisional biopsy done with a transversely oriented Occasion ally, skin grafts or other com p lex recon stru c-
incision (arrows) resulted in two complications: (A) residual disease/local tion op tion s sh ou ld be p lan n ed as staged p roced u res if
recurrences at the extremes of the incision, and (B) a subsequent wide exci- th ere is an y con cern abou t in volvem en t of su rgical m ar-
sion with 2 cm margins resulted in a defect requiring skin graft closure as
gin s. A tem p orary coverin g can be u sed over th e site,
opposed to primary closure.
giving p athologists several d ays to d eterm ine a final
histop athologic d iagnosis w ith m argin statu s. It is im por-
melanomas on the face, head , and neck, w ith the possibility tant to u nd erstand that rem oval of the ap p rop riate su rgical
of inad vertent d amage to many important structures, such m argins w ith the excision of a p rim ary m elanom a is instru -
as the facial, spinal accessory, vagus, and hypoglossal nerves, m ental in m inim izing the risk of local tu m or recu rrence
and vascular structures, such as the external and internal p rior to d efinitive closu re.
jugular vein and internal carotid artery. Tumor location may
dictate other areas sensitive to tumor involvement (requir-
ing intentional sacrifice) or inadvertent injury, such as adja-
■ Diagnosis and management of regional disease
cent nerves, arteries, veins, and vital structures. Wound H istorically, the elective lym p h nod e d issection w as the
infections can occur as soon as 12 to 24 hours after an opera- m ain op eration p erform ed for the staging of p atients p re-
tion, and special attention should be given to rare, but poten- senting w ith localized m elanom a. This involved the
tially morbid and even lethal necrotizing infections, such as removal of clinically nonp alp able lym p h nod es, in contrast
necrotizing fasciitis or clostridial infections. to palpable ad enopathy that w ou ld be rem oved by a thera-
In general, attem pts shou ld be m ad e to ad equ ately p eu tic lym p h nod e d issection. For p atients w ithout clini-
excise the prim ary lesion w hile m inim izing scar form ation cally ap p arent d isease, the evalu ation and management of
and the need for skin grafts. For locations su ch as the d istal the d raining lym ph nod e basins in patients w ith interm ed i-
extrem ities, joints, head and neck, hand s, and feet, p rim ary ate-thickness (or thick) m elanom as has evolved from d is-
closu re is often not possible and other reconstructive cu ssions regard ing elective lym p h nod e d issection to m ore
options m u st be consid ered . Soft-tissu e coverage w ith ad ja- rou tine u se of SLN B. SLN B is a m inim ally invasive proce-
cent tissu e rearrangem ent or skin graft is often the pre- d u re, w hich typ ically u ses a com bination of rad ioactive
ferred m ethod of closure. tracer agents and isosulfan blue d ye to reliably id entify the
Skin grafts are associated w ith a higher su rgical m or- first d raining nod es, lead ing to accu rate p athological nod al
bid ity, cosm etic d isfigu rem ent, and overall cost comp ared staging of the entire nod al basin. Cu rrently accepted rec-
w ith p rim ary closu re. Possibility of skin graft failu re or om m end ations follow ing find ings of nod al m etastases
poor healing of the graft shou ld be fu lly explained to the inclu d e com p letion lym p had enectom y (2), and so SLN B
patient p rior to surgery and know n risk factors su ch as incisions shou ld be p lanned accord ingly in ord er to allow
en bloc resection of the biopsy incision w ith the m ain spec- p ing agent. A recent nationw id e shortage of isosu lfan blue
im en at tim e of the d efinitive proced u re. d ye as w ell as concerns abou t its relatively high cost, have
While the SLN B p roced u re itself u tilizes a m uch sm aller d riven the u se of m ethylene blu e d ye as an alternative
incision and a sm all field of d issection than a fu ll lym ph agent for SLN B. The sid e effect p rofile of m ethylene blu e
nod e d issection, there are several w ell-d escribed com p lica- d iffers from that of m ethylene blu e and w arrants sep arate
tions sp ecific to the SLN B proced u re. Comp lications sp ecif- consid eration. Anap hylactic reactions are not rep orted , but
ically associated w ith SLN B (3) have been reported . In cross-reactivity betw een blu e d yes is p ossible (7). There
patients w ho u nd erw ent an SLN B alone, com m on com p li- have been rep orts of cu taneou s reactions su ch as skin ery-
cations inclu d ed w ou nd infection, hematom a/ serom a for- them a, u lcers, and necrosis associated w ith the site of intra-
mation, and sensory nerve injury. Other less common d erm al injection in u p to 21% of p atients (10,11). More
complications that w ere noted includ ed hemorrhage, motor subtle inflam m atory cutaneou s ad verse effects su ch as cel-
nerve inju ry, d eep venous throm bosis, lym phed em a, and lu litis or fat necrosis m ay be noted even w hen frank skin
even throm bophlebitis. Com plication rates vary from stu d y necrosis is not p resent (12). Deep er (su bcu taneou s) injec-
to stu d y, ranging from 0.7% to 9% in reports of consecu tive tions or u se of either a low er total volu m e or d ilu ted m eth-
sentinel nod e biop sies for melanom a, all of w hich w ere ylene blu e solu tion have been rep orted to am eliorate su ch
consid ered m inor in natu re (3–5). reactions and are recom m end ed if using m ethylene blu e
Isosu lfan blu e is a rosaniline d ye of the trip henyl- d u ring a SLN B p roced u re.
m ethane typ e, that is, a 2,5-d isu lfonated isom er of p atent It is notew orthy that a significantly higher rate of total
blu e d ye. Isosu lfan blu e d ye is the only d ye ap p roved by nu m ber of com p lications occu rs in those p atients w ho
the Food and Dru g Ad m inistration in the United States for u nd erw ent a comp lete lym p h nod e d issection (23.2%) after
the visu alization of lym p hatics. Ad verse reactions to blu e SLN B. There is a higher risk of com p lications associated
d ye have been rep orted w ithin a few m inu tes or u p to an w ith ingu inal nod e site (51.2%) com p ared to neck or axil-
hou r after injection. Reactions range from m ild allergic lary sites (10% and 20%, resp ectively). After a sentinel nod e
reactions w ith hives (so-called “blu e hives”) and erythem a biop sy alone in the axilla or groin, a total of 14 (0.7%) of
to angioneu rotic ed em a w ith or w ithou t laryngosp asm 2,083 p atients d evelop ed som e d egree of lym phed em a.
and card iovascu lar collap se. Other rep orted sym p tom s Lym p hed em a w as also m ore com m on for p atients w ho
inclu d e angioed em a, rash, gastrointestinal d istress, p u l- u nd erw ent a com plete ingu inal lym ph nod e d issection
m onary ed em a, and card iac arrhythm ias. Ad d itionally, com p ared to a com p lete axillary lym p h nod e d issection
p atients m ay ap p ear to be cyanotic, having a slight ashen (ALN D; 31.5% vs. 4.6%, p 0.0001) (3).
and / or p ale blu e color to their skin as d ye d rains from the N evertheless, lym p h nod e d issection p rovid es d u rable
lym p hatics into the venou s system and cap illary bed s. The regional control for m ost patients w ith lym ph nod e m etas-
tru e incid ence of reactions to this blu e d ye is u nknow n, tases. Extrap olating from historic d ata com p aring thera-
bu t is generally rep orted to be in the range of 0% to 2.0% p eu tic lym p h nod e d issection, p erform ed for p atients w ith
(3,5–9). clinically evid ent regional lymphad enopathy, to elective
The p atient shou ld be m ad e aw are of this rare bu t lymph nod e d issection provid es rationale for surgical man-
seriou s com p lication of blu e d ye injection, w hich is agement of regional lymph nod e involvement w hen there is
attribu table to an im m u n oglobu lin E–m ed iated reaction. occult, rather than grossly evid ent, disease. Bulky adenopa-
It is im p ortant to have clear com m u nication w ith th e thy often grow s to the point w here large lymph nodes
an esthesiology team abou t p ossible sym p tom s. Th e an es- coalesce into a matted mass that may become fixed to sur-
thesiologist shou ld establish a p reinjection Sp O 2 baseline rounding structures, such as the thoracodorsal neurovascu-
and verify ad equ ate oxygenation and hem od ynam ic sta- lar bund le, long thoracic nerve, axillary vein, and even the
bility p rior to blu e d ye injection . Im m ed iate ch anges in brachial plexus. While attention to anatomic localization and
resp iratory or card iac statu s can th en be d irectly corre- preservation of nerves and vessels is essential, sacrifice of
lated to the injection itself and so carefu l m onitoring of the thoracodorsal neurovascular bundle or long thoracic
the p atien t d u ring and after the blu e d ye in jection is crit- nerve may be necessarily for complete extirpation. Compli-
ical. Managem ent is su p p ortive, and p atients u su ally cations associated w ith therapeutic lymphad enectomy far
resp ond to oxygen ation and flu id resu scitation. Cer- outweigh those seen with elective lymphad enectomy: 61%
tainly, rap id ch anges in the p atien t’s statu s shou ld n ot be compared to 39% (13). Local wound complications were
falsely attribu ted to the blu e d ye injection, and other p os- most common although the incid ence of lymphedema w as
sible cau sative factors that m ay d ecrease oxygenation or higher in the therapeutic group (23%) than in the elective
cau se tachycard ia an d / or h yp otension shou ld be kep t in group (10%) as w ell.
the d ifferen tial d iagn osis w ith su ch ep isod es. Som e h ave The overall com p lication rate w ith regional lym -
consid ered the u se of p rop h ylactic histam in e blockad e p had enectom y is relatively high, bu t m ajor and life-
p rior to intraop erative m ap p ing, bu t this is not cu rrently threatenin g p roblem s are rare. Su rgical m orbid ity after
rou tine p ractice (9). lym p had enectom y is w ell d escribed (14–17). Com m on ly
There are som e su rgeons w ho have su bstitu ted the u se rep orted rates of overall com p lications are in the 25%
of m ethylene blu e d ye for isosu lfan blu e d ye as the m ap - range. Most p atients exp erience w ou nd -related , short-term
issues common to all sites of nodal dissection. Meticulous d em onstrate im p roved resu lts (com p lications of any kind )
surgical technique may ameliorate some superficial surgical w ith cefazolin com p ared to p lacebo for ingu inal lym p h
site infections: careful placement of surgical incisions, avoid - nod e d issection (69% com pared to 62%, respectively) (28).
ance of nonviable skin flap s, and p revention of w ou nd In a contemporary series, 19% of patients had a significant
contamination/ infection. w ou nd complication, either d ehiscence or infection, requir-
There are sp ecific com p lications associated w ith the ing IV antibiotics or op erative m anagem ent. Risk factors for
variou s sites of lym ph nod e d issection. ALN D perform ed w ound complication includ ed obesity and lymphad enec-
for m elanom a is som ew hat d ifferent from the proced ure tom y d one for p alp able d isease (16).
d one for breast cancer, althou gh reported com plications are Serom as are com m only seen p ostop eratively and can
sim ilar. Becau se the proced u re usually inclu d es d issection u su ally be m anaged exp ectantly. Drainage is ap propriate if
of level III nod es in ad d ition to levels I and II, ad d itional the serom a is infected . Postop erative groin lym phoceles are
morbid ity m ay be ascribed to a d eeper d issection and tran- largely caused by the transection of lym phatic channels
section of the p ectoralis m inor m u scle in som e p atients. w ithou t ad equ ate ligation d u ring lym p had enectom y. As a
H ow ever, ad ju vant rad iation therapy is rarely p rescribed resu lt, the p otential sp ace from the site of d issection fills
for melanom a w hile its u se is som ew hat m ore com m on, w ith p rotein-rich lym p hatic flu id , w hich is d evoid of clot-
even if only d irected to the breast/ chest w all field , for ting factors. Lym p hoceles are at risk for infection or sponta-
breast cancer, p otentially changing the profile of p ostop era- neou s d rainage. The m anagem ent of groin lym phoceles is
tive com p lications. Overall com plication rates, inclu d ing d ifficu lt since recu rrence rates are rep orted to be as high as
incid ence of w ou nd infection, serom a, num bness, and lym - 50%. Treatm ent op tions range from exp ectant m anagem ent
phed em a, range from 20% to 47% (3,18). The incid ence of (observation), antibiotics, asp iration w ith com pression,
lym p hed em a ranges from 10% to m ore than 50% (19,20). sclerotherap y (instillation of tetracycline or d oxycycline or
Sentinel node biopsy for head and neck melanomas have bleom ycin), and argon cau terization, to su rgical resection
been associated with mapping to multiple nodal basins and of the lym p hocele cavity, follow ed by su tu re closure/ cov-
w ith a higher rate of false-negative results (21–23). With erage w ith local flap s. While lym p hoceles are seen around
mod ified rad ical neck d issections, often includ ing superfi- the fem oral vessels follow ing any p roced u res, they are
cial parotid ectomy, postoperative com plications are seen in m u ch m ore com m on follow ing lym p had enectom y than
approximately 10% of patients (3,18). SLNB or completion arterial reconstru ction p roced u res (u p to 49% com p ared to
lymphadenectomy in this area carries an overall low er risk u p to 8%). Im m u nosu p p ression, malnu trition, d iabetes
of infection, skin necrosis/ d ehiscence, skin necrosis, and m ellitu s, and u nd erlying chronic illness have been fou nd to
lymphedema, but risk of injury to cranial nerves, particu- be highly associated w ith com p licated w ou nd healing (29).
larly the facial nerve when operating in the periparotid area, The u se of intraop erative lym p hatic m ap p ing w ith isosu l-
must be remembered (24). Familiarity w ith unusual, or less fan blu e d ye to sp ecifically id entify d am aged lym p hatic
common, d rainage patterns is important since lymphatic channels has been d escribed and found to be helpful in
flow patterns includ e accessible nod al basins such as the select cases w hen an op erative ap p roach is d eem ed neces-
popliteal (25) and the epitrochlear (26) nodal basins. sary. Injection of blu e d ye into the d istal extrem ity (i.e.,
Described techniques and surgeon preferences for near circum ferential injection of d ye at the ankle) is m ad e
superficial (and d eep) inguinal lymph nod e d issection vary follow ing exp osu re of the lym p hocele cavity; id entification
w id ely. Deep inguinal d issection, in ad d ition to superficial of lymp hatics for ligation is typ ically m ad e 10 to 15 m in-
ingu inal d issection, is used selectively and most commonly u tes p ostinjection. Obliteration of d ead sp ace w ith m u ltiple
performed in the setting of enlarged iliac nod es on p reoper- layers of absorbable m onofilam ent su tu re or local m uscle
ative cross-sectional imaging and in cases in w hich Clo- flap is an im p ortant ad ju nct (30).
quet’s nod e is fou nd to contain metastatic d isease. Incisions Lym phed em a represents one of the m ost com m on long-
range from obliquely oriented incisions to those that cross term com p lications follow ing rad ical lym p had enop athy
the inguinal crease in a “lazy-S” or inverted hockey stick and is seen in ap p roxim ately 30% of p atients, thou gh it is
fashion, though the oblique incisions are thought to be more noted to be m ore com m on follow ing groin d issection than
prone to complication. Some su rgeons employ d iscontigu - axillary lym p had enectom y. Old er age and obesity are
ous incisions for the d eep (iliac/ obturator) d issection to often cited as risk factors for lym p hed em a. While som e
allow for preservation of the inguinal ligament and cases of lym p hed em a are m ild or su bclinical, lym p hed em a
d ecrease the risk of hernia d evelopment. Drains are rou- w ith associated intrad erm al fibrosis lead s to p rom inent
tinely employed , though a sartorius muscle flap for cover- skin and soft-tissu e changes. Measu rem ents of girth and
age of the exposed femoral vessels is u sed on a more volu m e of the affected lim b are cond u cted , and classically,
selective basis. Classically, the saphenous vein is ligated a m axim u m girth d ifference of 2 cm or m ore or a volu m e
d uring the course of d issection, though there are some sur- d ifference of 200 m L or m ore, w hen com p ared to the con-
geons w ho preserve the structure because they believe that tralateral lim b, is consid ered d iagnostic of lym phed ema
d oing so d ecreases the risk of lymphed ema (27). (31). Prevention of low er extrem ity lym p hed em a is em piric
Most su rgeons u se rou tine p eriop erative antibiotics, and , m ost im p ortantly, inclu d es m easu res taken to prevent
thou gh a sm all p rosp ective rand om ized trial d id not w ou nd in fection . With w ou n d infection, there can be
increased fibrosis of the soft tissu es in the groin and su bse- u sed in the m anagem ent of sarcom as. Com bining surgical
qu ent obliteration of m icroscop ic lym phatics, lead ing to resection w ith other treatm ents—u su ally rad iation, and
lym phed em a. Becau se lym phed em a itself pred isposes to occasionally cytotoxic chem otherap y or other system ic
infection, a viciou s cycle of infection (u su ally in the form of agents—has the p otential to im p rove ou tcom es com pared
cellu litis) and w orsening lym phed ema can ensue. to resection alone bu t can also lead to increased com p lica-
Postoperative m anagem ent w ith elevation and com- tions as w ell. Minimizing the com p lications associated
pression is routine. Patients u nd ergoing groin d issection are w ith sarcom a su rgery starts by ap p rop riate selection of
measured preoperatively for fitted compression garments cand id ates for m u ltim od ality therap y, bu t it also d epend s
(25 to 40 mm H g) as a pre-emptive treatment measu re. For on m eticu lou s techniqu e d u ring the p roced u re.
patients w ith established lymphed ema, d econgestive thera-
pies su ch as manual lymph d rainage techniqu es are ■ Complications of surgical resection
employed w ith reasonable results (59% and 68% red uction for truncal or extremity sarcomas
in lym phed em a volum e for u pp er and low er extrem ities,
respectively) (32). Several components make up the treat- Most soft-tissu e sarcom as are p rim arily treated w ith surgi-
ment phase: skin and nail care, manual lymph d rainage, cal resection. Extrem ity sarcom as shou ld be ap p roached
compression band aging, and therapeutic exercise (20). w ith a lim b-sparing ap proach to achieve local control w ith
Sequential compression d evices as w ell as massage therapy, m inim al m orbid ity, thou gh am p u tation shou ld be consid -
thought to w ork by m imicking the natural pumping action ered in cases w ith m ajor neu rovascu lar involvem ent, bony
of musculature, are controversial since evid ence from a involvem ent, or extensive soft-tissu e/ skin involvem ent.
Cochrane systematic review suggests no benefit above the Although som e sm all or su perficial high-grad e sarcom as in
use of compression (33). There are little d ata to su pport the favorable locations can be treated su ccessfu lly w ith resec-
use of d iuretics for the treatment or p revention of lym- tion alone, m ost soft tissu e sarcom as of the extrem ity are
phed ema. treated w ith a lim b-sp aring ap proach using a com bination
of su rgical resection and rad iation therap y. Althou gh rad ia-
tion low ers recu rrence rates, it can increase the com p lica-
■ SOFT-TISSUE SARCOMAS tions of su rgery. Rad iation can be ad m inistered either
■ Introduction before or after resection, and the com p lication profile
varies accord ing to the tim ing of rad iation. In a rand om -
Like m elanom a, soft-tissu e sarcom as can occur anyw here ized trial, p atients w ho received p reop erative rad iation
in the bod y and the com p lications associated w ith their w ere statistically significantly m ore likely to have w ound
surgical treatm ent vary w ith their anatom ic site. Any and com p lications than those received rad iation after su rgery
all of the com p lications associated w ith soft-tissu e su rgery (35% vs. 17%, p 0.01) (34) (Table 45.1). Overall survival was
for other m alignancies can occur d uring and after resection not significantly different betw een the two groups. Other
of sarcom a as w ell. Multimod ality therapy is frequ ently modalities used have included postoperative brachytherapy
Table 4 5 .1 Wo u n d com p lica t ion s in a r a n d om iz e d t r ia l of p r e op e r a t ive

ve r s u s p o s t o p e r a t ive r a d ia t io n fo r p a t ie n t s w it h r e s e ct a b le
e xt r e m it y s a r co m a s
Preoperative (n 88) Postoperative (n 94)

Wound complications
Yesa 31 (35%) 16 (17%)
Secondary operation for wound repair 14 (45%) 5 (31%)
Invasive procedure for wound managementb 5 (16%) 4 (25%)
Deep wound packing deep to dermis in area of wound 11 (35%) 7 (44%)
at least 2 cm with or without prolonged dressings
6 weeks from wound breakdownc
Readmission for wound cared 1 (3%) 0
No complications 57 (65%) 78 (83%)
a
p 0.01 for yes versus no.
b
Without secondary operation.
c
Without secondary operation or invasive procedure.
d
Without secondary operation, invasive procedure, deep wound packing, or prolonged dressing.
From O’Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs:
a randomised trial. Lancet 2002;359(9325):2235–2241, with permission.
as a means of d elivering rad iation via afterload ing catheters p rop er su p p ort and w ork w ith a rehabilitation m ed icine
placed into the op erative field . In selected patients, there sp ecialist, p atients can have good fu nction, especially w ith
w as a d em onstrated im p roved local d isease-free su rvival m od ern p rosthetic d evices and extensive rehabilitation and
(com p ared to resection alone) w ith a shorter cou rse of training. Unfortu nately, am p u tation lead s to im m obility
w ell-tolerated treatm ents. The entire rad iation d ose cou ld and a severe d ecline in fu nction for m any p atients. A p rob-
be ad m inistered in 4 to 6 d ays, com p ared to a typ ical 6- lem atic com p lication of am p u tation is the so-called p han-
w eek cou rse for external beam rad iation, bu t w ou nd heal- tom p ain, a series of p ainfu l sensations em anating from
ing w as im p aired if load ing w as d one too early in the the extrem ity’s transected nerves and p erceived as if the
p ostop erative p eriod (35). Recu rrences follow ing p rior extrem ity w ere still in p lace. Rem arkably little is know n
lim b-sp aring p roced u res often requ ire am p u tation for abou t how to p revent or treat this com p lication. Phantom
local control. p ain is m ore frequ ent and severe w ith m ore p roxim al
Com p lications can ad versely affect the cosm etic, fu nc- am p u tations bu t tend s to su bsid e over tim e. In view of
tional, and qu ality-of-life outcom es after sarcom a su rgery that consid eration, m ost m anagem ent strategies aim at
(36). One significant long-term com plication of rad iation is p rovid ing short-term relief throu gh the u se of gabap entin,
pathologic fractu re of the und erlying bone since this com - tricyclic antid ep ressants, and anxiolytics. One rand om -
plication is d ifficu lt to treat and associated w ith a very high ized trial su ggested that d extrom ethorp han in high d oses
risk of su bsequ ent amp utation (37,38). The risk of p atho- cou ld m inim ize the d evelop m ent and intensity of p han-
logic fractu re increases w ith the rad iation d ose d elivered to tom p ain (45).
the bone and w ith extensive stripping of the periosteu m of
the bone (if d one as part of the su rgical resection). Prop hy- ■ Complications of resections
lactic p lacem ent of intram ed u llary nails in w eight-bearing
for retroperitoneal sarcomas
long bones has been ad vocated by som e to prevent this
com p lication. Irrad iated areas of the trunk can p resent a Managem ent of retrop eritoneal and intra-abd om inal sarco-
major challenge for reconstru ction since large soft-tissue m as is d ep end ent on com p lete su rgical resection, though
defects are associated w ith delayed healing and may require location and p roxim ity to visceral organs can frequ ently
com plex m yocu taneous flaps for closure. p reclu d e w id e m argins or m icroscopically clear m argins.
Patients w ho und ergo neoad ju vant (p reoperative) Differential d iagnosis of retroperitoneal m asses includ es
chem otherap y m ay be m ore likely to have su rgical com pli- lym p hom a, m etastatic testes cancer (lym p had enopathy),
cations. This ap p ears to be p articularly tru e if both or neu roend ocrine cancers. Ap p rop riate preoperative
chem otherap y and rad iation are given together prior to w orku p should be und ertaken w hen d iagnosis is in qu es-
resection (39). Com bined , chem otherap y and rad iation tion to avoid u nexp ected intraop erative find ings. To avoid
present both acu te and chronic w ound -healing p roblem s p recipitating a hyp ertensive crisis if a retroperitoneal
that m u st be consid ered in the surgical planning, both for tu m or proves to be a functional extra-ad renal pheochrom o-
resection and for reconstruction (40). Even in the era of cytom a rather than sarcom a, a high ind ex of su spicion
molecu larly targeted agents, w hich are generally better tol- need s to be m aintained if p reop erative d iagnosis is not
erated than cytotoxic chem otherap y agents, d ue consid era- established and com p lete end ocrine w orku p is not d one.
tion m u st be given to potential com plications of treatm ent, Since en bloc resection of one or m ore visceral organs is
w hich can lead to an u rgent need for su rgical intervention often necessary for comp lete resection, carefu l exam ination
(41). The u se of im atinib (Gleevec™) for the treatm ent of of cross-sectional im aging is of p aram ou nt im portance.
gastrointestinal strom al tum ors (GISTs) has becom e a para- Even w hen there is no obviou s involvem ent of bow el itself,
d igm of targeted therap ies. Current ind ications for u se extensive tu m or involvem ent of the m esentery and vascu -
includ e m etastatic tu m ors and ad ju vant treatm ent of high- lar su p p ly to the bow el m ay necessitate resection. Com pli-
risk GISTs (42). Seriou s ad verse events reported w ith the cation rates after resection are high, esp ecially if there is
use of im atinib and other tyrosine kinase inhibitors inclu d e concom itant resection of sp leen, p ancreas, and / or colon,
hem orrhage, and less com m only, bow el perforation and all ad d ing to the likelihood of site-sp ecific m orbid ity. Com -
tu m or ru p tu re. Its u se is associated w ith anastom otic leaks m only, nep hrectom y is requ ired d u e to encasem ent of the
and d elayed w ou ld healing follow ing su rgical resection kid ney or renal vessels by tu m or or becau se of d ense
and m ay be d u e to hem atologic changes and im m u nosu p - ad herence to the renal cap su le. Rad iograp hic evid ence of
pression w ith long-term u se of su ch d rugs. bilateral renal function shou ld be ensured prior to resec-
tion, bu t concom itant nep hrectom y is u su ally w ell toler-
ated (46). Partial resection of retrop eritoneal sarcom as is
■ Complications of amputation associated w ith su rvival ou tcom es that are little or no bet-
With p rop er selection of p atients for lim b-salvage therap y, ter than no resection at all (47). Thu s, p artial resection con-
amp u tation is infrequently necessary. Although it seem s veys all the m orbid ity w ithout any of the therapeutic
obviou s that am p u tation is associated w ith a greater d is- benefit and shou ld only be consid ered in select cases for
ru p tion of fu nction and qu ality of life than lim b-sp aring p alliation w hen bu lk of d isease results in bow el obstru c-
proced u res, qu ality-of-life stud ies are sp arse (43,44). With tion or end -organ failu re.
Rad iation to the retrop eritoneu m p laces viscera at 13. Ingvar C, Erichsen C, Jonsson PE. Morbid ity follow ing p rop hylactic
and therap eu tic lym ph nod e d issection for m elanom a—a com p arison.
risk, an d ad equ ate d oses of extern al beam rad iation for Tumori 1984;70(6):529–533.
treatm ent are frequ ently accom p anied by u naccep table 14. Urist MM, Mad d ox WA, Kenned y JE, et al. Patient risk factors and su r-
acu te and late toxicities. Effects of rad iation on sm all gical m orbid ity after regional lym p had enectom y in 204 m elanom a
patients. Cancer 1983;51(11):2152–2156.
bow el inclu d e fistu la form ation, strictu re, u lceration w ith 15. Tonou chi H , Ohm ori Y, Kobayashi M, et al. Op erative m orbid ity associ-
hem orrhage, an d in tractable obstru ction, all of w hich can ated w ith groin d issections. Surg Today 2004;34(5):413–418.
be p articu larly m orbid and even p otentially fatal. Use of 16. Sabel MS, Griffith KA, Arora A, et al. Ingu inal nod e d issection for
m elanom a in the era of sentinel lym p h nod e biop sy. Surgery
conform al techn iqu es and / or p reop erative rad iation 2007;141(6):728–735.
have been u sed to d ecrease the risks of m orbid ity since 17. Meyer T, Merkel S, Gohl J, et al. Lym p h nod e d issection for clinically
nearby stru ctu res are p rotected , bu t have not m et w ith evid ent lym p h nod e m etastases of m alignant m elanom a. Eur J Surg
Oncol 2002;28(4):424–430.
im p roved ou tcom es in term s of local control (48) or over- 18. Serp ell JW, Carne PW, Bailey M. Rad ical lym p h nod e d issection for
all su rvival (49). m elanom a. ANZ J Surg 2003;73(5):294–299.
19. Starritt EC, Joseph D, McKinnon JG, et al. Lym p hed em a after com p lete
axillary nod e d issection for m elanom a: assessm ent u sing a new, objec-
■ CONCLUSION tive d efinition. Ann Surg 2004;240(5):866–874.
20. Law end a BD, Mond ry TE, Johnstone PA. Lym p hed em a: a p rim er on
the id entification and m anagem ent of a chronic cond ition in oncologic
Com p lications of soft-tissue tu m or surgery can be m ini- treatm ent. CA Cancer J Clin 2009;59(1):8–24.
mized by good techniqu e and preoperative preparation. 21. Carlson GW, Page AJ, Cohen C, et al. Regional recurrence after negative
Sp ecific op erative risks w ith soft-tissu e tu m ors are u su ally sentinel lymph nod e biopsy for melanoma. Ann Surg 2008;248(3):378–386.
22. Fincher TR, O’Brien JC, McCarty TM, et al. Patterns of d rainage and
related to the tu m or ’s location and extent of resection. Post- recu rrence follow ing sentinel lym p h nod e biop sy for cu taneou s
op erative issu es can range from su p erficial su rgical site m elanom a of the head and neck. Arch Otolaryngol Head Neck Surg 2004;
infections to m ore serious and chronic com plications. Ju d i- 130(7):844–848.
23. d e Wilt JH , Thom p son JF, Uren RF, et al. Correlation betw een p reop era-
ciou s u se of m u ltim od ality therap y, com bined w ith ap p ro- tive lym p hoscintigrap hy and m etastatic nod al d isease sites in 362
priately bu t not excessively rad ical su rgery, strikes the patients w ith cu taneous m elanom as of the head and neck. Ann Surg
proper balance betw een tu m or control and avoid ance of 2004;239(4):544–552.
24. Picon AI, Coit DG, Shaha AR, et al. Sentinel lym p h nod e biop sy for
com plications and highlights the im portant role the su rgi- cu taneou s head and neck m elanom a: m ap p ing the p arotid gland . Ann
cal oncologist plays in the m anagem ent of soft-tissu e Surg Oncol 2006.
malignancies. 25. Sholar A, Martin RC II, McMasters KM. Pop liteal lym p h nod e d issec-
tion. Ann Surg Oncol 2005;12(2):189–193.
26. Tanabe KK. Lym phatic m ap p ing and ep itrochlear lym p h nod e d issec-
tion for m elanom a. Surgery 1997;121(1):102–104.
■ REFERENCES 27. Zhang SH , Sood AK, Sorosky JI, et al. Preservation of the sap henou s
vein d u ring ingu inal lym p had enectom y d ecreases m orbid ity in
1. Dresel A, Kuhn JA, McCarty TM. Sentinel nod e biop sy site u sed as fu ll patients w ith carcinom a of the vu lva. Cancer 2000;89(7):1520–1525.
thickness skin graft d onor for cu taneou s m elanom a. Am J Surg 2002; 28. Coit DG, Peters M, Brennan MF. A p rosp ective rand om ized trial of
184(2):176–178. perioperative cefazolin treatm ent in axillary and groin d issection. Arch
2. Morton DL, Thom pson JF, Cochran AJ, et al. Sentinel-nod e biop sy or Surg 1991;126(11):1366–1371; d iscu ssion 1371–1372.
nod al observation in m elanom a. N Engl J Med 2006;355(13):1307–1317. 29. Stad elm ann WK, Digenis AG, Tobin GR. Im p ed im ents to w ou nd heal-
3. Wrightson WR, Wong SL, Ed w ard s MJ, et al. Com p lications associated ing. Am J Surg 1998;176(2A Su p p l):39S–47S.
w ith sentinel lym p h nod e biop sy for m elanom a. Ann Surg Oncol 30. Stad elm ann WK, Tobin GR. Su ccessfu l treatm ent of 19 consecu tive
2003;10(6):676–680. groin lym p hoceles w ith the assistance of intraop erative lym p hatic
4. Jansen L, N iew eg OE, Peterse JL, et al. Reliability of sentinel lym p h m ap p ing. Plast Reconstr Surg 2002;109(4):1274–1280.
nod e biopsy for staging m elanom a. Br J Surg 2000;87(4):484–489. 31. Arm er JM, Stew art BR. A com p arison of fou r d iagnostic criteria for
5. Wrone DA, Tanabe KK, Cosim i AB, et al. Lym p hed em a after sentinel lym p hed em a in a p ost-breast cancer p op u lation. Lymphat Res Biol
lym ph nod e biop sy for cu taneou s m elanom a: a rep ort of 5 cases. Arch 2005;3(4):208–217.
Dermatol 2000;136(4):511–514. 32. Ko DS, Lerner R, Klose G, et al. Effective treatm ent of lym p hed em a of
6. Leong SP, Donegan E, H effernon W, et al. Ad verse reactions to isosu l- the extrem ities. Arch Surg 1998;133(4):452–458.
fan blue d uring selective sentinel lym ph nod e d issection in m elanom a. 33. Bad ger C, Preston N , Seers K, et al. Physical therap ies for red u cing and
Ann Surg Oncol 2000;7(5):361–366. controlling lym p hoed em a of the lim bs. Cochrane Database Syst Rev
7. Keller B, Yaw alkar N , Pichler C, et al. H yp ersensitivity reaction against 2004;(4):CD003141.
p atent blue d u ring sentinel lym p h nod e rem oval in three m elanom a 34. O’Su llivan B, Davis AM, Tu rcotte R, et al. Preop erative versu s p ostop -
p atients. Am J Surg 2007;193(1):122–124. erative rad iotherapy in soft-tissue sarcom a of the lim bs: a rand om ised
8. Morton DL, Cochran AJ, Thom p son JF, et al. Sentinel nod e biop sy for trial. Lancet 2002;359(9325):2235–2241.
early-stage m elanom a: accu racy and m orbid ity in MSLT-I, an interna- 35. Pisters PW, H arrison LB, Leu ng DH , et al. Long-term resu lts of a
tional m u lticenter trial. Ann Surg 2005;242(3):302–311; d iscussion prosp ective rand om ized trial of ad ju vant brachytherapy in soft tissu e
311–313. sarcom a. J Clin Oncol 1996;14(3):859–868.
9. Cim m ino VM, Brow n AC, Szocik JF, et al. Allergic reactions to isosu lfan 36. Davis AM, O’Su llivan B, Bell RS, et al. Fu nction and health statu s ou t-
blu e d u ring sentinel nod e biop sy—a com m on event. Surgery 2001; com es in a rand om ized trial com paring preoperative and postopera-
130(3):439–442. tive rad iotherap y in extrem ity soft tissu e sarcom a. J Clin Oncol
10. Strad ling B, Aranha G, Gabram S. Ad verse skin lesions after m ethylene 2002;20(22):4472–4477.
blu e injections for sentinel lym p h nod e localization. Am J Surg 37. Lin PP, Boland PJ, H ealey JH . Treatm ent of fem oral fractu res after irra-
2002;184(4):350–352. d iation. Clin Orthop Relat Res 1998(352):168–178.
11. Zakaria S, H oskin TL, Degnim AC. Safety and technical su ccess of 38. Lin PP, Schu pak KD, Boland PJ, et al. Pathologic fem oral fractu re after
m ethylene blu e d ye for lym p hatic m ap p ing in breast cancer. Am J Surg periosteal excision and rad iation for the treatm ent of soft tissu e sar-
2008;196(2):228–233. com a. Cancer 1998;82(12):2356–2365.
12. Bleicher RJ, Kloth DD, Robinson D, et al. Inflam m atory cu taneou s 39. DeLaney TF, Spiro IJ, Su it H D, et al. N eoad ju vant chem otherap y and
ad verse effects of m ethylene blu e d ye injection for lym p hatic m ap - rad iotherapy for large extrem ity soft-tissu e sarcom as. Int J Radiat Oncol
p ing/ sentinel lym phad enectom y. J Surg Oncol 2009;99(6):356–360. Biol Phys 2003;56(4):1117–1127.
40. Peat BG, Bell RS, Davis A, et al. Wou nd -healing com p lications after 45. Ben Abraham R, Marou ani N, Weinbrou m AA. Dextrom ethorphan m it-
soft-tissu e sarcom a su rgery. Plast Reconstr Surg 1994;93(5):980–987. igates phantom pain in cancer am putees. Ann Surg Oncol 2003;10(3):
41. Rutkow ski P, Ru ka W. Em ergency su rgery in the era of m olecular treat- 268–274.
m ent of solid tu m ou rs. Lancet Oncol 2009;10(2):157–163. 46. Ru sso P, Kim Y, Ravind ran S, et al. N ep hrectom y d u ring op erative
42. Dem atteo RP, Ballm an KV, Antonescu CR, et al. Ad ju vant im atinib m anagem ent of retrop eritoneal sarcom a. Ann Surg Oncol 1997;4(5):
m esylate after resection of localised , p rim ary gastrointestinal strom al 421–424.
tum ou r: a rand om ised , d ou ble-blind , p lacebo-controlled trial. Lancet 47. H eslin MJ, Lew is JJ, N ad ler E, et al. Prognostic factors associated w ith
2009;373(9669):1097–1104. long-term su rvival for retroperitoneal sarcom a: im plications for m an-
43. Gerrand CH , Wund er JS, Kand el RA, et al. The influ ence of anatom ic agem ent. J Clin Oncol 1997;15(8):2832–2839.
location on functional ou tcom e in low er-extrem ity soft-tissu e sarcom a. 48. Ballo MT, Zagars GK, Pollock RE, et al. Retrop eritoneal soft tissu e sar-
Ann Surg Oncol 2004;11(5):476–482. com a: an analysis of rad iation and su rgical treatm ent. Int J Radiat Oncol
44. Chang AE, Steinberg SM, Cu lnane M, et al. Fu nctional and p sychoso- Biol Phys 2007;67(1):158–163.
cial effects of m u ltim od ality lim b-sp aring therap y in p atients w ith soft 49. Feng M, Mu rphy J, Griffith KA, et al. Long-term ou tcom es after rad io-
tissu e sarcom as. J Clin Oncol 1989;7(9):1217–1228. therapy for retrop eritoneal and d eep tru ncal sarcom a. Int J Radiat Oncol
Biol Phys 2007;69(1):103–110.
CHAPTER
46
Complications of Lymphadenectomy
Alliric I. Willis and J effrey F. Moley
Lym p had enectom y is an integral com p onent of su rgical complication rate from axillary d issection is reported to be
oncology for the d iagnosis, staging, and regional control of as high as 25% to 30%, and includ es lymp hed ema, numb-
variou s cancers. As our u nd erstand ing of lym phatic m etas- ness, and chronic pain (4).
tasis has increased , the benefits of extensive lym phad enec- The anatom ical bou nd aries and stru ctu res of im p or-
tom y for certain cancers have been appreciated . H ow ever, tance in an axillary d issection are the lateral bord ers of the
lym phad enectom y can resu lt in significant m orbid ity from p ectoralis mu scles and the chest w all along w hich lies the
com p lications related to the d isru p tion of the lym p hatic long thoracic nerve m ed ially, the lateral bord er of the latis-
system , inju ry of su rrou nd ing stru ctu res, w ou nd com p lica- sim u s d orsi m u scle laterally, the axillary vein su periorly,
tions, and fu nctional imp airm ent. An appreciation of the the u p p er ou ter qu ad rant breast tissu e inferiorly, the thora-
benefits of less extensive lym ph nod e d issections to stage cod orsal neu rovascu lar bu nd le p osteriorly, and the axillary
certain cancers has resu lted in red u ctions in the frequ ency fascia anteriorly. Carefu l d issection w ith attention to the
and severity of com p lications. id entification of stru ctu res is essential to m inim ize the risk
The m ost significant p arad igm shift in the su rgical eval- of com p lications. Entering the axillary fascia inferiorly can
u ation for lym phatic m etastases has been the d evelop m ent help avoid inju ry to the axillary vein. Carefu l d issection
of sentinel lym p h nod e biopsy (SLN B). This techniqu e has med ially along the pectoralis m u scles can help avoid injur-
been m ost w id ely applied and valid ated in m elanom a and ing the p ectoralis neu rovascu lar bu nd le. Su p eriorly, care
breast cancer (1,2). SLN B involves the injection of blu e d ye shou ld be taken to avoid skeletonizing the axillary vein to
and / or rad ioactive tracer at the site of interest and the d is- avoid the risk of vessel inju ry as w ell as to red u ce the risk
section and excision of the sentinel lym ph nod e(s). The sen- of lym p hed em a.
tinel lym ph nod es are the first to receive the tracer or d ye, The intercostobrachial nerve can u su ally be id entified
and the first, in theory, to receive lym ph nod e m etastases. cou rsing across the low er axilla. The axillary contents m ay
Sentinel nod es inclu d e all visibly blu e lym p h nod es and all be d ivid ed to p ass over or u nd er the intercostobrachial
lym ph nod es w ith high gam m a probe counts (3). nerve to p reserve it. H ow ever, if it is not p ossible to d issect
This chapter will focus on complications of lymphad enec- the nerve free of tu m or, then it can be sacrificed , w hich
tomy by region. resu lts in the loss of sensation in the u p p er, inner arm .
When no attem p t is m ad e to sp are the intercostobrachial
nerve d u ring axillary d issection, the incid ence of arm
■ AXILLARY
nu m bness has been rep orted to be as high as 68% to 81%
Axillary lymph nod e d issection is an important component (4,5).
of the surgical staging of breast cancer as a part of both One of the m ost com m on com p lications of axillary d is-
breast conserving therapy and mastectomy. Axillary lymp h section is serom a form ation or lym p horrhea, w hich refers
nod e d issection is also an important part of regional staging to p ersistent d rainage of axillary lym p hatic flu id . This can
and control of m elanom a in locations that may d rain into resu lt from transection of lym p hatic vessels, the u se of elec-
the axillary lym p h nod es, includ ing the tru nk and u pper trocau tery, filling of the d ead sp ace rem aining after
extremities. Ind ications of axillary d issection includ e rem oval of the axillary contents, and local inflam m atory
biopsy-proven metastatic cancer, clinically positive lym - resp onse (6). Lym p horrhea and serom a form ation are also
phad enop athy in the presence of a d iagnosis of cancer, and associated w ith w ou nd breakd ow n and infection. The
histologically positive sentinel lymph nod es. The long-term rep orted incid ence of serom a form ation after axillary d is-
section ranges from 35% to as high as 97% in breast cancer
p atients (6–8).
Alliric I. Willis: Tem p le University School of Med icine, In a p rosp ective stu d y by Talbot and Magarey, three
Philad elp hia, PA 19140. grou p s of 30 p atients each w ere follow ed p ostop eratively
Jeffrey F. Moley: Washington University School of Med i- after axillary d issection for breast cancer. One grou p m ain-
cine, Saint Louis, MO 63110. tained closed su ction axillary d rainage u ntil the 24-hour
602
Chapter 46 • Complications of Lymphadenectomy 603
d rain outpu t w as 50 m L. This resu lted in an average of the axilla and skin flaps for m od ified rad ical mastectomy. In
9.6 d ays of d rain p lacem ent. The second group had d rains this stud y, a 4-mL d ose of fibrin sealant to the axilla pro-
rem oved 2 d ays after su rgery, regard less of the d rainage d u ced a statistically significant red u ction in d rainage vol-
amou nt. The third grou p had no d rains placed . The resu lts ume and time to drain removal in patients after lumpectomy
of this stu d y d eterm ined that d rain p lacem ent m ad e no sig- and axillary d issection. A 16-m L d ose to the axilla and an
nificant d ifference in the d u ration of serom a form ation fol- 8-m L d ose to the skin flap s also resu lted in a significant
low ing su rgery. The d u ration of serom a accu m ulation that reduction in d rainage volume and time to d rain removal in
cou ld be asp irated after surgery w as 26.6 d ays for grou p 1, mod ified rad ical mastectomy patients (6,9).
25.7 d ays for grou p 2, and 27.9 d ays for group 3. Ad d itional One of the m ost m orbid com p lications of lym p had enec-
analysis show ed that tum or involvem ent of the nod es, the tomy is lym p hed em a. The overall rep orted incid ence of
nu m ber of nod es rem oved , and the type of su rgery p er- lym phed em a in association w ith axillary d issection varies
form ed (lu mp ectom y w ith axillary d issection vs. m od ified from 5% to 80% (10). Cau ses of lym p hed em a inclu d e inju ry
rad ical m astectom y) had no significant effect on serom a to lym p hatics and veins by su rgery, tu m or infiltration of
form ation (8). lym p hatics, and the effects of rad iation therapy that can
Althou gh axillary closed suction d rainage rem ains the cau se fibrosis arou nd lym p hatics. Lym p hed em a can be
stand ard for controlling lym p horrhea after axillary d issec- d efined as acu te p hase, characterized by p itting w hich is
tion and p reventing serom a form ation, efforts have been u su ally resp onsive to com p ression therap y, and chronic
mad e to red u ce the am ou nt of lym phorrhea p rod u ced . In a p hase, w hich is nonp itting and is p oorly responsive to
stu d y by Carcoforo et al. (6), octreotid e, the synthetic com p ression therap y. Tissu es affected by lym p hed em a are
som atostatin analog, w as investigated in the treatm ent of m ore su scep tible to infection if inju red and are m ore d iffi-
lym p horrhea, on the basis of the facts that octreotid e has cu lt to heal (10).
been u sed in the treatm ent of abd om inal and thoracic lym - Velanovich and Szym anski (11) rep orted a quality-of-
phatic leaks, som atostatin recep tors have been fou nd in life stu d y in breast cancer p atients w ith lym phed em a. A
lym p hatic tissu es, and som atostatin has been show n to registry of 827 p atients w ith breast cancer w as evalu ated
red u ce local inflam m atory resp onses w hen given system i- d efining lym p hed em a as m id -hu m eru s or m id -rad iu s cir-
cally. In this p rospective rand om ized trial involving 261 cu m ference 1 cm , m ore than the resp ective circu mference
patients w ho u nd erw ent axillary d issection, 125 p atients of the u ninvolved arm . The incid ence of lym p hed em a w as
w ere treated p ostop eratively w ith octreotid e (0.1 m g su b- m easu red to be 8.3%. A su bset of 101 consecu tive patients
cu taneou sly three tim es d aily for 5 d ays) and comp ared w as evalu ated u sing the qu ality-of-life assessm ent instru -
w ith a control grou p of 136 patients for lym phorrhea ou t- m ent SF-36. Com p arisons w ere m ad e w ithin this stu d y
pu t and serom a form ation. The octreotid e grou p had sig- group am ong patients w ho u nd erw ent breast surgery
nificantly less lym phorrhea (65.4 vs. 94.6 mL) and w ithou t lym p had enectom y, those w ho u nd erw ent lym -
significantly shorter d u ration of lym phorrhea (7.1 vs. 16.7 p had enectom y w ithou t lym p hed em a, and p atients w ith
d ays) than the control grou p. There w as, how ever, no sig- lym p had enectom y and lym p hed em a. This stud y found
nificant d ifference in the length of hospital stay or the that p atients w ith lym p hed em a had statistically signifi-
length of tim e that the axillary d rains w ere kept in place. cantly low er quality-of-life scores in the d om ains of role-
While the w ou nd com plication rate for the control grou p em otional and bod ily p ain, w hile there w ere no significant
w as three tim es greater than that of the octreotid e grou p , d ifferences in scores betw een p atient grou p s that d id not
the overall w ou nd com plication rate w as only 1.5%. The have lym p hed em a. Also, there w ere significantly m ore
rep orted com p lications associated w ith octreotid e w ere p atients w ith lym p hed em a w ho had qu ality-of-life scores
injection-site irritation and gastrointestinal d iscom fort, 1 stand ard d eviation below the national average in the
thou gh none of these resu lted in p atients d iscontinu ing areas of bod ily p ain, m ental health, and general health (11).
treatm ent (6). Octreotid e and new er long-acting versions Axillary lym ph nod e d issection for m elanom a is also
present a p rom ising potential for controlling lym p horrhea associated w ith significant m orbid ity. Wrightson et al. (12)
and serom a form ation; how ever, their cost-effective clinical rep orted the Su nbelt Melanom a Trial, a large-scale, m ulti-
utility rem ains lim ited . institu tional, p rosp ective, rand om ized trial, stu d ying com -
Fibrin sealant, a tissue ad hesive consisting of fibrinogen p lications associated w ith regional lym p h nod e d issection
and throm bin, has been reported to red uce the volu m e of and SLN B for m elanom a. The overall incid ence of com pli-
lym p horrhea after lym phatic d issection. Moore et al. (9) cations associated w ith lym p had enectom y w as 23%. The
rep orted a p hase II, m u lticenter, prospective, parallel, ran- com plication incid ence specifically for axillary d issection
d om ized trial com paring d rainage am ounts and d rain w as 20%. The incid ence of lym p hed em a w ith axillary d is-
placem ent d u ration am ong 79 patients treated w ith fibrin section w as nearly 5% (12). In another stu d y, Serpell et al.
sealant and axillary d rains or w ith stand ard axillary (13) rep orted a p rosp ective stu d y of 64 p atients w ho u nd er-
d rainage. In ad d ition, this trial established a d ose–resp onse w ent 73 lym p had enectom ies, 34 of w hich w ere axillary d is-
cu rve for fibrin sealant. In the treatm ent group s varying sections. The overall incid ence of w ou nd com plications
d oses of fibrin sealant w ere applied just prior to closing the am ong axillary d issections w as 47%, w ith sp ecifically 32%
axilla for lu m p ectom y w ith axillary d issection or closing serom a, 6% w ou nd infection, 6% d elayed healing, and 3%
hem atom a. The incid ence of lym phed em a after axillary d issection group w as found to have significantly more
d issection w as 6% (13). ed em a as d eterm ined by arm circu m ference at the m id -
SLN B is w id ely accepted as an accu rate, m inim ally bicep and antecu bital fossa w hen measu red at a minimu m
invasive technique of assessing axillary lym ph nod e status of 6 months after su rgery. Significantly more axillary d issec-
in patients w ith clinically negative axillary nod es and iso- tion patients complained of arm numbness (81%); how ever,
lated or m ultifocal breast cancer tu m ors in the sam e qu ad - 17% of SLN B patients had complaints of arm nu mbness.
rant. The p remise for this techniqu e is based on the theory The authors note that no attempts w ere mad e to spare the
that the sentinel lym ph nod e, the first lym ph nod e to intercostobrachial nerve. Significantly few er SLN B p atients
receive the blu e d ye m arker or technetium -99 su lfu r colloid had axillary d rains placed (16% vs. 100%). The length of
rad ioactive m arker, is the first lymp h nod e to be involved d rain d uration w as also highly significantly less among
w ith axillary nod al m etastatic d isease. Multiple stu d ies SLN B patients (0.5 vs. 13 d ays for axillary d issection).
that valid ate SLN B as accu rate w ith a low false-negative Eighty-seven percent of SLN B patients had outpatient pro-
rate have been rep orted (1). ced ures and 70% returned to normal activities 3 d ays after
Patients w ith sentinel lym ph nod es positive for cancer surgery versus 100% of axillary d issection patients staying
su bsequ ently u nd ergo a com p letion axillary d issection. overnight and 73% of patients returning to normal activities
The axillary d issection m ay be p erform ed as a second su r- 7 d ays after surgery (4).
gery or d uring the sam e operation if the d iagnosis is m ad e Schrenk et al. (7) rep orted a p rosp ective, nonrand om -
on frozen section or tou ch p rep analysis. An accu racy rate ized trial com p aring 35 SLN B p atients w ith 35 axillary d is-
of 94% in d iagnosing positive sentinel lym ph nod es on section p atients w ith negative nod es. N o SLN B p atients
frozen section w as rep orted by Bu rak et al. (4). Diagnosis had d rains p laced and none requ ired asp iration after su r-
on intraop erative frozen section can p revent the p atient’s gery. All of the axillary d issection p atients had d rains
anxiety associated w ith a second su rgery for axillary d is- p laced , and 43% requ ired asp iration after their d rains
section. H ow ever, the im m u nohistochem ical analysis p er- w ere rem oved . SLN B p atients had no lym p hed em a based
form ed in m elanoma patients cannot be com pleted u p on arm circu m ference before and after su rgery. Axillary
intraop eratively. Those w ho have sentinel nod es negative d issection p atients had a significantly increased arm cir-
for m etastatic d isease d o not requ ire fu rther su rgery and cu m ference in the forearm and u p p er arm after su rgery
can be spared of the risk of com plications associated w ith and a highly significant incid ence of p ostop erative com -
axillary d issection. p laints of lym p hed em a. N one of the SLN B p atients had
SLN B injections for breast cancer p atients m ay be p er- com p laints of nu m bness, w hereas 69% of axillary d issec-
form ed in the retroareolar area or peritum oral. The tion p atients had com p laints of nu m bness after su rgery.
retroareolar injection is based u p on the p rem ise that the SLN B p atients also had significantly few er com p laints of
retroareolar p lexu s of lym p hatics consistently d em on- p ain and restricted arm m obility (7).
strates the d rainage of the breast to the sentinel nod e. Peri- The aforem entioned Su nbelt Melanom a Trial com -
tu m oral injection is p erform ed to d em onstrate d irectly the p ared com p lications of regional lym p had enectom y w ith
lym phatic flow from the site of the tu m or. There is no con- those of SLN B in m elanom a p atients. A highly significant
sensu s regard ing the op tim al site of injection. Suam i et al. d ifference w as fou nd betw een total com p lications w ith
(14) have d em onstrated in a stu d y of the lymp hatic axillary SLN B (4%) versu s axillary d issection (20%). Lym -
anatom y of the breast that w hile the m ajority of the breast p hed em a w as less likely to occu r after SLN B ( 1%) com -
d oes d rain to a sentinel lym ph nod e, as w ould be d em on- p ared to axillary d issection (5%). The overall com p lication
strated by a su bareolar injection, each area of the breast can incid ence w ith SLN B w as nearly 5% (vs. 23% w ith lym -
be d rained by m ore than one first-tier nod e, w hich d oes not p had enectom y). H em atom a/ serom a form ation (2%) and
involve the su bareolar plexus. This m ay contribu te to the w ou nd infection (1%), how ever, w ere m ore com m on
incid ence of false-negative sentinel lym ph nod e biop sies, am ong SLN B p atients (12).
w hich m ay be 5% to 10% in breast cancer patients (14). Schijven et al. (5) rep orted a retrosp ective stu d y of 213
Multiple stud ies have d emonstrated that SLN B signifi- axillary d issection p atients and 180 SLN B p atients w ho
cantly red uces the incid ence of complications associated w ere evalu ated by their answ ers on a qu ality-of-life qu es-
w ith lymphad enectomy. Burak et al. (4) reported a prospec- tionnaire. Axillary d issection p atients had significantly
tive, nonrand omized , controlled stud y of 96 patients in m ore comp laints of p ostop erative p ain, lym phed em a,
w hich they compared 48 patients w ho und erw ent SLNB nu m bness or tingling in the arm and hand , imp aired range
and w ere found to have negative sentinel nod es to 48 of m otion, and im p aired u se of the affected arm (5).
patients w ho u nd erw ent SLN B, w ere found to have positive Though the incid ence of complications is decreased w ith
nod es, and su bsequ ently u nd erw ent axillary d issection. SLNB causes fewer complications than lymph node dissec-
N inety-fou r percent of the patients u nd ergoing axillary d is- tion, however, some complications still occur. One complica-
section had that proced ure d uring the same surgery as the tion specific to SLNB is reaction to the dye-injected. Patent
SLN B based upon positive frozen section d iagnosis. Six per- blue dye is the preferred dye in Europe for SLNB. It has been
cent had a separate proced ure performed because the per- estim ated that nearly 3% of the p opu lation m ay be allergic
manent SLN B specimen w as read as positive. The axillary to patent blue d ye. Patients have been reported to have
reactions ranging from rashes and urticaria to anaphylaxis lym phad enectom y tend to be the rule rather than the
(15,16). In the United States, isosulfan blue is the preferred excep tion, and p atients shou ld be carefu lly informed of
dye marker for SLNB. The incidence of allergic reactions is this p reop eratively. The Su nbelt Melanom a Trial reported a
1.5%, and as many as 1% may have anaphylaxis. In the Sun- 51% incid ence of total comp lications w ith inguinal lym -
belt Melanoma Trial of over 1,600 SLNB, there w ere no cases p had enectom y and an incid ence of nearly 32% for lym -
of reactions to isosulfan blue or technetium (12,15). Radiation p hed em a (12). Serp ell et al. (13) rep orted an overall
safety precautions should be observed w hen using tech- com p lication incid ence of 71% associated w ith ingu inal
netium as a radioactive marker for SLNB. Methylene blue lym p had enectom y for m elanom a w ith a 25% incid ence of
dye has also been popularly received as a marker for SLNB. infection, 25% incid ence of d elayed w ou nd healing, and
In a retrospective study reported by Stradling et al. (17), 5 of 46% incid ence of serom a. The incid ence of lym phed em a
24 consecutive patients had severe erythematous, ulcerated , w as 29% (13).
or necrotic lesions where methylene blue dye was injected In a retrosp ective review from M.D. And erson of 106
intradermally. No complications were associated with intra- ingu inal lym p had enectom y p roced u res in 53 patients w ith
parenchymal injection of methylene blue. invasive p enile cancer, Bevan-Thom as et al. (19) reported
One techniqu e p rop osed to p reserve the lym p hatic an overall com p lication rate of 57%. Prop hylactic and ther-
d rainage of the arm d u ring axillary d issection and possibly ap eu tic d issections had sim ilar com p lication rates of
red u ce the incid ence of lym p hed em a is axillary reverse ap p roxim ately 35%. Palliative d issections had a signifi-
map p ing. This p roced ure, d escribed by Klim berg’s grou p cantly higher incid ence of com p lications at 67% (19).
involves id entifying the lym phatics d raining the arm by Gaarenstroom et al. (20) rep orted a retrosp ective stu d y
injecting blu e d ye subcutaneou sly in the u pper arm . Su b- of 187 ingu inal d issections in 101 p atients for d iagnosed
areolar injection of technetiu m is used to id entify the sen- vu lvar carcinom a. The com p lication rate p er inguinal d is-
tinel lym p h nod e. In this stu d y inclu d ing 220 patients, the section w as 52%. Sp ecific com p lication incid ences noted
axillary reverse m apping lym p hatics d raining the arm w ere lym p hed em a (21%), lym p hocyst (27%), w ound
w ere w ithin the area of d issection of the sentinel lym p h breakd ow n (11%), w ou nd infection (27%), hem atom a (2%),
nod e in 40.6% of cases. The axillary reverse m apping nod es d eep venou s throm bosis (2%), and p u lm onary em bolism
w ere the same as the sentinel nod es in 2.8% of cases. All (2%). A significant association w as m ad e betw een early
axillary reverse m ap ping nod es excised w ere negative for p ostop erative com p lications and late lym p hed em a. N o sig-
metastases. The incid ence of lym phed em a in this stu d y nificant association w as found betw een overall com plica-
w as 5.4% overall; there w ere no cases of lym p hed em a in tion rate and p ostop erative rad iation therap y (20).
patients w ho had preservation of the axillary reverse m ap - In contrast, Gou ld et al. (21) rep orted a retrospective
ping nod es (18). stu d y of 112 ingu inal lym p had enectom ies in 67 patients
w ith vu lvar carcinom a in w hich they fou nd that early com -
p lications ( 30 d ays after su rgery) d id not pred ict late
■ INGUINAL com p lications. Postop erative rad iation therap y d em on-
Inguinal lymphadenectomy (also called groin dissection) is strated a trend , thou gh not statistically significant, tow ard
performed for regional control of melanoma, vulvar carci- late lym p hed ema. Early com p lications inclu d ed cellu litis
noma, and penile carcinoma. Anatomically, the superficial (35%), w ou nd breakd ow n (19%), lym p hed em a (5%), and
inguinal lymph node dissection specimen includes the soft lym p hocyst (13%). Late com p lications inclu d ed cellu litis
tissue deep to the subcutaneous fascia extending several cen- (22%), w ou nd breakd ow n (3%), lym p hed em a (30%), and
timeters above the inguinal ligament superiorly, medially to lym p hocyst (5%) (21).
the mid d le of the ad d uctor longus muscle, inferiorly to the Rou zier et al. (22) rep orted a retrosp ective stu d y of 194
apex of the femoral triangle, and laterally to the middle of p atients w ho u nd erw ent ingu inal lym p had enectom y for
the sartorius muscle; the d eep margin is the fascia overlying vu lvar carcinom a. Logistic regression analysis found sig-
the quadriceps and sartorius muscles. A femoral dissection nificant associations betw een lym p hed em a and rad iation
includes opening the deep fascia, identifying the femoral vein, therap y, techniqu e of lym p had enectom y, and sartoriu s
and removing the deep nodes medial to it. A deep inguinal m u scle transp osition; betw een cellu litis and obesity; and
dissection is performed for extensive nodal involvement of a betw een w ou nd breakd ow n and p atient age 70 years and
superficial d issection, palpable inguinal lymphad enopathy, techniqu e of lym p had enectom y (22).
rad iologically positive pelvic nod es, or biopsy-proven d eep The techniqu e of sap henou s vein p reservation in m od -
inguinal nodal metastases. The boundaries of a deep dissec- ified ingu inal lym p had enectom y has been associated
tion are from the inguinal ligament inferiorly to the common w ith a low er incid ence of lym p hed em a, the m ost d ebili-
iliac vessels superiorly with the peritoneum reflected medi- tating com p lication of lym p had enectom y. Sap henou s
ally and superiorly. Dissection may be carried out up to the vein sp aring is p ossible in p atients w ith m inim al nod al
bifurcation of the aorta and vena cava. m etastatic d isease (e.g., m icroscop ic sentinel lym p h nod e
Com plications w ith ingu inal lym phad enectom y are m etastasis in a grossly negative nod al basin). Sap henou s
significantly m ore frequ ent than other regional lym - vein sp aring is not ad vised in p atients w ith grossly p ositive
phad enectomy p roced u res. Comp lications from ingu inal nod es, w hich tend to clu ster arou nd the sap henou s bu lb.
A retrospective review of 139 inguinal d issections in 83 H yp ocalcem ia can be avoid ed by id entification of

patients by Zhang et al. (23) compared the incid ence of lym - p arathyroid s, p rotection of their blood su p p ly, and au to-
phed ema betw een trad itional ingu inal d issection and transp lantation of d evascu larized p arathyroid s to the ster-
saphenous vein–sparing d issection. The incid ence of lym- nocleid om astoid m u scle. Transp lantation of all fou r
phed ema in the first 6 months after su rgery w as red uced p arathyroid s w as rou tinely su ccessfu l in 50 consecutive
from 70% to 32%. The evaluation at 6 months to 2 years after p atients u nd ergoing thyroid ectom y and central neck d is-
surgery show ed that the incid ence of lymphed ema red uced section for m u ltip le end ocrine neop lasia typ e 2A. In this
from 39% to 11% w ith saphenous vein preservation. The fol- techniqu e, carefu l attention m u st be p aid to p rop er id entifi-
low -up at 2 years after su rgery show ed the incid ence to be cation of p arathyroid tissu e, m incing p arathyroid tissu e
red uced from 32% in trad itional d issections to 2% in saphe- into sm all 1-mm 1-m m fragm ents, and transp lantation of
nous vein–sparing d issections. The likelihood of no com pli- fragm ents into m u ltip le intram u scu lar p ockets (26).
cations w as significantly higher in the group of patients In the left sup raclavicular region, thoracic d uct inju ry
w ith the saphenous vein preserved . Wound breakd ow n and complications can be minim ized by id entification of the tho-
cellulitis w ere significantly less common in the group of racic d uct entering the confluence of veins in the inferior
patients w ith the saphenous vein preserved . There w as no aspect of the lateral, sup raclavicu lar neck d issection. Liga-
significant d ifference in the rate of d isease recurrence tion of the d uct may be necessary if it is injured . Mass liga-
betw een the trad itional versus the sap henou s vein–sparing tion of this structure is ad vised , incorporating surround ing
d issection in this retrospective and noncontrolled stud y fat, fascia, or muscle, becau se the d u ct itself is a very thin-
(23). Saphenous vein preservation w as also associated w ith w alled structure. Careful d issection w ith attention to id enti-
significantly less lymphed ema, w ound breakd ow n, and cel- fying all structures prior to cauterization, ligation, or
lu litis by chi-squ are analysis in the stud y by Rou zier et al. transection can help to prevent inju ry to the phrenic, spinal
(22), but the logistic regression mod el analysis d id not find accessory, or hypoglossal nerves d uring d issection.
statistical significance in vein sparing ind epend ently affect- Cheah et al. (27) rep orted a review of 115 neck d issec-
ing any of those com plications. tions p erform ed on 74 p atients w ith thyroid cancer (64%
SLN B has been show n to highly significantly red u ce the p ap illary, 32% m ed u llary, and 4% follicu lar). Postopera-
rate of com p lications associated w ith ingu inal lym - tively, 23% had hyp ocalcem ia. One p atient had a neck
phad enectomy. The Su nbelt Melanom a Trial d em onstrated hematom a that requ ired a su rgical p roced u re. There w ere
a com p lication rate of 8% am ong 657 patients u nd ergoing no nerve p alsies and no inju ries to the thoracic d u ct, tra-
inguinal SLN B and a rate of 1.5% for lym phed em a com - chea, or esop hagu s. Significant factors increasing the risk of
pared w ith a previously noted total com plication rate of hyp ocalcem ia w ere concu rrent neck d issection and thy-
51% for complete inguinal dissection and an incidence of 32% roid ectom y (60% vs. 17% for d issection alone). Of those
for lym p hed em a (12). Given the high incid ence of com p li- p atients u nd ergoing concu rrent neck d issection and thy-
cations w ith ingu inal lym phad enectom y, SLN B has great roid ectom y, hyp ocalcem ia w as m ost often fou nd after cen-
potential to d ecrease the nu m ber of com plications by d is- tral d issection (75%), follow ed by central d issection and
tingu ishing those w ho w ou ld m ost benefit from a com p lete m od ified rad ical d issection com bined (67%), and then
inguinal d issection. m od ified rad ical d issection (46%) (27).
Magrin and Kow alski (28) rep orted a retrospective
stu d y of a 30-year exp erience w ith 193 consecu tive bilateral
■ HEAD AND NECK neck d issections. The p rimary tu m or locations inclu d ed
N eck d issection is perform ed for regional control in larynx (38%), tongu e (35%), hyp op harynx (12%), lips
patients w ith m alignancies of the head and neck. It (4.7%), and low er gingival area (4.1%). In the p ast 10 years
includ es central com partm ent d issection, rad ical and m od - of the stu d y, the neck d issections w ere m od ified to sp are
ified rad ical neck d issections, and parotid ectomy as ind i- the sp inal accessory nerves and both internal ju gu lar
cated . The bread th of anatom y w ithin the head and neck veins. The sp inal accessory nerve w as sp ared in 40% of
contribu tes to the m any possible com plications of lym ph cases, and the internal ju gu lar vein w as sp ared bilaterally
nod e d issection in the head and neck. in 6% of cases w ith 90% having u nilateral ligation. Com -
Com p lication s associated w ith central com p artm ent p lications occu rred in 61% of the cases. The com p lications
neck d issection in clu d e recu rren t laryn geal nerve in ju ry. and frequ ency w ere as follow s: fistu lae (30%), local w ou nd
Th is can be m in im ized by id en tification of the recu rrent infection (26%), w ou nd d ehiscence (21%), flap necrosis
laryn geal nerve throu ghou t its cou rse in the neck and (20%), chyle fistu la (2.5%), p u lm onary infection (5%), ru p -
not u sin g cau tery in the vicin ity of the nerve (24). N erve tu re of vessels (4%), hem atom a/ serom a (3%), and p ostop -
m onitorin g by variou s tech niqu es has been em p loyed to erative m ortality (2%). H istological exam ination fou nd
assist in p reventin g inju ry to the recu rren t laryn geal that 35% of p atients had no lym p h nod e involvem ent, and
nerve. N erve m on itoring h as been sh ow n to be a safe 11% had only one lym p h nod e m etastasis. There w as no
and effective techn iqu e; h ow ever, it h as not been sh ow n significant su rvival benefit for elective or therap eu tic rad i-
to be su p erior to d irect visu alization of th e recu rren t cal neck d issection w hen com p ared w ith m od ified rad ical
laryn geal n erve (25). neck d issection (28).
Mod ified rad ical neck d issection is often p erform ed in total parenteral nu trition (TPN ) and low fat d iet m ay avoid
patients w ith m elanom a of the head and neck. In the Su n- the need for a second su rgery. Fu rther conservative treat-
belt Melanom a Trial, Wrightson et al. (12) reported a p ost- m ent op tions inclu d e somatostatin (32). More invasive
op erative com p lication incid ence of 10% in 50 neck op tions inclu d e thoracic d u ct em bolization (33) and su pra-
d issection p atients w ith m elanoma. Serp ell et al. (13) also d iap hragm atic ligation of the thoracic d u ct (34).
rep orted a p ostoperative com plication incid ence of 10% in Another rare com plication of neck d issection is verte-
ten neck d issection patients w ith melanom a. bral artery inju ry. A case of bilateral cortical blind ness w as
Thou gh less m orbid than rad ical neck d issection, mod i- rep orted in a patient after right rad ical neck d issection.
fied rad ical neck d issection still can present significant Worku p revealed a hyp op lastic left vertebral artery that
fu nctional com p lications. Should er d ysfu nction, frequ ently p ossibly embolized a throm bu s that d evelop ed d u ring the
a com p lication of rad ical neck d issection, is associated w ith rotation of the neck d u ring the right neck d issection (35).
m od ified rad ical lym p h nod e d issection as w ell. In a cross- SLN B using blue d ye or rad iolabeled marker has d emon-
sectional stu d y from the University of Michigan, Chep eha strated potential for minimizing the number of negative
et al. (29) evalu ated 64 patients using Constant’s Shou ld er neck d issections and red ucing complications associated
Scale to assess should er fu nction postoperatively. Tw o w ith neck d issection. The Sunbelt Melanoma Trial reported a
grou p s w ere form ed : 32 p atients w ho u nd erw ent m od ified complication incid ence of 2.4% in a total of 370 patients,
rad ical neck d issection and 32 patients w ho u nd erw ent w hich was significantly less than the 10% complication inci-
selective d issection. The d ifference betw een the tw o p roce- d ence among patients und ergoing neck d issection for
d u res is in selectively sp aring the level V lym p h nod es, melanoma of the head and neck. This same stud y also found
w hich m ay help p revent scarring and d evascu larization of that SLN B for melanoma of the head and neck is more likely
the accessory nerve and associated cervical nerve rootlets to identify sentinel nod es in nontraditional locations and has
that can occu r w ith d issection in the posterior triangle. The a higher incidence of false negatives than sentinel node
stu d y fou nd that selective d issection p atients had a highly biopsy for melanoma of the trunk or extremities (12).
significantly better shou ld er function score. The p atient’s The cu taneou s lym p hatic d rainage of the head and neck
w eight, w hich likely correlates to better health in this p op - is highly variable and com p lex. Willis and Rid ge d em on-
u lation, w as also significantly associated w ith few er com - strated in 25 p atients w ith serial lym p hoscintigraphy stu d -
plications of shou ld er fu nction. Rad iation therap y w as ies p erform ed w ith p reop erative consu ltation and again on
fou nd to be a critical factor, thou gh not ind ep end ently sta- the d ay of surgery that lym phatic d rainage patterns m ay
tistically significant (29). vary w ithin an ind ivid u al p atient. In 8% of cases the sen-
A rare com plication associated w ith neck d issection is tinel lym ph nod e location w as d ifferent from classically
fractu re of the clavicle postoperatively. The frequ ency has p red icted p atterns. In 16% of cases there w ere d ifferent
been rep orted as approximately 0.5%. It occu rs m ost often lym p h nod e basins id entified by the tw o stud ies, w hich
as a late com p lication in association w ith sp inal accessory requ ired a m od ification of the incision to biopsy both nod al
nerve inju ry. This results in w asting of the trapeziu s, shou l- basins. In half of those cases of d iscord ance, m etastases
d er d rop , and increased torsional forces on the sternoclav- w ere fou nd in sentinel nod es from basins not id entified on
icu lar joint and clavicle, resu lting in clavicular fractu re (30). d ay of su rgery lym p hoscintigrap hy stu d ies bu t exam ined
An infrequ ent but life-threatening comp lication of neck because they w ere seen on p reoperative consultation lym -
d issection is p ostop erative ru p tu re of the internal ju gu lar p hoscintigrap hy (36).
vein. Cleland -Zam ud io et al. (31) evalu ated a series of six
cases follow ing m od ified rad ical and selective neck d issec-
tions for prim ary squam ous cell cancer of the head and
■ ABDOMINAL AND PELVIC
neck. Factors associated w ith vein ru pture inclu d ed cir- Extensive abd om inal and pelvic lym phad enectom ies m ay
cu mferential d issection of the internal ju gu lar vein low in be p erform ed for gastric and end ometrial cancers. Although
the neck and fistu la in the region of the hypopharynx low not as morbid as those involving the axilla and groin, these
in the neck. All p atients had a tobacco history and five of lymphad enectomies may result in lymphocyst formation
the six had a p oor nu tritional statu s. At em ergent re-exp lo- and persistent d rain requ irements. Franchi et al. (35)
ration, each of the involved internal jugu lar veins w as reported a stu d y that evalu ated the risk factors for postop-
fou nd to be thin-w alled and necrotic. They w ere treated by erative com p lications of p elvic lym p had enectom y. In this
ligation (31). p rosp ective stu d y, 133 p atients u nd erw ent pelvic lym -
A rare com p lication of neck d issection is chylothorax, p had enectom y w ith a com p lication rate of 34%. The m ost
w hich can be bilateral in association w ith bilateral neck d iscom m on com p lications w ere lym p hocysts and cystitis.
section. This can result from a m issed thoracic d u ct inju ry Mu ltip le logistic regression analyses fou nd that the only
or after the thoracic d uct is ligated , likely second ary to high factor significantly associated w ith p ostop erative com p li-
intralu m inal p ressu res that resu lt in extravasation of chyle cations w as rem oval of m ore than 14 lym p h nod es (37).
throu gh the w alls of the d uct. The chyle leak m ay not p res- Op erative techniqu es, su ch as om entop exy, have been u ti-
ent throu gh the neck d rain and m ay requ ire thoracentesis lized w ith som e su ccess to red u ce the comp lications of
to d etect. Conservative treatm ent w ith chest tu be d rainage, lym p horrhea and lymp hocyst form ation (38).
Persistent leaking from severed lymphatics due to cau- of postoperative leakage. The 5-year survival w as greater for
terization is one contributor to lymphadenectomy complica- the extend ed lymphad enectomy group (66% vs. 48%), but
tions. A prospective, randomized study by Tsimoyiannis this w as not statistically significantly d ifferent (42).
et al. (37) evaluated the effectiveness of ultrasonic shears in Fu jita et al. (38) rep orted a retrosp ective stu d y of 302
extend ed lymphad enectomy for gastric cancer. These shears p atients w ho u nd erw ent cu rative transthoracic esophagec-
utilize ultrasonic w aves to d enature proteins forming a tomy w ith stand ard (40 p atients), extend ed (21 patients),
coagulum that seals vessel w alls and thereby w ould hypo- total (65 p atients), or three-field (176 p atients) lym -
thetically prevent lymphorrhea. Forty patients w ere stud ied. p had enectom y. The incid ence of recu rrent laryngeal nerve
Tw enty underw ent resection and lymphadenectomy using p alsies w as d irectly related to the extent of lym p had enec-
the traditional monopolar cautery, hemoclips, and ligation. tomy w ith an incid ence of 57% overall, 69% three-field ,
The other 20 underw ent resection and lymphad enectomy 55% total, 20% extend ed , and 23% stand ard lym p had enec-
using ultrasonically activated coagulating shears, reserving tomy (40).
hemoclips and ligation only for vessels 3 mm in diameter.
The group utilizing the ultrasonic shears had significantly
less intraoperative blood loss and less abd ominal d rainage
■ CONCLUSION
postoperatively. They w ere also able to have abd ominal Lym p had enectom y can p rovid e an effective m eans of
drains removed significantly earlier and had a significantly regional control of cancer, althou gh it bears the cost of
shorter hospital stay. While there w as no significant differ- p otentially m orbid com p lications. Ap p reciating these com -
ence in the number of patients w ho w ere transfused , the p lications is im p ortant for su rgeons to avoid experiencing
patients treated w ith ultrasonic shears required significantly them and to provid e their patients w ith the m ost effective
fewer units of blood (39). and least m orbid treatm ents. SLN B p rovid es a tool for sur-
geons to better d eterm ine w hich p atients w ill benefit from
m ore extensive lym p had enectom y and w hich ones can be
■ THORACIC spared of its com p lications w hile not com prom ising their
The high frequency of lymphatic metastases from esophageal cancer treatm ent.
cancer has made mediastinal lymphadenectomy an impor-
tant part of the regional treatment of this disease. Complica- ■ REFERENCES
tions associated with this include chyle leaks, nerve injury,
1. Krag D, Weaver D, Ashikaga T, et al. The sentinel nod e in breast can-
and pulmonary infections. The stand ard treatment for chyle cer—a m ulticenter valid ation stu d y. N Engl J Med 1998;339:941–946.
leaks includes drainage, total parenteral nutrition, a low-fat 2. Morton DL, Wen DR, Won g JH , et al. Techn ical d etails of in traop era-
diet with medium chain fatty acid supplements, and tive lym p hatic m ap p ing for early stage m elanom a. Arch Surg 1992;127:
392–399.
octreotide to reduce lymphatic production. Supradiaphrag- 3. McMasters KM, N oyes RD, Reintgen DS, et al. Lessons learned from
matic ligation of the thoracic duct may be necessary (34). the Su nbelt Melanom a Trial. J Surg Oncol 2004;86:212–223.
The high incid ence of nod al m etastases to the region of 4. Bu rak WE, H ollenbeck ST, Zervos EE, et al. Sentinel lym p h nod e
biop sy resu lts in less p ostop erative m orbid ity com p ared w ith axillary
the recu rrent laryngeal nerves increases the risk of nerve lym ph nod e d issection for breast cancer. Am J Surg 2002;183:23–27.
in ju ry d u ring th oracic lym p h ad enectom ies (40). Griffin 5. Schijven MP, Vingerhoets AJ, Ru tten H J, et al. Com p arison of m orbid ity
et al. (39) rep orted a prosp ective series of 228 patients w ho betw een axillary lym ph nod e d issection and sentinel nod e biop sy. Eur J
Surg Oncol 2003;29:341–350.
und erw ent su btotal esophagectom y and tw o-field lym - 6. Carcoforo P, Soliani G, Maestroni U, et al. Octreotid e in the treatm ent of
phad enectomy. The recurrent laryngeal nerve w as not d is- lym p horrhea after axillary nod e d issection: a prospective rand om ized
sected w ith the rem oval of nod es in the aortop u lm onary controlled trial. J Am Coll Surg 2003;196:365–369.
7. Schrenk P, Rieger R, Sham iyeh A, et al. Morbid ity follow ing sentinel
w ind ow in an effort to red u ce nerve inju ry. Cervical lym - lym p h nod e biopsy versu s axillary lym ph nod e d issection for patients
phad enectomy w as not perform ed . The most com m on w ith breast carcinom a. Cancer 2000;88:608–614.
postoperative com p lication w as pulm onary infection at 8. Talbot ML, Magarey CJ. Red u ced u se of d rains follow ing axillary lym -
phad enectom y for breast cancer. ANZ J Surg 2002;72:488–490.
15%. The incid ence of chyle leaks w as 0.8%. The incid ence 9. Moore M, Bu rak WE Jr, N elson E, et al. Fibrin sealant red u ces the d u ra-
of laryngeal nerve p alsy w as 0.4% (41). tion and am ount of fluid d rainage after axillary d issection: a rand om -
N ishihira et al. (40) reported a prospective rand omized ized p rosp ective clinical trial. J Am Coll Surg 2001;192:591–599.
10. Brennan MJ, DePom p olo RW, Gard en FH . Focu sed review : p ostm as-
trial com paring 32 patients und ergoing extend ed lym- tectom y lym p hed em a. Arch Phys Med Rehabil 1996;77:S74–S80.
phadenectomy, w hich included superior mediastinal and 11. Velanovich V, Szym anski W. Qu ality of life of breast cancer p atients
cervical d issection, versus 30 patients und ergoing conven- w ith lym phed em a. Am J Surg 1999;177:184–187.
12. Wrightson WR, Wong SL, Ed w ard s MJ, et al. Com p lications associated
tional lymphad enectomy for esophageal cancer. There w as w ith sentinel lym p h nod e biop sy for m elanom a. Ann Surg Oncol 2003;
no significant difference in pulmonary complications. 10:676–680.
Recurrent laryngeal nerve injury, how ever, had an incidence 13. Serp ell JW, Carne PW, Bailey M. Rad ical lym p h nod e d issection for
m elanom a. ANZ J Surg 2003;73:294–299.
of 56% among extend ed lymphad enectomy patients w hen 14. Su am i H , Pan WR, Mann GB, et al. The lym p hatic anatom y of the
compared w ith 30% of conventional lym phad enectomy breast and its im p lications for sentinel lym p h nod e biop sy: a hu m an
patients. Extended lymphadenectomy was also associated cad aver stu d y. Ann Surg Oncol 2008;15:863–871.
15. Mu llan MH , Deacock SJ, Qu iney N F, et al. Anap hylaxis to p atent blu e
w ith a higher incid ence of phrenic nerve palsy and tra- d ye d u ring sentinel lym ph nod e biop sy for breast cancer. Eur J Surg
cheostom y. Conventional d issection had a higher incid ence Oncol 2001;27:218–219.
16. Woltsche-Kahr I, Kom ericki P, Kranke B, et al. Anap hylactic shock fol- 30. H alfp enny W, Good ger N . Early fractu re of clavicle follow ing neck d is-
low ing p eritu m oral injection of patent blue in sentinel lym ph nod e section. J Laryngol Otol 2000;114:714–715.
biopsy p roced u re. Eur J Surg Oncol 2000;26:313–314. 31. Cleland -Zam u d io SS, Wax MK, Sm ith JD, et al. Ru p tu red internal ju gu -
17. Strad ling B, Aranha G, Gabram S. Ad verse skin lesions after m ethylene lar vein: a postoperative com plication of m od ified / selected neck d is-
blue injections for sentinel lymp h nod e localization. Am J Surg 2002;184: section. Head Neck 2003;25:357–360.
350–352. 32. Al-Sebeih K, Sad eghi N , Al-Dhahri S. Bilateral chylothorax follow ing
18. Boneti C, Korourian S, Diaz Z, et al. Scientific Impact Aw ard : axillary neck d issection: a new m ethod of treatm ent. Ann Otol Rhinol Laryngol
reverse m ap ping (ARM) to id entify and protect lym phatics d raining the 2001;110:381–384.
arm d uring axillary lymphad enectom y. Am J Surg 2009;198:482–487. 33. Patel N , Lew and ow ski RJ, Bove M, et al. Thoracic d u ct em bolization: a
19. Bevan-Thom as R, Slaton JW, Pettaw ay CA. Contem p orary m orbid ity new treatm ent for m assive leak after neck d issection. Laryngoscope
from lym phad enectom y for p enile squ am ou s cell carcinom a: the M.D. 2008;118:680–683.
And erson Cancer Center Exp erience. J Urol 2002;167:1638–1642. 34. Patterson GA, Tod d TR, Delaru e N C, et al. Su p rad iap hragm atic liga-
20. Gaarenstroom KN , Kenter GG, Trim bos JB, et al. Postop erative com p li- tion of the thoracic d uct in intractable chylou s fistu la. Ann Thorac Surg
cations after vu lvectom y and ingu inofem oral lym p had enectom y using 1981;32:44–49.
sep arate groin incisions. Int J Gynecol Cancer 2003;13:522–527. 35. Raj P, Moore PL, H end erson J, et al. Bilateral cortical blind ness: an
21. Gou ld N , Kam elle S, Tillm anns T, et al. Pred ictors of com p lications unu su al com p lication follow ing u nilateral neck d issection. J Laryngol
after ingu inal lym p had enectom y. Gynecol Oncol 2001;82:329–332. Otol 2002;116:227–229.
22. Rou zier R, Feyereisen E, Constancis E, et al. Frozen section exam ina- 34. Willis AI, Rid ge JA. Discord ant lym p hatic d rainage p atterns revealed
tion of the end ocervical m argin of cervical conization specim ens. by serial lym p hoscintigrap hy in cu taneou s head and neck m alignan-
Gynecol Oncol 2003;90:305–309. cies. Head Neck 2007;29:979–985.
23. Zhang SH , Sood AK, Sorosky JI, et al. Preservation of the sap henou s 35. Franchi M, Ghezzi F, Riva C, et al. Postop erative com p lications after
vein d u ring ingu inal lym p had enectom y d ecreases m orbid ity in pelvic lym p had enectom y for the surgical staging of end om etrial can-
patients w ith carcinom a of the vu lva. Cancer 2000;89:1520–1525. cer. J Surg Oncol 2001;78:232–237.
24. Moley JF, Lairm ore TC, Doherty GM, et al. Preservation of the recu r- 36. Fu jiw ara K, Kigaw a J, H asegaw a K, et al. Effect of sim p le om entop lasty
rent laryngeal nerves in thyroid and p arathyroid reop erations. Surgery and om entop exy in the prevention of com p lications after pelvic lym -
1999;126:673–677. phad enectom y. Int J Gynecol Cancer 2003;13:61–66.
25. Dralle H , Seku lla C, H aerting J, et al. Risk factors of p aralysis and fu nc- 37. Tsim oyiannis EC, Jabarin M, Tsim oyiannis JC, et al. Ultrasonically acti-
tional outcom e after recurrent laryngeal nerve m onitoring in thyroid vated shears in extend ed lym p had enectom y for gastric cancer. World J
su rgery. Surgery 2004;136:1310–1322. Surg 2002;26:158–161.
26. Skinner MA, Moley JF, Dilley WG, et al. Prop hylactic thyroid ectom y 38. Fu jita H , Su eyoshi S, Tanaka T, et al. Op tim al lym p had enectom y for
in m u ltip le end ocrin e neop lasia typ e 2A. N Engl J Med 2005;353: squ am ous cell carcinom a in the thoracic esophagus: com paring the
1105–1113. short- and long-term outcom e am ong the four types of lym phad enec-
27. Cheah WK, Arici C, Itu arte PH , et al. Com p lications of neck d issection tom y. World J Surg 2003;27:571–579.
for thyroid cancer. World J Surg 2002;26:1013–1016. 39. Griffin SM, Shaw IH , Dresner SM. Early com p lications after Ivor Lew is
28. Magrin J, Kow alski L. Bilateral rad ical neck d issection: resu lts in 193 subtotal esophagectom y w ith tw o-field lym phad enectom y: risk factors
cases. J Surg Oncol 2000;75:232–240. and m anagem ent. J Am Coll Surg 2002;194:285–297.
29. Chepeha DB, Taylor RJ, Chep eha JC, et al. Fu nctional assessm ent u sing 40. N ishihira T, H irayam a K, Mori S. A p rosp ective rand om ized trial of
Constant’s Shou ld er Scale after m od ified rad ical and selective neck d is- extend ed cervical and su p erior m ed iastinal lym p had enectom y for car-
section. Head Neck 2002;24:432–436. cinom a of the thoracic esop hagu s. Am J Surg 1998;175:47–51.
PART
VII
Complications of
Transplantation
CHAPTER
47
Complications of
Renal Transplantation
Randall Sung and Robert Merion
■ OVERVIEW OF RENAL TRANSPLANTATION tw o categories: those related to organ p rocu rem ent and
those related to the recip ient op eration.
Transplantation of the kidney is usually a straightforward
operative procedure. Improved immunosuppressive regi-
mens and antirejection therapies have resulted in patient sur- ■ Donor-related complications
vival rates in excess of 97% and graft survival rates in excess Deceased Donors
of 93% 1 year following transplantation. As most experienced
Techniqu es for the p rocu rem ent of m u ltip le organs from
transplantation surgeons are aw are, however, the road to this
d eceased d onors have been stand ard ized for m any years
excellent overall result can have many twists and turns. For
(3). With the u se of in situ cold p erfu sion, the kid neys are
example, as many as 8% of renal transplant recipients experi-
p rotected from w arm ischem ic inju ry from the m om ent of
ence a complication related to the urinary system (1,2). If one
d onor aortic cross-clam p ing, avoid ing the frantic, hurried
also considers nonurologic problems requiring operative or
removal of organs that m ay lead to technical m isad ventu re.
percutaneous intervention, such as local infection, lympho-
The use of in situ perfu sion com bined w ith en bloc rem oval
cele, or vascular compromise, as many as 20% of patients
of the kid neys for separation on the back bench lim its the
may experience a significant perioperative complication.
p ossibility of inju ries to the vascu lar stru ctu res of renal
Com plications follow ing renal transplantation m ay be
allografts. Dissection on the back bench p erm its easy id en-
related to p red isposing recipient factors, issues d eriving
tification of anom alou s vascu lar stru ctu res from w ithin the
from characteristics of the d onor kid ney or d onor kid ney
aorta so that no d issection in the renal hilu m is necessary.
procu rem ent su rgery, preservation-related inju ry, recip ient
Vascu lar inju ries to both the renal artery and vein can occu r
operative m isad ventu re, or com plications of the obligate
in the context of p ancreas and liver recovery, and careful
im m u nosu p p ressed state. Effective im m u nosu p p ression
attention to these stru ctu res w hen d ivid ing the su perior
red u ces host resistance to infection and d elays w ou nd heal-
m esenteric artery and inferior vena cava is necessary to
ing. Transp lant recipients them selves are often d ebilitated
avoid inad vertent inju ry.
as the resu lt of p oor nu trition or und erlying d isease, su ch
as d iabetes m ellitu s or card iovascular d isease. The trans- Volunteer Living Donors
planted kid ney itself m ay be d am aged at the tim e of organ
procu rem ent and m ay harbor bacterial or viral pathogens. Inju ry to a kid ney procu red from a volu nteer living d onor
These factors notw ithstand ing, renal transplantation is safe is u ncom m on. Preop erative id entification of the renal arte-
and effective. Years of previous clinical experience and rial and venou s stru ctu res, u su ally via com pu ted tom o-
new er d iagnostic techniques have allow ed for earlier d iag- grap hic (CT) scanning, allow s the su rgeon to id entify
nosis and treatm ent of com plications, w ith su bsequ ently p otential anom alies, su ch as m u ltip le renal arteries or early
red u ced m orbid ity and m ortality. renal arterial branching, as w ell as occu lt vascu lar pathol-
ogy (e.g., aneu rysm, fibrom u scu lar d ysp lasia, and renal
artery stenosis). This im aging m od ality has largely
■ VASCULAR COMPLICATIONS rep laced conventional selective renal arteriography (4). Up
to 40% of p rosp ective living d onors m ay have anatom ical
■ Early vascular complications
arrangem ents other than a single artery and vein (5).
Most acu te vascu lar com p lications follow ing renal trans- Ad d itional factors in the living d onor kid ney, such as
plantation are technical in origin and are potentially p re- shorter lengths of renal artery and vein, the absence of Car-
ventable. Early vascular com plications can be d ivid ed into rel p atches of aorta and vena cava, and the need for d irect
cannu lation of the renal artery for cold p erfu sion, have the
Randall Sung: University of Michigan, Ann Arbor, MI p otential to make the recip ient operation m ore d ifficult.
48109-5331 Desp ite these theoretical issu es, the incid ence of vascu lar
Robert Merion: University of Michigan; Arbor Research com p rom ise d oes not ap p ear to be increased in recip ients
Collaborative for H ealth, Ann Arbor, MI 48109-5331 of living d onor kid neys.
613
614 Part VII • Complications of Transplantation
Lap aroscop ic d onor nephrectom y, introd u ced in the is p ossible, w ith throm bectom y and reconstru ction of the
m id -1990s (6–8), is now used for 90% of living d onor arterial anastom osis or via interventional rad iology tech-
renal p rocu rement p roced ures. While a learning cu rve w as niqu es (11–13). The graft shou ld be assessed for viability
initially d escribed , as w as a slight increase in d elayed graft if a thrombectom y is to be consid ered . Unfortu nately,
fu nction (DGF), this has largely been overcom e w ith exp e- rem oval of an infarcted graft is the ou tcom e in m ost cases.
rience. As w ith op en nephrectom y, attention to renal p erfu - If the p roblem is w ith the recip ient iliac artery, significant
sion throu gh ad equ ate intravenou s flu id ad m inistration iliac arterial reconstruction m ay be necessary.
and avoid ance of excessive m anipu lation, accom p anied by
the u se of m annitol or a loop d iu retic, is recom m end ed to Polar Artery Occlusion
m inim ize this p roblem . Disad vantages w ith red u ced renal Carefu l attention to the d etails of organ procu rem ent
vessel and u reter length have largely been elim inated w ith shou ld p revent m issed or inad vertently ligated polar ves-
experience and ad vances in the laparoscop ic stap ler tech- sels. These circu m stances are usually evid ent at the tim e of
nology, bu t at any rate d o not present an und u e challenge revascu larization, w ith sharp d em arcation of the involved
for the recip ient p roced u re. segment. If the segment is sufficiently large, vascu lar recon-
stru ction should be carried out if possible to m axim ize
■ Recipient-related complications viable nep hron m ass and to prevent p ossible sequ elae of
segm ental p arenchym al infarction, w hich m ay includ e
Arterial Thrombosis infection, urine leak, ureteral infarction, and post-transplant
Arterial throm bosis has a reported incid ence of 0.5% to 2% hyp ertension. If rep air is not p ossible or the p arenchym a
(9,10). In rare instances, acute occlusion of the allograft involved com p rises 10% of the renal volu m e, treatm ent
renal artery m ay be noted at the tim e of transp lantation, m ay be exp ectant. In m ost of these cases, no p roblem s
w hen p otentially rem ed iable lesions, such as intim al tears, d evelop .
native or d onor renal artery d issection, im proper constru c-
tion of the arterial anastom osis, or acute angulation of the Hemorrhage
vessel, shou ld be id entified and corrected . Mu ltiple renal Second ary hem orrhage from anastom otic leak or m ycotic
arteries (p articu larly if they are not on a com m on aortic aneu rysm is a relatively rare com p lication of renal trans-
patch), severe atherosclerotic vascular d isease in the recip i- p lantation, occu rring w ith an incid ence of 0.3% to 3.5%
ent, and recip ient throm bop hilia m ay all contribu te to an (14–16). Althou gh arterial throm bosis and hem orrhage are
increased risk of arterial com p rom ise. It should be noted equ ally u ncom m on, the latter is associated w ith an
that not all vascu lar throm bosis is technical. Arterial extrem ely high m ortality. H em orrhage that occu rs w ithin
throm bosis m ay rep resent the end p oint of accelerated or the first 12 to 24 hou rs of op eration is m ost likely d u e to
hyp eracu te rejection, or severe ischem ic reperfu sion inju ry. su rgical error or incom p lete hem ostasis, and retu rn to the
An u nusu al cau se of intraoperative p roblem s is com pres- op erating room is ind icated . Patients w ith throm bop hilia
sion of the p roxim al iliac artery or vein by a retractor. are at risk for vascu lar throm bosis follow ing kid ney trans-
H yp operfu sion or venou s engorgem ent of the transplanted p lantation, and p eriop erative anticoagu lation is requ ired
kid ney m ay resu lt, lead ing to an ill-ad vised exploration of in these ind ivid u als. Dep end ing on the severity of the p ro-
the anastom otic sites u ntil the offend ing d evice is d iscov- throm botic state and the intensity of anticoagu lation, sig-
ered and rem oved . nificant p ostop erative hem orrhage m ay occu r in as m any
Renal dysfunction in the immediate postoperative phase as 65% of these p atients (14,17). Und er these circu m -
suggests the possibility of arterial thrombosis. Prompt d iag- stances, op erative intervention is less likely to control the
nosis is imperative because the transplanted kidney has no bleed ing, and red u ction or tem p orary cessation of antico-
collateral circulation to support the renal parenchyma. agu lation m ay be necessary to stop the bleed ing. Since
Although absence or abrupt cessation of urine output is per- p ostop erative hem orrhage is so com m on in these p atients,
haps the most suggestive sign of arterial thrombosis, the dif- carefu l attention m u st be p aid to other com orbid ities, p ar-
ferential d iagnosis includ es other far more common causes. ticu larly card iovascu lar d isease, w hen selecting patients
The initial ap p roach to the p atient w ith anu ria or olig- w ith throm bop hilia for transplantation.
uria follow ing transp lantation, once obstruction of the u ri- Later hem orrhage is often related to an infectiou s com -
nary catheter is ru led out by irrigation, is to p erform p lication. Leakage of infected u rine, m ycotic aneu rysm , or
ultrasonograp hic exam ination of the renal allograft to necrosis of renal p arenchym a second ary to a throm bosed
assess the ad equ acy of renal perfu sion. While renal arteri- p olar artery m ay be resp onsible. Attem p ted rep air of an
ograp hy m ay be help fu l in p lanning an op erative interven- infected , leaking anastom osis can only be d escribed as fool-
tion, u nd er most circu mstances, the d elay in treatm ent is hard y becau se bleed ing invariably recu rs. It is far safer to
not justified if flow in the kid ney cannot be id entified by remove the allograft. Becau se the arterial anastom osis is
ultrasou nd . u su ally p erform ed end to sid e to the external iliac artery,
Once the d iagnosis of arterial throm bosis is su sp ected , ligation of the ip silateral native vessel m ay be necessary.
im m ed iate exp loration offers the only hope for salvage. If While acu te lim b-threatening low er extrem ity ischem ia is
id entified early enou gh (w ithin hours), salvage of the graft fortu nately rare in this situ ation (18), extraanatom ic bypass
Chapter 47 • Complications of Renal Transplantation 615
to the affected extrem ity m ay be requ ired if ischem ia may also occur in the setting of late chronic rejection, w here
ensu es. Becau se the d onor m ay be the sou rce of contam ina- fibrosis may prevent contraction around the need le tract.
tion that m ay later lead to life-threatening hem orrhage, The use of antiplatelet agents such as clopidogrel or aspirin
ad m inistration of p rophylactic antibiotics to all recip ients may increase this risk, although d ata on the incid ence in
of renal allografts is recom m end ed (19). patients taking these drugs are limited and the safety of
biopsy w ithout d iscontinuation is controversial. This is an
Renal Vein Thrombosis increasingly important m anagement consid eration, as more
The overall incid ence of venou s throm bosis is abou t 0.5% and more recipients with coronary stets and cardiovascular
to 4% (20–24). Allograft renal vein throm bosis can occu r via d isease are using these agents, and the implications of stop-
a nu m ber of m echanism s. Im proper placem ent of the graft ping these agents with respect to both stent reocclusion and
in the iliac fossa m ay resu lt in kinking or tw isting of the d elay in d iagnosis of kid ney rejection are significant.
venou s anastomosis, especially if the renal vein is left too Arteriovenous fistulae have also been reported following
long. Attention to the orientation of the renal vein and the percutaneous biopsy. Most are peripheral arteriovenous fis-
choice of anastom otic site on the iliac vein are im p ortant. tulae, remain small and asymptomatic, and spontaneously
Allograft renal vein throm bosis m ay also be encountered in regress (30). Thus, management is expectant for these arteri-
association w ith severe rejection or concom itantly w ith ovenous fistulae. Central hilar fistulae are usually larger,
arterial throm bosis. In these cases, the venou s throm bosis present with a continuous high-pitched bruit, and are associ-
is a second ary occu rrence. ated w ith evidence of renal d ysfunction, hypertension,
The usual presentation is herald ed by su d d en pain at hemolytic anemia, and, occasionally, heart failure. Larger,
the transp lant site, accom p anied by sw elling and tend er- symptomatic fistulae may be treated by ligation, emboliza-
ness of the graft. H em atu ria, m arked ly d ecreased u rinary tion, or nephrectomy (30–32).
ou tp u t, and p roteinuria m ay be noted . Renal vein throm bo-
sis m ay occu r in the p resence of extensive iliofem oral
venou s throm bosis, often m onths after transplantation.
■ Transplant renal artery stenosis
Parad oxically, the presentation m ay inclu d e hem orrhage Transp lant renal artery stenosis is a w ell-characterized late
from the transp lant incision d u e to second ary venou s ru p - com p lication of renal transp lantation, u su ally presenting
ture of the graft (20). There are very few su ccessfu l ou t- w ith hyp ertension and a variable d egree of allograft d ys-
com es w hen renal vein throm bosis occu rs in the early fu nction. Since the long-term effects of u ncontrolled hyp er-
post-transp lant p eriod (20,21,23). Therefore, prevention is tension are significant for both allograft and patient, it is
of p aram ou nt im p ortance. H ow ever, as in arterial throm - im portant to d ifferentiate transplant renal artery stenosis
bosis, p rom p t recognition and im m ed iate op erative inter- from other cau ses of p ost-transp lant hyp ertension.
vention are essential for graft salvage.
Incidence and Etiology
The etiology of transp lant renal artery stenosis is m u ltifac-
■ Deep venous thrombosis torial. Inju ry to the intim a of the renal artery d uring organ
In general, throm botic com plications follow ing renal trans- p rocu rem ent, p erfu sion, or im p lantation m ay lead to anas-
plantation are rare, especially consid ering the fact that sys- tom otic or p ostanastom otic stenosis. Kinking, angu lation,
tem ic heparinization is usually not em p loyed d u ring and torsion of the artery m ay be contribu ting factors in
vascu lar clam p ing, w hich is u nu sual for vascu lar surgical som e cases. Chronic rejection or p rogressive atherosclerotic
proced u res. Uremic platelet d ysfu nction in transp lant recip- vascu lar d isease has also been noted . Becau se many renal
ients typically p revents both arterial and venous com p lica- transplant p atients are hyp ertensive at baseline and are not
tions from occu rring. N evertheless, the incid ence of stu d ied comp letely, the tru e incid ence of transp lant renal
post-transp lant Deep Vein Thrombosis (DVT) has ranged artery stenosis is u nknow n. The rep orted incid ence has
from 1% to 2%, and some form of DVT p rophylaxis, either ranged from 0.9% to as high as 23% in a series of 100
low er extrem ity com pression d evices or low -d ose hep arin, p atients stu d ied w ith rou tine p ost-transp lant arteriogra-
or both are recommend ed (24,25). H ypercoagulable states, p hy (33). Most su rgical series rep ort an incid ence of 2% to
DGF, and proteinuria all pred ispose to venous thrombosis, 5% (21,33–38).
and , as m entioned earlier, extension of an iliofemoral DVT
to the renal vein can threaten the function of the allograft. Diagnosis
Clinically im p ortant hyp ertension d u e to transp lant renal
Vascular Complications of Percutaneous Biopsy artery stenosis m ay becom e m anifest from several w eeks to
Although percutaneous allograft biopsies are generally safe, several years after transp lant, bu t m ost p resent w ithin 6 to
hemorrhage is alw ays a possible complication (26,27). The 8 m onths w ith either new onset of hyp ertension or exacer-
incid ence of bleed ing requiring transfusion has been bation of p reexisting hyp ertension. Since m ost kid ney
reported as betw een 0.1% and 1% (28,29). Rarely, transplant transplant recipients experience som e d egree of hyp erten-
nephrectomy may be required d ue to uncontrolled post- sion, the p attern of blood p ressu re control m u st be assessed
biopsy retroperitoneal hemorrhage. Postbiopsy hemorrhage carefu lly. A bru it m ay often be heard over the graft. Renal
FIGURE 47.1. A: Normal Doppler ultrasound tracing from a transplanted kidney. B: Transplant renal artery stenosis showing a tardus
waveform. C: Doppler ultrasound appearance of reversed diastolic flow associated with allograft rejection or venous obstruction.
d ysfunction may be noted but is often a late sign. There are tw o basic p atterns of stenosis in transp lant
Angiotensin- converting enzym e inhibitors m ay cau se recip ients, either an anastom otic lesion or p ostanastom otic
severe, usually reversible renal d ysfunction in the presence narrow ing. A short segm ent of stenosis su ggests technical
of transplant renal artery stenosis (39). p roblem s, su ch as inju ry from the tip of a p erfu sion can-
Screening is accomplished by Doppler ultrasonography, nu la or extrinsic com p ression by fibrou s band s, w hereas a
w hich in experienced hand s is highly accurate in d etermin- longer segm ent m ay be related to rejection, the so-called
ing the p resence or absence of transp lant renal artery im m u nologic stenosis (37).
stenosis and can d ifferentiate this entity from other cau ses
of p ost-transp lant allograft d ysfu nction (40) (Fig. 47.1). Treatment
Som e centers confirm the d iagnosis by m agnetic reso- Before the 1980s, the treatm ent of transp lant renal artery
nance angiograp hy (MRA) (41). The MRA is noninvasive stenosis consisted p rim arily of su rgical intervention. The
and u ses a non-nep hrotoxic d ye load bu t is generally transabd om inal ap p roach w as p referred becau se of the
low er resolu tion than a conventional angiogram . The relative ease of d issection of the involved blood vessels
d iagnosis of transp lant renal artery stenosis shou ld be com p ared w ith the extrap eritoneal techniqu e. Id entifica-
confirm ed by either selective bip lane angiograp hy or CT tion of the u reter is im p ortant d u ring the d issection, as it
angiograp hy to d elineate the anatom y and the location, m ay lie in close p roxim ity to the renal vascu latu re. Su rgi-
characteristics, and severity of the resp onsible lesion. Fig- cal op tions inclu d e au togenou s vein p atch angiop lasty or
u re 47.2A is an MRA and Figu re 47.2B is a conventional byp ass, end arterectom y, and excision and reanastom osis.
angiogram (d igital su btraction techniqu e) that show s a Transp lant nep hrectom y is only rarely ind icated . Am ong
tight stenosis at the renal artery anastom osis. The p atient several com bined series, the overall su ccess rate for op era-
had d evelop ed increasing hyp ertension and renal d ys- tive treatm ent w as 77% (21,33,34,38). The overall m ortality
fu nction 20 m onths after transp lant from a living related w as 3.6%, and u p to 15% of grafts w ere lost as a resu lt of
d onor. The lesion w as su ccessfu lly d ilated w ith p ercu ta- su rgical intervention.
neou s translu m inal angiop lasty at the tim e of angiogra- Percu taneou s translu m inal angiop lasty w ith or w ithou t
p hy (Fig. 47.2C). stenting has now largely replaced op erative intervention as
A B
FIGURE 47.2. A: Magnetic resonance angiogram demonstrating

a critical stenosis at the anastomosis between the transplant renal
artery and the recipient external iliac artery. B: Conventional digital
subtraction angiogram demonstrating the anastomotic stenosis
(arrow). C: The lesion following transluminal balloon angioplasty
C with resolution of the pressure gradient across the anastomosis
(22 mm Hg–8 mm Hg).
d efin itive th erap y in m ost cases. Desp ite occasion al ■ EARLY POST-TRANSPLANT
com p lication s, th e m ajority of stu d ies sh ow a rate of
RENAL DYSFUNCTION
su ccess as h igh as 92%, as ju d ged by angiograp h ic an d
hem od yn am ic im p rovem en t, red u ction in system ic Oligoanu ric renal failu re follow ing transp lantation is a
blood p ressu re, im p rovem en t in ren al fu n ction , an d com m on occu rrence; the incid ence ranges from 10% u p
low er m orbid ity an d m ortality w h en com p ared w ith to 60% in rep orted series (47–51).
op en su rgical tech n iqu es (42–46). In th e largest rep ort so
far, 88% of 55 p atients h ad a su ccessfu l angiop lasty by
■ Delayed graft function
both arteriograp h ic an d blood p ressu re criteria (43). N o
grafts w ere lost, an d th ere w as on e d eath . Graft fu n ction DGF second ary to acu te tu bu lar necrosis is by far the m ost
w as im p roved in half of th e cases, an d recu rren ces w ere com m on cau se and is consid ered not a com p lication p er se,
rare. but an only partially avoid able consequ ence of ischem ic
injury to the kid ney. DGF is m ost com m only d efined as the 4 L p rior to rep erfu sion in generally su fficient, although
need for d ialysis in the first w eek follow ing transplant; this can be m od ified as the p atient’s card iac and vol-
how ever, it shou ld be recognized that occasionally d ialysis u m e/ d ialysis statu s m ay w arrant. Mannitol is given at a
is requ ired im m ed iately follow ing transplant for severe d ose of 0.5 to 0.75 g/ kg ju st p rior to release of the vascu lar
hyp erkalemia d espite acceptable u rine ou tput and subse- clam p s, and systolic blood p ressu re is kep t at least 100 m m
qu ent graft fu nction. DGF rates vary by type of d eceased H g. Ad d itional intravenou s flu id is given p ostop eratively,
d onor: they are typically 20% or less after stand ard and u rine ou tp u t is rep laced volu m e for volu m e for the
d eceased d onor transplants. Exp and ed criteria d onors first 12 to 24 hou rs. Becau se of the synergistic nephrotoxic
(ECDs) are d efined as kid neys from d onors aged 60 years effect of calcineu rin inhibitors on ischem ically d am aged
or old er, or from d onors aged 50 to 59 years w ith at least kid neys (55), these agents are frequ ently w ithheld until
tw o of the follow ing: cerebrovascu lar accid ent as cau se of d iu resis is established and the seru m creatinine has fallen.
d eath, term inal seru m creatinine 1.5 m g/ d L, or a history Until then, p atients receive im m u nosu p p ression w ith an
of hyp ertension. DGF occu rs in approxim ately 30% of ECD antim etabolite, su ch as m ycop henolate m ofetil, corticos-
transp lants (52). Ap p roximately 9% of d eceased d onor kid - teroid s, and , if DGF is p rolonged , ad m inistration of an anti-
neys com e from d onors after card iac d eath (DCD, as lym phocyte antibod y.
opposed to d onors that are brain d ead , BDD); these kid -
neys have sim ilar graft survival to those from BDD, bu t
■ Diagnosis
have a 40% rate of DGF. Living d onor kid neys rarely exp e-
rience DGF; this is attribu table to the hem od ynam ic stabil- The approach to the p atient w ho exhibits intrinsic renal
ity of the live d onor and the extrem ely short cold ischem ia d ysfu nction im m ed iately follow ing transp lantation shou ld
tim es, w hich is a risk factor for DGF. focu s on the rap id id entification of correctable u nd erlying
cau ses to red u ce the chances of u ltim ate graft loss. The
d iagnosis of p reservation-associated acu te tu bu lar necrosis
■ Etiology or DGF is one of exclu sions.
Extrinsic Causes Urinary Drainage
Many factors m ay be resp onsible for p ost-transp lant renal
The first priority should be the assu rance of a freely d rain-
d ysfunction. These includ e vascular throm bosis, low er u ri-
ing u rinary catheter. Blood clots in the blad d er or in the
nary tract obstru ction, and hyperacute or accelerated rejec-
catheter can frequ ently be rem oved by gentle irrigation
tion. Meticu lou s attention to the surgical technique d u ring
w ith sterile saline solu tion. When d ou bt exists abou t the
organ p rocu rem ent and transp lantation p revents m ost
p atency of the u rinary catheter, it shou ld be rep laced .
cases of acute vascu lar com promise and u rinary obstruc-
tion. Mod ern im m u nologic crossm atch testing has nearly Hydration
elim inated hyp eracu te rejection. The d iagnosis and m an-
Inad equate hyd ration or failu re to m aintain normovolem ia
agem ent of these entities are d iscu ssed elsew here.
after an initial d iu resis m ay contribu te to renal d ysfunction
in the p ostop erative p eriod . Im m ed iate restoration of
Intrinsic Causes hyd rational statu s m ay resu lt in reinstitu tion of u rine flow,
Donor factors that m ay contribu te to an increased inci- and ad m inistration of crystalloid bolu ses is generally the
d ence of post-transplant oligoanu ria after d eceased d onor first intervention in the treatm ent of post-transplant oligoa-
transp lant inclu d e hyp ovolem ia second ary to hem orrhage nu ria. In this situ ation, attention m u st be p aid to the
or d iabetes insip id u s, hypotension, hypoxemia, high-d ose p atient’s card iovascu lar risk p rofile. If no increase in urine
vasoconstrictor therapy, and prolonged w arm ischem ia ou tp u t occu rs, su bsequ ent flu id m anagem ent m u st be
tim e. These m ay lead to renal inju ry either prior to or d u r- u nd ertaken w ith the recognition that many ischem ically
ing the renal recovery. Skilled d onor m aintenance is neces- inju red kid neys are not resp onsive to volu m e resu scitation,
sary u ntil the tim e of nep hrectom y to m inim ize the im p act and the p otential for volu m e overload , congestive heart
of these factors. As m entioned earlier, the u se of in situ aor- failu re, and need for early d ialysis exists if flu id is ad m inis-
tic perfu sion resu lts in virtually no w arm ischem ia tim e. In tered too aggressively.
general, longer p eriod s of cold p reservation, w hether by
sim ple hyp otherm ia or by pu lsatile perfu sion, resu lt in Perfusion
higher rates of p ost-transplant DGF (53). Failure of the previously mentioned strategies to generate
In the recip ient, long anastom otic tim e m ay contribu te u rinary ou tpu t d emand s investigation of the ad equacy of
to d elayed fu nction (54). Ad equate hyd ration and the u se allograft p erfu sion. The d iagnostic mod ality of choice is
of osm otic d iu retics have been show n to red u ce the inci- u ltrasonography w ith Dopp ler interrogation of the renal
d ence of DGF in recipients of kid neys from d eceased vessels and d etermination of the resistive ind ex (RI), w hich
d onors. For m ost recipients w ithou t p reexisting card iom y- is a m easu re of allograft p erfu sion (56). Since norm ally
opathies, this can be accom p lished w ithou t the need for renal blood flow continu es d u ring d iastole, the ratio of sys-
central venou s p ressure m onitoring. Volu m e load ing of 3 to tolic-to-d iastolic flow can be assessed using the Dopp ler
measurements of flow velocity in the transplant renal artery ■ Ureteral obstruction

and its branches. Defined by the formula [1– (systolic flow –
Incidence
diastolic flow )/ systolic flow ], the RI is increased at low d ias-
tolic flow velocities; the normal values are approxim ately 0.6 Obstru ction of the transp lant u reter is a rare com p lication of
to 0.8. Values approaching 1 (no d iastolic flow ) are sugges- renal transplantation, w ith rep orted incid ence ranging from
tive of increased renal resistance, and can be seen in Acute 1% to 7%. Althou gh a rare complication, u reteral obstruc-
Tubular N ecrosis (ATN ), rejection, or renal vein stenosis. tion greatly com plicates the m anagem ent of the transp lant
Reversal of diastolic flow is an ominous sign and suggests patient, ad d s enormou sly to the expense of the proced ure,
renal vein thrombosis. Low RIs are suggestive of renal artery and may ultimately resu lt in allograft loss or p atient d eath.
stenosis; how ever, this find ing is not uncommon early after Mund y et al. (62) reported a high operative mortality rate,
transplant, and may represent anastomotic ed em a. as high as 19%, w hen op erative intervention w as more com-
Radionuclide scanning with examination of time–activity mon, primarily d ue to sepsis. Urine in the obstructed sys-
cu rves can d em onstrate perfu sion abnorm alities and id en- tem m ay becom e infected , or the obstructed u reter m ay
tify failu re of excretory fu nction com p atible w ith acu te becom e necrotic; if infected u rine is spilled into the peri-
tu bu lar necrosis (57). In occasional cases, such stu d ies m ay transp lant space, the resultant local infection m ay be d iffi-
su ggest u rinary extravasation or obstru ction. cult to d iagnose and treat. The use of ultrasonography to
d iagnose obstruction and localized fluid collections has
Rejection marked ly improved the d iagnosis and management of the
Du ring the cou rse of post-transplant DGF, it is challenging transp lant p atient w ith a urologic com plication, and the u se
to id entify concom itant allograft rejection, since u rine ou t- of percutaneous interventional techniques has red uced the
pu t and creatinine are not reliable ind icators in this setting. associated morbid ity and mortality (66–70).
Therefore, p ercu taneous biopsy is ind icated at 7- to 14-d ay
Etiology
intervals. In this w ay, histologic evid ence of tu bu lar regen-
eration can be seen and occu lt rejection can be d iagnosed A w id e variety of op erative and p ostop erative cond itions
and ap p rop riately treated . m ay resu lt in obstru ction of the renal transp lant ureter. The
m ost com m on p roblem encou ntered is stenosis of the d istal
u reter (Fig. 47.3A) (62). This p roblem m ay be d ue to surgi-
■ Treatment cal error in p lacem ent of u reteral su tu res, ischemia of the
The management of post-transplant acute tubular necrosis is d istal u reter, im p rop er closu re of the su bm u scular tunnel,
primarily supportive. Dialysis therapy is continued as neces- hem atom a in the su bm u scu lar tu nnel, or angulation of the
sary. If oliguria is established, w hich is not responsive to fluid u reterovesical anastom osis. Obstru ctive fibrosis of the d is-
challenge, fluid administration should be restricted to meas- tal u reter occu rs as a late sequ ela of ischem ia, w hich, in
ured losses plus 500 mL/ day. Protein and potassium restric- tu rn, resu lts from d am aged or atherosclerotic blood su pply
tions may be necessary until allograft function improves. of the u reter or occasionally from rejection. Lymp hocele is a
The u nd erlying factors lead ing to acu te tu bu lar necrosis frequ ent cau se of renal transp lant u reter obstruction (62).
may be m ore im portant prognostically than the renal d ys- The m echanism of obstru ction typ ically involves angu la-
fu nction itself. Overall, the incid ence of DGF app ears to be tion of the u reterovesical ju nction or comp ression of the
low er am ong kid neys p reserved by p ulsatile perfu sion collecting system . Peritransp lant hem atom a m ay have the
than am ong those p reserved w ith sim p le hyp otherm ia sam e effect, and u reteral blood clots second ary to trau ma
(52,58). Am ong kid neys preserved by pu lsatile p erfu sion, incu rred at either kid ney recovery harvesting or im planta-
how ever, higher incid ences of DGF have been noted w ith tion have also been reported as a cause of early p ost-trans-
higher final pu m p systolic pressu res or term inal resistance p lant obstru ction (62). Rarely, the op erating surgeon m ay
measu rem ents (48). While graft su rvival rates are signifi- inad vertently position the ureter anterior to the sperm atic
cantly low er if early d ysfu nction occu rs (47,48,59), this is cord (71), rou nd ligam ent (62), or inferior ep igastric ves-
less true for kid neys from DCD d onors. sels, resu lting in obstru ction. Finally, stones in the trans-
p lanted u reter (62) and a fu ngu s ball, u su ally second ary to
cand id al infection of the u rine (72,73), have been reported
■ UROLOGIC COMPLICATIONS as rare cau ses of obstru ction.
In comparison w ith immunologic barriers, the apparent sim-
plicity of the renal transplant operation may at times lull the
operating surgeon into a sense of complacency regard ing
■ Diagnosis
this proced ure. It is particularly frustrating, how ever, to lose Ultrasonography is the mainstay of initial diagnosis of uro-
a kidney for technical reasons in the absence of rejection. logic complications follow ing transplantation because it is
Fortunately, this is a relatively rare occurrence. Urologic accurate, noninvasive, and does not rely on function of the
problems account for a large percentage of the technical transplant. Routine screening of all transplant patients w ith
complications that are encountered in renal transplantation. ultrasonography has, how ever, highlighted some pitfalls in
The reported incidence ranges from 3% to 14% (60–65). interpretation that should be emphasized . First, it is not at all
A B
FIGURE 47.3. A: Percutaneous nephrostogram demonstrating a tight stenosis at the ureteral anastomosis to the bladder.
B: Treatment of the stenosis with a percutaneously placed stent.
uncommon to diagnose mild hydronephrosis in the early involves p ercu taneou s antegrad e d ilatation of the u reteral
post-transplant period in a normal kidney transplant; the stricture (74). N ew er techniques includ e end oscopic
ultrasonographic appearance of dilated calyces and renal ureterostomy, or cutting of the strictu re, either throu gh the
pelvis probably results from the profound d iuresis occurring percu taneou s nep hrostomy or throu gh a cystoscopic
after transplantation. Further evaluation is warranted only if approach. Stand ard op erative repair, w hich is ind icated for
this find ing persists or w orsens in a setting of unsatisfactory long segm ental strictu res or those refractory to nonop era-
renal function. A second pitfall is that an obstructed ureter tive management, involves creation of a new u reterovesical
occasionally d oes not prod uce obvious hyd ronephrosis by anastomosis, usually w ith mobilization and resection of the
ultrasonographic examination. In these cases, the obstruc- involved u reter. If the op erative find ings are su ch that suffi-
tion is high, at the ureteropelvic junction, or prolonged cient viable transplant ureter is not available to reach the
obstruction has resulted in poor function w ith small vol- blad d er, the blad d er can be extensively mobilized and fixed
umes of urine. In this difficult situation, obstruction usually to the p soas mu scle to provid e ad d itional length, or a Boari
becomes a diagnosis by exclusion. In the absence of d ilated flap of blad d er can be ad vanced to replace the resected
calyces, antegrad e pyelography is more d ifficult. ureteral segment. A d ifficu lt but common situation may
arise w hen a patient’s blad d er is fou nd to be contracted ,
Treatment nonpliable, and trabecu lated . In this circu mstance, it may be
Treatm ent of the obstructed renal transplant ureter may be preferable to m obilize and remove the ipsilateral kid ney
simple or com plex, d epend ing on the cause and timing of and anastomose the remaining transplant u reter or renal
the obstruction. H ow ever, improvem ents in interventional pelvis to native u reter.
genitourinary rad iology have mad e this complication less Extensive local d rainage, nep hrostom y, and u rinary
emergent. Patients most frequently have a percutaneous catheter d rainage are u su ally ind icated after reop eration.
nephrostomy tube placed at the time of diagnosis and, there- Stenting the anastom osis w ith a soft d ou ble-J internal stent
fore, are not likely to be septic or uremic if surgery is neces- is also help fu l. Desp ite these m easu res, fu rther m orbid ity
sary (Fig. 47.3B). Und er these cond itions, the operating follow ing treatm ent of the obstru ction is frequ ent. In one
surgeon is more able to evaluate the problem carefully, map large series (62), 49% of p atients d evelop ed a fu rther u ro-
out a strategy, and proceed w ith all available resources. logic com plication (u sually u rinary fistula) after operative
Und er the sim plest of circu m stances, the obstruction is rep air of a p rim ary u rologic com p lication. This alarm ing
at the level of the d istal u reter. A nonoperative techniqu e statistic u nd erscores the im p ortance of p reventing u rinary
com plications throu gh the u se of proper techniqu e d u ring rejection commonly results in ureteral ischemia is not estab-
the organ p rocu rem ent and the p rim ary renal transp lant lished , but it seems a possibility because red uction in blood
op eration. flow to the transplant in general is w ell d ocumented during
acute rejection, and the delicate nature of the ureteral blood
supply makes it particularly vulnerable.
■ Urinary leak Ad equ ate blad d er d rainage w ith a urinary catheter is
The first few postoperative w eeks after renal transplantation imp ortant in p reventing p ostop erative leaks becau se the
are usually characterized by rapid red uction in the serum cre- p rofou nd d iu resis that often follow s transp lantation m ay
atinine and rapid elevation of the patient’s mood. Sometimes, p u t enormou s p ressu re on the new su tu re line if the blad -
how ever, the large urine volume of the first few postopera- d er cannot em p ty p rop erly. To avoid this p roblem , m ost
tive days falls off dramatically. The patient may report clear centers regu larly irrigate the catheter w ith sterile saline
drainage from the operative site and suprapubic pain or d is- solu tion in the im m ed iate p ostop erative p eriod . H ow ever,
comfort; fever and systemic sepsis may supervene. This clin- p rolonged catheter d rainage is not necessary and pred is-
ical situation, which is suggestive of a urinary leak, requires p oses to bacterial colonization of the blad d er and later u re-
rapid and accurate diagnosis and effective treatment. thral strictu re (75,76). It is necessary in the p reoperative
Urinary extravasation m ay occur anyw here from the evalu ation of the transplant recip ient to establish that p ro-
blad d er to the renal transplant calyx. The incid ence of static hyp ertrop hy or u rethral strictu re d oes not im p air
extravasation follow ing transplant has varied from 0.1% blad d er em ptying becau se these factors m ight also con-
(64) to 8.5% (63). The m ost com m on site is the d istal u reter tribute to early postoperative su tu re line d ehiscence.
at the u reteroneocystostom y. Pred isposing factors relate
prim arily to the blood su pply at this site and thu s involve Diagnosis
the d egree of trau m a at the tim e of procu rem ent, op erative Accurate d iagnosis is im portant because another renal
hand ling of the u reter at the tim e of the transplant proce- transp lant com p lication, lym p hocele, also m ay be mani-
d u re, the p resence of m ultiple renal arteries, and p ossibly fested by red u ced u rine ou tp u t and a p eritransp lant flu id
the intensity of the rejection process (2). collection. A p eritransp lant flu id collection observed on
The ureter usually leaks because it is ischemic. The rela- u ltrasonography should be aspirated if it is large ( 5 cm in
tively tenuous blood supply of the d istal ureter is vulnerable d iam eter) and accessible (Fig. 47.4). Patients should be
to operative trauma at the time of procurement and at reim- p laced on broad -sp ectru m antibiotics p rior to this proce-
plantation. Also, the ureter may become ischemic if a lower d u re. The flu id sp ecim en is sent for a creatinine d eterm ina-
polar artery has been inadvertently tied off or improperly tion. If a su fficient concentration grad ient exists betw een
anastomosed to the recipient blood vessels. Whether acute flu id and seru m creatinine, the d iagnosis of u rinary leak is
FIGURE 47.4. Ultrasound image of

a urinoma inferior to the renal allograft.
established and fu rther d iagnostic steps are u nd ertaken to ■ Pelvicalyceal leak

d efine the extent of the problem . If the fluid creatinine is
id entical to that of serum , it can be assu m ed that the flu id is Urinary extravasation at the calyx is rare and usually the
lym ph rather than u rine. Confirm atory cell counts and d if- result of trau m a to or occlusion of su bsegm ental arteries.
ferential analysis m ay be d one. An exception m ay occu r if Becau se there is no effective collateral arterial circu lation in
the d egree of renal fu nction is su ch that the kid ney m akes the kid ney, the resu lt m ay be either loss of renal
urine bu t d oes not clear creatinine, in w hich case this d if- p arenchym a w ith su bsequent fibrosis or necrosis and uri-
ferentiation is m ore d ifficult. nary extravasation. There is an association betw een this
If u rinary extravasation is su spected , a cystogram or com p lication and the p resence of m u ltip le renal arteries in
percutaneou s nep hrostom y is obtained . This m ay localize the d onor kid ney. Calyceal leaks tend to occu r later than
the leak to the blad d er, the ureterovesical anastomosis, or a u reteral or blad d er leaks and thu s m ay be hard er to d iag-
higher leak m ay be id entified . Percu taneous nep hros- nose and treat effectively. In one rep ort, seven of eight
togram s are the p roced u re of choice at the author ’s institu - p atients w ith this com plication u ltim ately lost the trans-
tion, as the ap p roach offers d iagnostic and therap eu tic p lant and three d ied (78). Treatm ent is p rolonged nephros-
value—if a leak is id entified , a nephrostom y tu be w ith tom y tu be d rainage throu gh the infarct into the involved
nep hrou reteral stent can be placed at the sam e tim e. Flexi- calyx if p ossible. Leakage from the renal p elvis is encoun-
ble fiberop tic cystoscop y w ith retrograd e cannulation of tered very rarely, p robably ow ing to its rich cap illary blood
the u reter is u su ally not an attractive op tion becau se m ost su p p ly. This com p lication m ay be associated w ith opera-
cases of urinary leak occur in the early post-transplant tive trau m a or, rarely, as a sp ontaneou s com p lication after
period , w hen d istension of the blad d er w ith a new su tu re transp lantation (79). In one series, sp ontaneou s ru pture of
line w ou ld not be ad visable. Also, w hen the u reteroneocys- the renal p elvis p resented from 5 to 46 d ays after transplan-
tostom y is p erform ed to the d om e of the blad d er, as in the tation and w as not associated w ith m echanical obstru ction.
popu lar Lich techniqu e, it is technically d ifficult to cannu - The cause of this com plication w as not obviou s in any case.
late the u reteral orifice even if it can be id entified . For One case w as su ccessfu lly treated w ith p rolonged nephros-
equivocal cases w here the pretest likelihood of a leak is tom y d rainage, bu t transp lant nep hrectom y w as required
low, rad ionu clid e scintigraphy (renal scan) is less invasive in three cases.
and can be u sed to ru le out the possibility of a leak (77).
Nonoperative management of urinary leaks is successful
in a majority of cases without further sequelae. Patients ■ LYMPHOCELE
require temporary nephrostomy for 2 to 6 months, depend-
ing on the size of the leak and the pace of healing. How ever,
■ Incidence
stricture formation requiring further therapy or late opera- A lym phocele is an extralym phatic collection of lym phatic
tive intervention occurs in up to 30% of cases where the initial flu id . Ow ing to the p elvic location of the renal transplant,
management is nonoperative (2). Any significant peritrans- an area rich in lym p hatics, lym p hocele is a com m on com -
plant urinoma should be separately drained. If ischemia of p lication of renal transp lantation. It is not clear w hat per-
the ureter has resulted in distal tissue loss and a large leak, centage of p eritransp lant flu id accu m u lations d evelop into
operative repair is necessary. Resection of the involved seg- clinically significant lym p hoceles requ iring intervention.
ment w ith reanastomosis or use of a Boari flap to reestablish Most transp lant su rgeons p refer to follow asym ptom atic
urinary continuity is usually performed. Cutaneous ureteros- collections exp ectantly u ntil sym p tom s or d eterioration of
tomy might theoretically be used, but in the context of renal renal fu nction m and ate op erative intervention. Clinically
transplantation, this procedure is not usually a satisfactory oriented series (80–84) have rep orted this com p lication to
long-term solution to the problem of ureteral necrosis. occu r in 0% to 22% of p atients. A lym p hocele typically
p resents later in the p ostoperative p eriod than u rinary
extravasation. The m ost com mon clinical p resentation is
■ Bladder leak abd om inal m ass (72%), ip silateral leg ed em a (58%), hyper-
The incid ence of leakage from the urinary bladder is 0% to tension (26%), clear d rainage from the w ou nd (19%), fever
4% (2,63,64). The opportunity for leakage is higher when the (19%), and d ecreasing u rine ou tp u t (15%) (85). The patient
Led better–Politano ureterovesical anastomosis is employed occasionally p resents w ith rap id p rogression to anu ria (86).
because this procedure involves a large cystostomy not The origin of the lym p hatic accum u lation m ay be from
required for the external ureteroneocystostomy. Our group recip ient lym p hatics severed at the time of su rgery, a con-
has reported a low rate of ureterovesical leak, approximately clu sion d raw n by lym p horad iograp hic stu d ies involving
3%, in ( 1,600 of the latter procedures (2). Another factor of injection of rad ionu clid e into the ip silateral leg of p atients
importance is the prior condition of the recipient bladder. If w ith this cond ition (87). H ow ever, a u niversal clinical
there have been multiple previous operative proced ures, the observation is that lym p hoceles either p resent or greatly
risk of leakage is higher. Most bladder leaks can be repaired enlarge d u ring a rejection ep isod e, su ggesting that renal
primarily or treated conservatively with local drains and hilar lym p hatics of the allograft contribu te lym p h to the
prolonged urinary catheterization. lym p hocele as w ell (88).
tomy to decrease lymph leakage from this source, this is

impractical for laparoscopic nephrectomy.
■ SUPERFICIAL WOUND INFECTION

With the increasing su ccess and availability of kid ney
transp lantation, infection of the su p erficial transp lant
w ou nd is increasing in incid ence, as the sp ectru m of p re-
d isp osing factors grou p ing kid ney recip ients has exp and ed
over tim e. When the u rine is sterile p reop eratively, the
transplant w ou nd is consid ered a clean-contam inated
w ou nd . While Belzer et al. (91) in the 1970s rep orted an
infection rate of ( 1%, m ore recent review s report higher
FIGURE 47.5. High-magnification ultrasound image of a lymphocele that infection rates, as high as 15% (92–94). The increase in
demonstrates fine linear septations not typically seen in ultrasound imaging of w ou nd infection rates, d esp ite the existence of m ore spe-
urinoma or abscess.
cific im m u nosu p p ression, is likely a consequ ence of
increased level of com orbid ities present in current kid ney
transp lant recip ients, esp ecially w ith resp ect to obesity and
■ Diagnosis d iabetes, althou gh higher infection rates have been
The d iagnosis of lymphocele has been greatly facilitated by rep orted w ith the u se of sirolim u s (94). In a recent large sin-
the w id espread use of d iagnostic ultrasonography. Lympho- gle center stu d y, obesity, recip ient age, and DGF w ere asso-
celes typically d emonstrate fine linear septations not seen ciated w ith an infectiou s w ou nd com p lication (92). When
w ith urinoma or abscess (Fig. 47.5). Careful aspiration und er infection d oes occu r, Gram -p ositive organism s are m ost
sterile cond itions w ith antibiotic coverage is routinely per- com m only cu ltu red .
form ed to establish the d iagnosis and rule out urinoma. Prevention of superficial wound infection relies on the
meticulous operative technique and administration of pro-
Treatment phylactic antibiotics. Tissue should be handled gently, and
The treatment of lymphocele may be conservative at first, care should be taken to avoid hematoma in the subcutaneous
consisting of complete aspiration und er ultrasonographic tissue. Copious irrigation of the wound with w arm saline
guid ance. Occasionally, this therapy is all that is required . before closure of the skin may be beneficial. Diagnosis of
Aspiration should not be repeated as infection may result. superficial w ound infection obligates the surgeon to investi-
External d rainage will usually require a prolonged course gate the possibility that a perinephric infection exists as well.
and carries the risk of infection. The use of sclerosing agents
as an adjunct to external drainage, which dramatically short-
ens the period of d rainage, has been reported (89,90). The
■ PERINEPHRIC ABSCESS
mean d uration from external d rainage to complete cessation Su bfascial p eritransp lant infection is an u nu su al bu t p oten-
of d rainage w as 4.5 w eeks. Internal d rainage is the treatment tially grave comp lication of renal transp lantation. The clin-
of choice in m ost centers. A peritoneal w ind ow from the ical presentation w ith fever and oliguria m im ics rejection,
lymphocele cavity into the peritoneum is created either w ith and catastrop hic resu lts are certain if an u nd erlying abscess
open or laparoscopic technique so that peritransplant lymph is treated w ith increased im mu nosu p p ression. Aggressive
has free egress into, and can be reabsorbed by, the peritoneal and thorou gh evalu ations of p atients w ith a su ggestive his-
membrane. Care should be taken to make the w ind ow large tory are im portant.
enough so that bow el cannot become incarcerated in it, and Peritransp lant abscess has been reported to be associ-
to minimize the risk of reperitonealization of the d efect and ated w ith peritransp lant hematoma (95–98), post-transplant
recurrence of the lymphocele. Also, the transplant ureter fre- u rinary fistu la (95), the presence of infected u rine at the time
quently is incorporated into the medial (operated ) w all of of transplantation (99), and the u se of an ileal cond uit
the lymphocele, and ureteral injury d uring this proced ure (100,101) for u rinary d iversion. Other factors pred isposing
has been reported (84). to abscess form ation are m ore general and inclu d e the u se
Certain technical maneuvers at the original transplant of imm unosup pressive d ru gs, poor nutritional status of the
procedure may be helpful in preventing lymphoceles. First, transp lant recipient, obesity, and the location of the trans-
most of the large lymphatics coursing from the leg follow the plant incision in the groin area. The d iagnosis is mad e by
external iliac artery and vein. These can be easily moved out u ltrasonography-gu id ed need le aspiration of fluid collec-
of harm’s w ay. If d ivision of large visible lymphatics is nections in the appropriate clinical context. The ultrasono-
essary, ligation may be preferable to electrocautery because grap hic appearance of the abscess itself is not particularly
lymphatics do not coagulate well as do blood vessels. While characteristic, but particulate d ebris is occasionally noted
meticulous ligation of lymphatics near the transplant hilum (68) and multiple linear septations such as those that w ould
w as employed by som e surgeons in the era of open nephrec- be seen in a lym phocele are not p resent.
Immed iate transplant nephrectomy w ith w id e w ound Whether the transp lant can be saved follow ing fractu re
d rainage may be required if sepsis is extensive, but percuta- d ep end s on the clinical circu m stances and op erative find -
neous or operative d rainage alone is usually satisfactory if ings. If the fractu red area is shallow, there m ay be som e
the infection is localized and not associated w ith system ic m erit in rep airing the kid ney w ith p led geted su tu res or
sepsis. Althou gh the location m ay raise concern abou t the m esh, as has been rep orted (108,109). H ow ever, in most cir-
development of a pseudoaneurysm at the arterial anastomo- cu m stances, rejection is ad vanced at the tim e of ru pture
sis, this, in fact, rarely occurs. Immunosuppression can gener- and transp lant nep hrectom y is the w isest alternative, in
ally be drastically red uced in the setting of sepsis w ithout conju nction w ith carefu l and thorou gh evacu ation of the
immediate loss of the allograft. Long-term treatment with resu ltant p eritransp lant hem atom a.
broad -sp ectru m antibiotics is ind icated . The offend ing
organisms are Gram positive in one-half of cases (99). Multi-
ple organisms may be cultured from as many as 30%. The
■ HYPERCALCEMIA
most common organisms encountered are coagulase-positive Virtually all patients with chronic renal failure have second-
Staphylococcus aureus and Escherichia coli. ary hyperparathyroidism as the result of inability to produce
Measu res to avoid this com p lication shou ld be u nd er- 1,25-di-hydroxyvitamin D, renal phosphate retention, and
taken at several levels. Transp lant d onors w ith generalized extracellular complexing of circulating calcium. After suc-
sepsis and active u rinary tract infections shou ld be ad e- cessful renal transplantation, postoperative hypercalcemia is
qu ately treated w ith antibiotics p rior to d onation. Donors not uncommon. When the hypercalcemia is resistant to phos-
and recip ients shou ld receive p reop erative antibiotics, and phate repletion, this condition has been referred to as tertiary
seriou s attem p ts at erad icating recip ient u rinary tract post-transplant hyperparathyroidism, suggesting that the
infection shou ld be m ad e p reop eratively, either w ith long- hypertrophic parathyroid glands have become autonomous.
term antibiotics or p retransp lant native nep hrectom y if the True adenomatous degeneration is rare (110) but parathyroid
sou rce of infection is w ithin the kid ney. The blad d er hyperplasia may persist for prolonged periods of time even
shou ld be irrigated w ith p ovid one–iod ine or antibiotic w ith a well-functioning transplant.
solution ju st p rior to op ening the blad d er intraop eratively, Early p ost-transp lant hyp ercalcem ia occu rs in u p to
and the transp lant w ou nd shou ld be thorou ghly irrigated 28.6% of renal transp lant recip ients (111). The m ost im por-
on com p letion of all anastom oses. In m any cases, the tant etiologic factor appears to be slow resolution of hyper-
organism isolated from the p eritransp lant infection is active p arathyroid fu nction in com bination w ith increased
id entical to the organism cu ltu red p reop eratively from the absorp tion of calciu m as the resu lt of restored 1,25-d ihy-
recip ient u rine (99). d roxyvitam in D activity (112). In ad d ition, renal transplant
A very u nusual presentation of p eritransplant abscess is recipients are com m only phosp hate d epleted in the p ost-
ruptu re of the infected fluid into the peritoneal cavity w ith op erative p eriod , a factor that contribu tes to hypercal-
the d evelop m ent of peritonitis (99,102). This d evelop m ent cem ia. Cu rrent p ractice is to treat conservatively w ith
has an associated m ortality of 80% (102). aggressive d iu resis and elim ination of p hosp hate-bind ing
antacid s.
In m ost cases, excess p arathyroid function su bsid es
■ ALLOGRAFT FRACTURE
enough in the post-transplant period to avoid long-term
Fractu re of the renal allograft is rare. Fracture historically hypercalcemia. Some patients d o d evelop long-term hyper-
has occu rred late in the cou rse of an ep isod e of acu te rejec- calcemia if the hypertrophic gland s fail to involute (111).
tion w hen the p atient has retu rned to d ialysis (103–108). This cond ition m ay persist and , d epend ing on the severity
The p atient p resents w ith p ain at the site of the transp lant of the hypercalcemia, may ad versely influence transp lant
and w ith hyp otension. Operative find ings vary, bu t in most function (112). Subtotal parathyroid ectomy should be
reported series, the fractu re is linear, shallow, and located reserved for those hyperparathyroid p atients w ho have
on the convex su rface of the kid ney. seru m calciu m in excess of 12.5 m g p er d L or w ho experi-
The incid ence of allograft fracture ranges from 0.14% to ence persistent symptoms (113).
8.5%, w ith the tru e figu re likely very low, and the incid ence
has d ecreased as rates of severe rejection have d rop ped
over the d ecad es. This com plication is related to severe
■ REFERENCES
sw elling of the kid ney d u ring acu te rejection, but it has 1. Garcia-Rinald i R, Lefrak EA, Defore WW, et al. In situ p reservation of
cad aver kid neys for transp lantation. Ann Surg 1975;182:576.
been su ggested that anticoagulation d u ring hem od ialysis 2. Englesbe MJ, Dubay DA, Gillespie BW, et al. Risk factors for urinary com-
may contribu te to the bleed ing as w ell. It is interesting that plications after renal transplantation. Am J Transplant 2007;7:1536–1541.
fractu re of the native kid ney has been reported in cond i- 3. Rosenthal JT, Shaw BW Jr, H ard esty RL, et al. Princip les of m u ltip le
organ procu rem ent from cad aver d onors. Ann Surg 1983;198:617.
tions su ch as hyd ronephrosis and pregnancy, in patients 4. Sahani DV, Rastogi N , Greenfield AC, et al. Mu lti-d etector row CT in
receiving anticoagu lant therap y, and in association w ith evalu ation of 94 living renal d onors by read ers w ith varied exp eri-
renal vein throm bosis, ind icating that the mechanism s ence. Radiology 2005;235(3):905–910.
5. Kaw am oto S, Montgom ery RA, Law ler LP, et al. Mu ltid etector CT
involved are not solely related to imm u nologic aspects of angiograp hy for preop erative evaluation of living laparoscop ic kid -
the rejection p rocess. ney d onors. Am J Roentgenol 2003;180:1633–1638.
6. Ratner LE, Kavou ssi LR, Schu lam PG, et al. Com p arison of lap aro- 32. Gu z G, Yuksel A, Onal B, et al. Selective em bolization in the m anage-
scopic live d onor nephrectom y versu s the stand ard op en app roach. m ent of arteriovenous fistula after renal allograft biopsy preserves
Transplant Proc 1997;29:138. renal allograft fu nction. Int Urol Nephrol 2005;37(1):207–208.
7. Flow ers JL, Jacobs S, Cho E, et al. Com p arison of op en and live d onor 33. Lacom be M. Arterial stenosis com p licating renal allotransp lantation
nephrectom y. Ann Surg 1997;226:483. in m an: a stu d y of 38 cases. Ann Surg 1975;181:283.
8. Wolf JS Jr, Marcovich R, Merion RM, et al. Prosp ective, case-m atched 34. Dim itroulis D, Bokos J, Zavos G, et al. Vascular com p lications in renal
com parison of hand -assisted laparoscopic and open surgical live transplantation: a single-center experience in 1367 renal transp lanta-
d onor nephrectom y. J Urol 2000;163:1650–1653. tions and review of the literatu re. Transplant Proc 2009;41(5):1609–1614.
9. Sm ith JM, Stablein D, Singh A, et al. Decreased risk of renal allograft 35. Polak WG, Jezior D, Garcarek J, et al. Incid ence and ou tcom e of trans-
throm bosis associated w ith interleu kin-2 recep tor antagonists: a plant renal artery stenosis: single center exp erience. Transplant Proc
rep ort of the N APRTCS. Am J Transplant 2006;6(3):585–588. 2006;38(1):131–132.
10. Englesbe MJ, Pu nch JD, Arm strong DR, et al. Single-center stu d y of 36. Fernand ez-N ajera JE, Beltran S, Ap aricio M, et al. Transp lant renal
technical graft loss in 714 consecu tive renal transp lants. Transplanta- artery stenosis: association w ith acu te vascu lar rejection. Transplant
tion 2004;78(4):623–626. Proc 2006;38(8):2404–2405.
11. Iw am i D, H arad a H , Miu ra M, et al. Su ccessfu lly rescu ed renal graft 37. Dickerm an RM, Peters PC, H u ll AR, et al. Su rgical correction of p ost-
artery throm bosis by ex vivo throm bectom y: a case rep ort. Transplant transp lant renovascu lar hyp ertension. Ann Surg 1980;192:639.
Proc 2009;41(5):1951–1953. 38. Rid gw ay D, White SA, N ixon M, et al. Prim ary end olu m inal stenting
12. Libicher M, Rad eleff B, Grenacher L, et al. Interventional therap y of of transplant renal artery stenosis from cad aver and non-heart-beat-
vascu lar com p lications follow ing renal transp lantation. Clin Trans- ing d onor kid neys. Clin Transplant 2006;20(3):394–400.
plant 2006;20(Su p p l 17):55–59. 39. VanSon WJ, Vand erSlikke LB, H oorntje SJ. Cap top ril-ind u ced d eterio-
13. Rouviere O, Berger P, Beziat C, et al. Acu te throm bosis of renal trans- ration of graft function in patients w ith a transplant renal artery
plant artery: graft salvage by m eans of intra-arterial fibrinolysis. stenosis. Proc Eur Dial Transplant Assoc 1983;20:325.
Transplantation 2002;73(3):403–409. 40. Gao J, N g A, Shih G, et al. Intrarenal color d u p lex u ltrasonograp hy: a
14. Ku syk T, Verran D, Stew art G, et al. Increased risk of hem orrhagic w ind ow to vascu lar com p lications of renal transp lants. J Ultrasound
com plications in renal allograft recipients receiving system ic heparin Med 2007;26(10):1403–1418.
early posttransp lantation. Transplant Proc 2005;37(2):1026–1028. 41. Lanzm an RS, Voicu lescu A, Walther C, et al. ECG-gated nonenhanced
15. Osm an Y, Shokeir A, Ali-el-Dein B. Vascu lar com p lications after live 3D stead y-state free p recession MR angiograp hy in assessm ent of
d onor renal transp lantation: stu d y of risk factors and effects on graft transplant renal arteries: com p arison w ith DSA. Radiology 2009;252(3):
and p atient su rvival. J Urol 2003;169(3):859–862. 914–921.
16. Potti A, Danielson B, Sen K. Tru e m ycotic aneu rysm of a renal artery 42. Papp as P, Zavos G, Kaza S, et al. Angiop lasty and stenting of arterial
allograft. Am J Kidney Dis 1998;31(1):E3. stenosis affecting renal transp lant fu nction. Transplant Proc 2008;40(5):
17. Mathis AS, Dave N , Shah N K, et al. Bleed ing and throm bosis in high- 1391–1396.
risk renal transplantation cand id ates u sing hep arin. Ann Pharmacother 43. Peregrin JH , Stribrna J, Lacha J, et al. Long-term follow -u p of renal
2004;38(4):537–543. transp lant p atients w ith renal artery stenosis treated by p ercu taneou s
18. Sienko J, Tejchm an K, Cnotliw y M, et al. Crossed byp ass fem oro- angiop lasty. Eur J Radiol 2008; 66(3):512–518.
fem oralis in patient w ith external iliac artery occlusion in the cou rse 44. Peregrin JH , Bu rgelova M. Restoration of failed renal graft fu nction
of sep tic hem orrhage after renal graft exp lantatation. Ann Transplanta- after su ccessfu l angiop lasty of p ressu re-resistant renal artery stenosis
tion 2006;11(3):12–14. using a cu tting balloon: a case rep ort. Cardiovasc Intervent Radiol
19. Pfund stein J, Roghm ann MC, Schw albe RS, et al. A rand om ized trial 2009;32(3):548–553.
of surgical antim icrobial prophylaxis w ith and w ithou t vancom ycin 45. H enning BF, Ku chlbau er S, Boger CA. Percu taneou s translu m inal
in organ transp lant p atients. Clin Transplant 1999;13:245–252. angiop lasty as first-line treatm ent of transp lant renal artery stenosis.
20. Merion RM, Calne RY. Allograft renal vein throm bosis. Transplant Proc Clin Nephrol 2009;71(5):543–549.
1985;17:1746. 46. H agen G, Wad strom J, Magnu sson M, et al. Ou tcom e after p ercu ta-
21. Salehip our M, Salahi H , Jalaeian H , et al. Vascu lar com p lications fol- neous translum inal angioplasty of arterial stenosis in renal transplant
low ing 1500 consecu tive living and cad averic d onor renal transp lan- patients. Acta Radiologica 2009;50(3):270–275.
tations: a single center stu d y. Saudi J Kid Dis Transplant 2009;20(4): 47. Moers C, Kornm ann N S, Leu venink H G, et al. The influ ence of
570–572. d eceased d onor age and old -for-old allocation on kid ney transp lant
22. Melam ed ML, Kim H S, Jaar BG, et al. Com bined p ercu taneou s ou tcom e. Transplantation 2009;88(4):542–552.
m echanical and chem ical throm bectom y for renal vein throm bosis in 48. Cecka JM. Kid ney Transp lantation in the United States. In: Clinical
kid ney transp lant recip ients. Am J Transplant 2005;5(3):621–626. Transplants 2008, Cecka JM, Terasaki PI, Ed s. UCLA Tissue Typing Lab-
23. Sterrett SP, Mercer D, Johanning J, et al. Salvage of renal allograft oratory, p p 1–18.
using venou s throm bectom y in the setting of iliofem oral venou s 49. Barlow AD, Metcalfe MS, Johari Y, et al. Case-m atched com p arison of
throm bosis. Nephrol Dial Transplant 2004;19(6):1637–1639. long-term results of non-heart beating and heart-beating d onor renal
24. Alkhunaizi AM, Olyaei AJ, Barry JM. Efficacy and safety of low transplants. Br J Surg 2009;96(6):685–691.
m olecular w eight hep arin in renal transp lantation. Transplantation 50. Yarlagadda SG, Coca SG, Formica RN Jr, et al. Association between
1998;66(4):533–534. delayed graft function and allograft and patient survival: a systematic
25. Allen RD, Michie CA, Mu rie JA, et al. Deep venou s throm bosis after review and meta-analysis. Nephrol Dial Transplantat 2009;24(3):1039–1047.
renal transplantation. Surg Gynecol Obstet 1987;164(2):137–142. 51. N ogu eira JM, H aririan A, Jacobs SC, et al. The d etrim ental effect of
26. Matas AJ, Sibley R, Mau er M, et al. The valu e of need le renal allograft poor early graft function after laparoscopic live d onor nep hrectom y
biopsy. I. A retrosp ective stu d y of biop sies p erform ed d u ring p u tative on graft ou tcom es. Am J Transplant 2009;9(2):337–347.
rejection episod es. Ann Surg 1983;197:226. 52. Su ng RS, Christensen LL, Leichtm an AB, et al. Determ inants of d is-
27. Rohr MS. Renal allograft acu te tu bu lar necrosis. II. A light and elec- card of exp and ed criteria d onor kid neys: Im p act of biopsy and
tron m icroscop ic stu d y of biop sies taken at p rocu rem ent and after m achine perfusion. Am J Transplant 2008;8:783–792.
revascu larization. Ann Surg 1983;197:663. 53. H etzel GR, Klein B, Brau se M, et al. Risk factors for d elayed graft
28. Manno C, Strip poli GFM, Arnesano L, et al. Pred ictors of bleed ing function after renal transplantation and their significance for long-
com plications in p ercu taneou s u ltrasou nd -gu id ed renal biopsy. Kid- term clinical outcom e. Transpl Int 2002;15:10–16.
ney Int 2004;66:1570–1577. 54. Shim shak RR, H attner RS, Tu cker C, et al. Segm ental acu te tu bu lar
29. H ergesell O, Felten H , And rassy K, et al. Safety of u ltrasound -gu id ed necrosis in kid neys w ith m u ltiple renal arteries transplanted from liv-
percutaneous renal biop sy—retrosp ective analysis of 1090 consecu - ing-related d onors. J Nucl Med 1977;18:1074.
tive cases. Nephrol Dial Transplant 1998;13:975–977. 55. Provoost AP, Kap tein L, VanAken M. N ep hrotoxicity of cyclosp orine
30. Debru yn e FMJ, Koen e RAP, Moon en WA, et al. In traren al arteri- A in rats w ith a d im inished renal fu nction. Clin Nephrol 1986;25:S162.
oven ou s fistu la follow in g ren al allograft biop sy. Eur Urol 1978;4: 56. Baxter GM. Ultrasound of renal transp lantation. Clin Radiol 2001;56:
435. 802–818.
31. Baquero A, Morris MC, Cop e C, et al. Selective em bolization of vascu- 57. Diethelm AG, Dubovsky EV, Whelchel JD. Diagnosis of impaired renal
lar com plications follow ing renal biopsy of the transplant kid ney. function after kid ney transplantation using renal scintigraphy, renal
Transplant Proc 1985;17:1751. plasma flow and urinary excretion of hippurate. Ann Surg 1980;191:604.
58. Wight J, Chilcott J, H olm es M, et al. The clinical and cost-effectiveness 86. Diethelm AG. Anu ria second ary to p erirenal lym p hocele: a com p lica-
of pu lsatile m achine p erfu sion versu s cold storage of kid neys for tion of renal transp lantation. South Med J 1972;65:350.
transplantation retrieved from heart-beating and non-heart-beating 87. Ward K. The origin of lym p hoceles follow ing renal transp lantation.
d onors. Health Technol Assess 2003;7:1–94. Transplantation 1978;25:346.
59. Ged d es CC, Woo YM, Jard ine AG. The im p act of d elayed graft fu nc- 88. Cockett ATK, N etto KV. Increased lym p hatic d rainage from renal
tion on the long-term ou tcom e of renal transp lantation. J Nephrol 2002; transplant. Urology 1973;2:571.
15:17–21. 89. Tasar M, Gulec B, Saglam M. Posttransp lant sym p tom atic lym p hocele
60. Li Marzi V, Filocam o MT, Dattolo E, et al. The treatm ent of fistu lae and treatm ent w ith percutaneous d rainage and ethanol sclerosis: long-
ureteral stenosis after kidney transplantation. Transplant Proc 2005;37(6): term follow -up . Clin Imaging 2005;29(2):109–116.
2516–2517. 90. Silas AM, Forau er AR, Perrich KD, et al. Sclerosis of p ostop erative
61. Karam G, Maillet F, Parant S, et al. Ureteral necrosis after kid ney lym phoceles: avoid ance of prolonged catheter d rainage w ith use of a
transp lantation: risk factors and im p act on graft and p atient su rvival. fibrin sealant. J Vasc Interv Radiol 2006;17(11 Pt 1):1791–1795.
Transplantation 2004;78(5):725–729. 91. Belzer FO, Salvatierra O, Schw erzer RT, et al. Prevention of w ou nd
62. Mu nd y MR, Pod esta ML, Bew ick M, et al. The u rological com p lica- infection by top ical antibiotics in high risk p atients. Am J Surg 1973;
tions of 1000 renal transp lants. Br J Urol 1981;53:397. 126:180.
63. Lau ghlin KR, Tilney N L, Richie JP. Urologic com p lications in 718 renal 92. Lynch RJ, Ranney DN , Shijie C, et al. Obesity, su rgical site infection,
transp lant patients. Surgery 1984;95:297. and ou tcom e follow ing renal transp lantation. Ann Surg 2009;250(6):
64. Santiago-Delpin EA, Baqu ero A, Gonzalez Z. Low incid ence of uro- 1014–1020.
logic com p lications after renal transplantation. Am J Surg 1986;151:374. 93. Menezes FG, Wey SB, Peres CA, et al. Risk factors for su rgical site
65. Ohl DA, Konnak JW, Cam p bell DA Jr, et al. Extravesical u reteroneo- infection in kid ney transp lant recip ients. Infect Control Hosp Epidemiol
cystostom y in renal transp lantation. J Urol 1988;139:499. 2008;29(8):771–773.
66. Koehler PR, Kanenafo H H , Maxw ell JC. Ultrasonic “B” scanning in 94. Trop pm ann C, Pierce JL, Gand hi MM, et al. H igher su rgical w ou nd
the d iagnosis of com p lications in renal transp lant p atients. Radiology com plication rates w ith sirolim us im m u nosupp ression after kid ney
1976;119:661. transp lantation: a m atched -p air p ilot stu d y. Transplantation 2003;76(2):
67. Morley P, Barnett E, Bell PRF, et al. Ultrasou nd in the d iagnosis of flu id 426–429.
collections follow ing renal transplantation. Clin Radiol 1975;26:199. 95. Kyriakid es GK, Sim m ons RL, N ajarian JS. Wou nd infections in renal
68. Silver TM, Cam p bell DA Jr, Wicks JD, et al. Peritransp lant flu id collec- transp lant w ou nd s: p athogenetic and p rognostic factors. Ann Surg
tions: u ltrasonic evalu ation and clinical significance. Radiology 1981; 1975;182:770.
138:145. 96. Lee H M, Mad ge GE, Mend ez-Picon G, et al. Su rgical com p lications in
69. Bhagat VJ, Gord on RL, Osorio RW. Ureteral obstru ctions and leaks renal transp lant recipients. Surg Clin North Am 1978;58:285.
after renal transplantation: ou tcom e of p ercu taneou s antegrad e 97. Schw erzer RT, Kou ntz SL, Belzer FO. Wou nd com p lications in recip i-
u reteral stent placem ent in 44 p atients. Radiology 1998;209(1):159–167. ents of renal transp lants. Ann Surg 1973;177:58.
70. Alcaraz A, Bujons A, Pascu al X. Percu taneou s m anagem ent of trans- 98. Starzl TE, Groth CG, Putnam CW, et al. Urologic com p lications in 216
p lant u reteral fistu lae is feasible in selected cases. Transplant Proc 2005; hu m an recip ients of renal transp lants. Ann Surg 1970;172:1.
37(5):2111–2114. 99. Lorber MI, Cam p bell DA Jr, Konn ak JW, et al. Etiology an d m an age-
71. Karm i SA, Dagher FJ, Ram os E, et al. Sp erm atic cord : cau se of ureteral m ent of early and late p eritransp lant infections. J Urol 1982;127:
obstru ction in renal allograft recip ients. Urology 1978;11:380. 870.
72. Ireton RC, Krieger JN , Ru d d TG, et al. Percu taneou s end oscop ic treat- 100. Lartro JE, Mu stapha N , Mee AD, et al. Ileal u rinary d iversion in
m ent of fu ngus ball obstru ction in a renal allograft. Transplantation p atients w ith renal transp lants. Br J Urol 1975;47:603.
1985;39:453. 101. Markland C, Kelly WD, Bu selm eier T, et al. Renal transp lantation into
73. Walzer Y, Bear RA. Ureteral obstru ction of renal transp lant d u e to iliac u rinary cond u its. Transplant Proc 1972;4:629.
u reteral cand id iasis. Urology 1983;21:295. 102. H an T, VanH ook EJ, Sim m ons RL, et al. Prognostic factors of p eri-
74. Lieberm an RP, Glass N R, Cru m m y AB, et al. N on-op erative p ercu ta- toneal infections in transp lant p atients. Surgery 1978;84:403.
neous m anagem ent of urinary fistu las and strictures in renal trans- 103. Martinez Mansu r R, Piana M, Cod one J, et al. The ru p tu re of the renal
p lantation. Surg Gynecol Obstet 1982;155:667. graft. Archivos Espanoles de Urologia 2006;59(5):489–492.
75. Loening SA, Banow sky LH , Brau n WE, et al. Blad d er neck contracture 104. Shahrokh H , Rasou li H , Zargar MA, et al. Sp ontaneou s kid ney allo-
and ureteral stricture as com p lications of renal transp lantation. J Urol graft rup ture. Transplant Proc 2005;37(7):3079–3080.
1975;114:688. 105. Lee H M. Su rgical techniqu es of renal transp lantation. In: Morris PJ,
76. N erstrom B, Brix E, Clau sen E, et al. Late u rological com p lications fol- ed . Kidney transplantation, principles and practice. N ew York: Gru ne &
low ing hum an kid ney transp lantation. Acta Clin Scand Suppl 1973; Stratton; 1979.
433:113. 106. Sanchez d e la N ieta MD, Sanchez-Fru ctu oso AI, Alcazar R, et al.
77. Rosenberg RJ, Schw eizer RT, Sp encer RP. Ureteral leak after renal H igher graft salvage rate in renal allograft ru pture associated w ith
transp lantation. Clin Nucl Med 1999;24(6):440–442. acu te tu bu lar necrosis. Transplant Proc 2004;36(10):3016–3018.
78. Gold m an MN , Bu rleson RL, Tilney N L. Calyceal–cu taneou s fistu lae 107. Richard son AJ, H iggins RM, Jaskow ski AJ. Sp ontaneou s ru p tu re of
in renal transp lant p atients. Ann Surg 1976;184:679. renal allografts: the im portance of renal vein throm bosis in the
79. Kogan BA, Konnak JW, MacGregor RJ, et al. Sp ontaneou s ru p tu re of cyclosp orin era. Br J Surg 1990;77(5):558–560.
renal pelvis after renal transp lantation. Urology 1981;18:456. 108. Gand y R, Asthana S, Menon KV, et al. The u se of p olyglactin 910 m esh
80. Said i RF, Wertheim JA, Ko DS, et al. Im p act of d onor kid ney recovery to obtain haem ostasis and prevent further splitting in a fractu red
m ethod on lym phatic com p lications in kid ney transp lantation. Trans- transp lant kid ney. Ann R Coll Surg Engl 2006;88(6):590–591.
plant Proc 2008;40(4):1054–1055. 109. Drybu rgh P, Porter KA, Krom RAF, et al. Shou ld the ru p tu red renal
81. Derw eesh IH , Ism ail H R, Gold farb DA, et al. Intraop erative placing of allograft be rem oved ? Arch Surg 1979;114:850.
d rains d ecreases the incid ence of lym p hocele and d eep vein throm bo- 110. Diethelm AG, Ed w ard s RP, Whelchel JD. The natu ral history and su r-
sis after renal transp lantation. BJU Int 2008;101(11):1415–1419. gical treatm ent of hyp ercalcem ia before and after renal transp lanta-
82. Zietek Z, Sulikow ski T, Tejchm an K. Lym p hocele after kid ney trans- tion. Surg Gynecol Obstet 1982;154:481.
p lantation. Transplant Proc 2007;39(9):2744–2747. 111. Parfitt AM. H yp ercalcem ic hyp erp arathyroid ism follow ing renal
83. Sm yth GP, Beitz G, Eng MP, et al. Long-term ou tcom e of cad averic transplantation and com plications for population control in the
renal transplant after treatm ent of sym p tom atic lym p hocele. J Urol p arathyroid gland . Miner Electrolyte Metab 1982;8:92.
2006;176(3):1069–1072. 112. McCarron DA, Ben nett WM, Mu th er RS, et al. Post-tran sp lan t
84. H am za A, Fischer K, Koch E, et al. Diagnostics and therapy of lym pho- h yp erp arath yroid ism d em onstration of retained control of
celes after kid ney transp lantation. Transplant Proc 2006;38(3):701–706. p arath yroid fu n ction by ion ized calciu m . Am J Clin Nutr 1980;33:
85. Brooks JG, H u lbert JC, Patel AS, et al. The d iagnosis and treatm ent of 1536.
lym phoceles associated w ith renal transp lantation. A rep ort of six 113. David DS, Sakai S, Brennan L. H yp ercalcem ia after renal transp lanta-
cases and a review of the literatu re. Br J Urol 1978;50:307. tion. Long-term follow -u p d ata. N Engl J Med 1973;289:398.
CHAPTER
48
Complications of Liver Transplantation

Shawn J . Pelletier
■ INTRODUCTION are available for vascu lar reconstru ction. Laceration of the
p ortal vein can be rep aired u sing a segm ent of d onor iliac
Liver transplantation is the treatment of choice for patients vein or inferior vena cava (IVC), w hile inju ries to the arte-
with end-stage liver disease due to a variety of disorders as rial su p p ly m ay be salvaged u sing d onor iliac arterial
well as for patients with severe acute liver failure. This life- grafts (7). Inju ry to the su p rahep atic IVC cu ff m ay occu r
saving procedure is primarily limited by the number of avail- and can be reconstru cted w ith an end -to-end extension
able organs. Graft and patient survival rates have increased graft u sing the infrahep atic IVC from the sam e d onor (8).
gradually since the 1980s (1). At present, the average 1-year Althou gh em barrassing, the need to reconstru ct the hepatic
patient survival rate in the United States is approaching 90% arterial circu lation of a d onor liver shou ld not cause u nd u e
(2). Patients w ho survive the first year typically have rela- concern, given that reconstru ction of a replaced right
tively low mortality rates thereafter (3,4) and current 10-year hepatic artery or other aberrant vessel is frequently neces-
patient survival is 60% (2). Early death and graft loss can sary d esp ite the finest su rgical techniqu e and a satisfactory
largely be traced to complications that occur at the time of ou tcom e can be exp ected (7).
transplantation or in the perioperative period, whereas late
death is usually due to the cardiovascular d isease or the
development of immunosuppression-related infection or ■ PRIMARY NONFUNCTION
malignancy (3,4). Much of the improvement in early mortal- Prim ary nonfu nction of the allograft is the single m ost d is-
ity can be attributed to improved immunosuppression and astrou s comp lication follow ing orthotop ic liver transplan-
advances in the diagnosis and management of complications. tation (OLT). Prim ary nonfu nction is d iagnosed by the
p resence of p rofou nd coagu lop athy, m etabolic acid osis,
■ COMPLICATIONS DURING DECEASED and hep atic transam inase valu es that are 3,000 U/ m L.
The etiology of prim ary nonfu nction is thou ght to be pri-
DONOR ORGAN PROCUREMENT
m arily p reservation inju ry, althou gh recip ient factors are
The liver transp lant p roced u re tru ly begins w ith the d onor im p ortant as w ell (9–11). Patients rap id ly becom e exceed -
organ. Desp ite the recent d evelop m ent of living d onor ingly ill w ith p rogressive renal, p u lm onary, neu rologic,
liver transp lantation, the vast m ajority of liver grafts in the and card iac failu re. Su rvival beyond the fifth p ostop erative
United States continu e to d erive from d eceased d onors. d ay is u ncom m on, and the only available therapy is
Com p lications that occu r d u ring p rocu rem ent of the liver retransp lantation. An effective m ethod of tem porary
graft from d eceased d onors inclu d e intraop erative card iac hep atic su p p ort continu es to be elu sive d esp ite d ecad es of
arrest and inju ry to the p ortal vascu lar stru ctu res. Donors research (12). Initial rep orts su ggested that p rostagland in
w ho su ffer intraop erative card iac arrest can be consid ered E1 m ay im p rove im m ed iate liver fu nction (13). Later stu d -
to be sim ilar to controlled d onation follow ing card iac ies of p rostagland in E1 therap y failed to d emonstrate a
d eath (DCD) d onors. As su ch, card iac arrest of the d onor clinically significant d ecrease in the rate of p rim ary non-
shou ld not be consid ered a contraind ication to d onation fu nction (14). To d ate, no p harm acologic therap y aim ed at
(5). N ijkam p et al. (6) rep orted that alm ost one in three p reventing p rim ary nonfu nction has been show n to be
d onor livers had som e inju ry related to p rocu rem ent. effective in controlled stu d ies.
While m ost w ere m inor, 7% w ere clinically relevant and The best m eans of d ealing w ith p rim ary nonfu nction in
17% w ere vascu lar in natu re (6). Inju ry to the p ortal vascu - liver transp lantation is avoid ing its occu rrence. N u m erou s
lar stru ctu res shou ld not generally p reclu d e u se of a d onor factors have been associated w ith p rim ary nonfu nction
graft for transp lantation given the m u ltip le op tions that inclu d ing steatosis of the liver graft, old er d onor age, pro-
longed cold ischem ia, DCD d onors, sp lit livers, need for
p ortal vein reconstru ction, d onor hyp ernatrem ia, and
Shawn J. Pelletier: University of Michigan H ealth System , transp lantation of high-risk recip ients (9,15–22). Desp ite
1500 East Med ical Center, Ann Arbor, MI 48109-5300 intensive scru tiny, objective variables fail to p rovid e strong
627
pred ictive valu e abou t w hether a d onor liver w ill function ■ INCISIONAL COMPLICATIONS
in the recip ient. In fact, the factor w ith the highest p red ic-
tive valu e has been the su bjective im p ression of the su r- Com p ared w ith other solid organ transp lant p roced u res,
geon w ho rem oved the graft from the d onor (23). liver transp lantation has one of the highest rates of su rgical
At p resent, p atients in the United States w ith prim ary site infection, d evelop ing in 10% to 38% of p atients (38–42).
nonfu nction are eligible to be re-listed as United N etw ork Liver recip ients that d evelop su rgical site infections have
for Organ Sharing (UN OS) Status 1A. This em ergency been found to have alm ost a three-fold increased risk for
transp lant statu s is reserved for p atients w ho received a graft loss or d eath (40). Pred isp osing factors inclu d e poor
transp lanted liver w ithin 7 d ays w ith an aspartate transam - w ound healing d ue to corticosteroid therapy, m alnu trition,
inase (AST) 3,000 along w ith either coagulopathy (IN R a high incid ence of w ou nd hem atom as second ary to
2.5) or an acid osis (d efined as having an arterial p H throm bocytop enia and coagu lop athy, attenu ated m u scula-
7.30, venou s p H 7.25, or lactate 4 m m ol/ L) or if the tu re d u e to ascites and cachexia, u se of Rou x-en-Y biliary
recipient is anhep atic (24). One-year patient su rvival fol- reconstru ction, sm all graft to recip ient m ass ratio, obesity,
low ing retransp lant for prim ary nonfunction has been and prolonged operative times (40,43). Although corticos-
reported at 66% and is not u nlike su rvival rates for retrans- teroid s are currently being greatly reduced, rapidly weaned ,
plantation for other ind ications (25). or eliminated from immunosuppressive regimens altogether,
Statu s 1A p atients receive regional priority over less ill it is likely that incisional hernias will remain a significant
patients. Desp ite this ad vantage, som e patients d eteriorate problem following this procedure. Newer immunosuppres-
d u ring the w aiting process. Total hepatectom y w ith tem po- sive agents, such as everolimus and sirolimus, that pro-
rary p ortacaval shu nt has been ad vocated as a p ossible foundly inhibit smooth muscle cellular proliferation have
means of avoid ing the ad verse effects associated w ith the been reported to increase the incidence of incisional compli-
effluent from the nonviable liver graft (26). There is insu ffi- cations if used perioperatively in liver transplant recipients
cient experience w ith this techniqu e to evaluate w hether it (44–46) but remains controversial (47).
offers a su rvival benefit. Incisional hernia rep air shou ld be d eferred u ntil the
p atient has stable graft function and has been w ithd raw n
from corticosteroid s or is taking a stable, low d ose. Repair
■ GRAFT REJ ECTION of large hernias of the bilateral su bcostal incision often
Liver transp lantation w as revolu tionized in the early entails the u se of a large p iece of m esh. Investigators report
1980s by the introd u ction of cyclosp orine and refined in success u sing laparoscopic techniqu es to repair incisional
the 1990s by the availability of tacrolim u s (27). Trip le hernias follow ing liver transp lantation (48,49).
im m u nosu p p ression therap y, inclu d ing a calcineu rin Abd ominal w all closu re follow ing liver transp lantation
inhibitor, m ycop henolate, and p red nisone, has been m ay not alw ays be p ossible d u e to a large liver allograft or
d em onstrated to have low er rejection rates w hen com - bow el ed em a from prolonged clam ping of the portal vein
p ared w ith d u al therap y (28). Desp ite this su ccess, acu te or m assive resu scitation if excess bleed ing w as encoun-
rejection rem ains relatively com m on follow ing liver tered . In this setting, abd om inal closu re may lead to unac-
transp lantation, w ith an incid ence betw een 7% and 60% cep table intrathoracic or abd om inal p ressu re. Acu te renal
(29–31). The m ajority of acu te cellu lar rejection ep isod es failu re is associated w ith excessive increases in intraab-
occu r early, u su ally w ithin 6 w eeks p ost-transp lantation. d om inal p ressu re p ostop eratively (50). This observation
Early ep isod es u su ally resolve w ith antirejection treat- suggests that som e instances of acu te renal failu re m ay be
m ent (29). Acu te rejection follow ing liver transp lantation avoid ed by recognition of intraabd om inal hyp ertension,
m ay be d ifficu lt to d iagnose d efinitively becau se recu rrent d efined as 25 m m H g (51), and treatment by reexplo-
d isease su ch as h ep atitis C viru s in fection (H CV) m ay ration and closu re of the incision w ith p rosthetic or biolog-
h ave sim ilar clin ical sign s an d am bigu ou s histop athol- ical m aterial if necessary (52). This ap p roach has been
ogy (32). Assays to evalu ate im m u ne fu nction (33) to aid in su ccessfu l w ith trau m a p atients, w here the abd om inal
the d iagnosis of acu te rejection are available bu t their u til- comp artm ent synd rom e has becom e a w id ely recognized
ity has yet to be valid ated in rand om ized clinical trials. p henom enon (53).
Unlike kid ney transplantation, the sharing of hu m an Fasciitis m ay lead to d ehiscence and an op en abd om en.
leukocyte antigens (H LAs) d oes not appear to d ecrease N u m erou s techniqu es have been d escribed for tem p orary
rejection rates (34). Also, u nlike kid ney transplantation, the w ou nd closu re in liver transp lant recip ients (54–56).
occu rrence of an ep isod e of acu te rejection in the first year Recently, the u se of biological m esh has been d escribed and
is not associated w ith w orsened long-term outcom e (35). can allow early closu re w ith avoid ance of abd om inal com -
Even late rejection d oes not carry an ad verse prognosis as p artm ent synd rom e (57). Figu re 48.1 d ep icts a liver recipi-
long as rejection is d etected and treated (36). Chronic ent w ho d evelop ed fasciitis and w as closed w ith hu m an
hepatic graft rejection, a rare phenom enon, m anifests as acellu lar d erm al m atrix after extensive fascial d ebrid e-
d u ctop enia, or the “vanishing bile d u ct synd rom e” (37). m ent. Use of the nonvascu larized fascia from d eceased
Once d u ctop enic rejection m anifests, the only effective d onor rectu s m u scle has also been d escribed w ith a low
treatm ent to d ate has been retransp lantation. incid ence of p ostop erative hernia (58).
Chapter 48 • Complications of Liver Transplantation 629
reconstruction w hen com pared w ith a bicaval technique

w ith (50%) or w ithou t (39%) venovenou s byp ass (60). The
sid e-to-sid e caval anastom osis (61) has also been su ggested
to resu lt in im proved inferior vena caval flow w ith partial
clam p ing (62) and to p otentially fu rther d ecrease the risk
for p ostop erative renal insu fficiency. For 500 patients
u nd ergoing liver transp lant u tilizing a cavocavostom y, the
incid ence of renal failu re w as rep orted at 6.2% (63).
Postoperative im m unosu ppression m ay also have an
effect on early renal fu nction. Cyclosp orine has been
d em onstrated to d ecrease renal blood flow and low er
glom eru lar filtration rates acu tely by u p to 43% (64). Inter-
leu kin (IL)-2 recep tor inhibitor (65–68) or antithym ocyte
globu lin (69–71) ind u ction m ay im p rove p ostoperative
renal fu nction by safely allow ing a d elay in starting a cal-
cineu rin inhibitor as w ell as a d ecreased d osage p ost-
FIGURE 48.1. Closure of an abdominal liver transplant incision with human transplantation.
acellular dermal matrix (AlloDerm®) after extensive fascial debridement for Chronic renal failu re is also a significant p roblem long
fasciitis complicating a wound infection. term , affectin g 18% an d 27% of liver recip ien ts at 5 an d
10 years p ost-transp lantation, resp ectively (72–74). Chronic
renal failu re has been associated w ith a 4.6-fold increased
■ RENAL FAILURE
risk of m ortality for nonrenal solid organ transplant recipi-
Renal failu re m ay occu r either acutely or chronically fol- ents (74). The u se of nep hrotoxic im mu nosu ppressive
low ing the p roced u re. Acu te renal failure is u sually d u e to agents, su ch as tacrolim u s and cyclosp orine, that ind uce
acu te tu bu lar necrosis. This comp lication is m ost often the p rogressive loss of renal fu nction is assu m ed to be the
resu lt of p oor renal p erfu sion d u ring the op eration d u e to p rim ary cau se of m ost renal insu fficiency in this setting.
intraop erative blood loss, clam ping of the suprarenal vena N ep h rotoxicity associated w ith ch ron ic calcineu rin
cava, or insu fficient replacem ent of flu id losses d u ring the inhibitor therap y may be p artially abrogated by institution
proced u re. Liver transp lant p atients are pred isp osed to the of m ycop henolate, sirolim u s, or everolim u s therapy and
d evelopm ent of acute tubular necrosis becau se of the phys- w ithd raw ing or low ering the d osage of the calcineu rin
iologic d erangem ents associated w ith cirrhotic liver d is- inhibitor w ithou t increasing the risk of either acu te or
ease. These inclu d e d ecreased blood pressu re, increased chronic graft rejection (75–78). Im p rovem ent in renal fu nc-
card iac ou tp u t, and d ecreased peripheral vascu lar resist- tion appears to be related to the d u ration of d ysfu nction.
ance. These hem od ynamic d istu rbances are believed to be Withd raw al of calcineu rin inhibitors after renal insu ffi-
cau sed by peripheral shunting of blood d ue to vasoactive ciency has reached an ad vanced stage is not associated w ith
su bstances that are im p rop erly m etabolized in the liver. the same d egree of improvement in renal function (79–81).
Together, these factors m ean that patients w ith ad vanced H ow ever, attempts at avoid ing calcineurin inhibitors alto-
chronic liver d isease are u niversally prerenal before the gether have been d isappointing d u e to an increase in early
operation begins. In ad d ition, many liver transp lant acu te rejection (82).
patients have p reexisting renal insu fficiency d ue to hep a- Interestingly, p atients w ho are treated w ith com bined
torenal synd rom e at the tim e of transp lantation. liver/ kid ney transplantation for chronic liver d isease asso-
Cu rrent liver allocation is based on the Mod el for End - ciated w ith ren al failu re have few er ep isod es of graft
stage Liver Disease (MELD) score in w hich an elevated rejection com p ared w ith recip ien ts of the con tralateral
seru m creatinine or a requ irem ent for d ialysis lead s to a grafts from the sam e d onor w h o received only the kid n ey
higher MELD score, increasing the likelihood for receiving grafts or com bined kid ney/ p an creas graft (83). This p h e-
a liver offer. Liver cand id ates requiring renal rep lacement n om en on is believed to be d u e to th e im m u nological
therap y for acu te renal failu re have been id entified to have ad vantage conferred by the liver graft on the kid ney
a w aiting list m ortality of u p to 65% and have p osttrans- grafts. The basis for this ap p arent im m u nological p henom -
plant 1-year m ortality alm ost three tim es higher (30% vs. enon is not und erstood .
9.7%) w hen comp ared w ith recipients not requiring renal
rep lacem ent therapy (59). Consid eration should be given
to com bined liver kid ney transp lantation for ap p rop riate
■ RECURRENT DISEASE
cand id ates. Recu rrence of the prim ary etiology for liver failure has
The influ ence of su rgical techniqu e on p ostop erative becom e an increasingly recognized long-term com plication
renal failu re rem ains controversial. Cabezuelo et al. of liver transp lantation. H ep atitis C viru s infection, now
rep orted a d ecreased incid ence of p ostop erative renal fail- the lead ing cau se of cirrhosis in the United States, recu rs
ure w ith u se of the piggyback techniqu e (18%) for caval in the vast m ajority of cases and lead s to cirrhosis w ithin
5 years in 25% of liver recipients (84). The incid ence of ■ GRAFT VERSUS HOST DISEASE
severe, early recu rrence of hepatitis C follow ing liver trans-
plantation ap p ears to be increasing, perhaps d ue to the Graft versu s host d isease (GVH D) occu rs w hen passenger
increased u se of old er liver d onors (85). While retransplan- lym p hocytes from the d onor that are w ithin the graft are
tation for graft loss related to hepatitis C recurrence remains transferred to an im m u nosu p p ressed host. The transferred
an option, retransplantation of liver recipients w ith H CV cells colonize the recip ient and recognize recip ient antigens
has been d em onstrated to have a significantly d ecreased 1- as foreign. Typ ically, the skin, intestines, and bone m arrow
year survival w hen compared w ith those retransplanted for are involved . Since the liver itself is not foreign relative to
other ind ications (2,86). the lym p hocytes, it is not involved . Desp ite the large nu m -
The p ossibility of recu rrent alcoholism has been a con- ber of d onor lym phocytes that are present in a liver graft,
cern for liver transplant surgeons since the inception of the GVH D is a very uncom m on problem follow ing liver trans-
proced u re. Fortu nately, the incid ence of recu rrent alcohol p lantation, w ith an incid ence of 1% (98). This low inci-
use in p atients receiving liver transplant for alcohol- d ence is p robably becau se d onor lym p hocytes are u su ally
ind uced cirrhosis is low, at approxim ately 15% (87). The very im m u nogenic and are p rom p tly d estroyed by the
incid ence of serious liver d amage d ue to recu rrent alcohol recip ient im m u ne system . The incid ence of GVH D is
use is even low er. Given that recid ivism rates follow ing higher w hen the d onor is both hap loid entical to the recip i-
conventional alcohol rehabilitation are generally 50%, it ent and also hom ozygou s at several H LA alleles. In this sit-
ap p ears that liver transp lantation is tru ly the “u ltim ate u ation, the recip ient’s im m u ne system d oes not recognize
eye-op ening exp erience.” the d onor lymp hocytes as foreign. Diagnosis is usually
For many years, it w as believed that autoim m une d is- m ad e by tissu e biop sy of the affected organ and confirm ed
eases d id not recur becau se of the im m unosu ppression by the find ing of circu lating d onor lym phocytes u sing flow
used to su p p ress graft rejection. H ow ever, carefu l follow - cytom etry. Treatm ent of GVH D consists of intensified
up of large cohorts of liver recip ients has d em onstrated im m u nosu p p ression. Antitu mor necrosis factor alp ha ther-
that au toim m u ne d iseases d o recu r in som e p atients. Pri- ap y has been w id ely u sed for the treatm ent of steroid -
mary biliary cirrhosis, p rim ary sclerosing cholangitis, and resistant acute GVH D in the hem atopoietic stem cell
au toim m u ne hep atitis each recur in 15% to 20% of p atients transplant setting and etanercept w as recently reported to
w ithin 5 years of the transplant (88–90). It is unclear be successful in a liver transplant recipient w ith GVH D
w hether m aintenance im m u nosu p p ression can be m anip u - (99). Desp ite therap y, m ortality is high (80%), w ith m ost
lated in su ch a w ay as to m inim ize recu rrent autoimm u ne p atients d ying of infection (100).
d isease. This possibility seems unlikely given that immuno-
suppression d oes not play a role in forestalling the d evelop-
ment of cirrhosis in these cond itions—w ith the possible
■ INFECTION
exception of autoim m une hep atitis. Since liver transplantation requ ires suppression of norm al
It is cu rrently u nclear w hether cryptogenic cirrhosis, an im m u nological resp onses, infection is an u navoid able com -
ind ication for transplantation in approxim ately one-sixth p lication, affecting as m any as 83% of liver transplant
of liver transp lant cand id ates, recu rs. Althou gh chronic recipients w ith the m ajority of severe infections occu rring
inflam m ation is com m only seen on post-transplant biop- w ithin the first 2 m onths p ost-transp lantation (101–103).
sies, the incid ence of graft failu re is low (91). Becau se of im mu nosu p p ression, the signs and sym ptom s
H ep atocellu lar carcinom a is the fifth m ost com m on of severe, p ost-transp lant infection m ay or m ay not be sub-
cancer w orld w id e (92) w ith the nu m ber of H CC cand i- tle or abated (104) and a high level of su sp icion m u st be
d ates on the liver transp lant w aiting list increased by m aintained for early d iagnosis and im p roved ou tcom es.
108% from 2002 to 2008 (2). Transp lant of ap p rop riate can- Infections that occur d uring the initial transplant ad m is-
d id ates w ith stage II or earlier H CC sim u ltaneou sly treats sion are associated w ith a m ortality rate of 30% com p ared
the m alignancy and u nd erlying liver d isease and can w ith 8% for those occu rring in su bsequ ent ad m issions
resu lt in a 4-year p atient su rvival rate of 75% and a recu r- (102).
rence-free su rvival of 83% (93). If recu rrent H CC is id enti- In ad d ition to the u su al bacterial infections that are
fied on p ost-transp lant surveillance, stand ard treatm ent associated w ith p ostop erative p atients, liver transplant
includ es minim ization of im m u nosupp ression. Becau se of recipients are also p rone to viral and fu ngal infections.
their antineop lastic effects, the use of sirolim u s (94) or Acu te rejection, obesity, and p rolonged hosp italization are
everolim u s (95) has been reported w ith variable su ccess. clear risk factors for clinically im p ortant infections
Su rgical resection m ay be p ossible for isolated areas of (105,106). Biliary com p lications also d ram atically increase
recu rrence and has been associated w ith reasonable long- the risk of infection. Ap p roxim ately 20% of late graft loss
term su rvival (96). Recent reports have suggested a p ossi- (after 1 year) in p ed iatric liver recip ients is attribu table to
ble benefit of sorafenib (97). Overall, m ean survival rates infection (107). Cytom egaloviru s (CMV) infection, once a
vary betw een 5 m onths for recipients w ith unresectable com mon p roblem , has becom e m u ch less com m on d u e to
recu rrent d isease and 65 m onths for those u nd ergoing the routine use of prophylactic oral ganciclovir and valgan-
resection (96). ciclovir.
Fungal infections m ay be m inim ized by prophylaxis fou nd in OLT recip ients. Sm oking cessation at least 2 years
w ith top ical m ycostatin or oral flu conazole or itraconazole before OLT d ecreased the risk (116).
(108). N ew er agents m ay offer im proved efficacy against While su ccessfu l throm bectom y and throm bolysis has
asp ergillosis and other fu ngi, rare but d ead ly op portu nistic been rep orted u sing an end ovascu lar ap p roach (117–119),
post-transp lant infections (109). there is lim ited experience and few prospective stud ies
rep orted in the literatu re w ith this ap p roach. Urgent intra-
op erative throm bectom y w ith intraop erative throm bolysis
■ VASCULAR COMPLICATIONS
and arterial reconstru ction can restore arterial flow in u p to
Vascu lar complications in general occur at a rate of app rox- 88% of recip ients w ith early H AT w ith a 17-m onth graft
im ately 10% of all liver transplant recipients and are a fre- su rvival of 65% (120). In the p ed iatric p op u lation, im m ed i-
qu ent cau se of early graft loss. Diagnosis is u su ally ate su rgical throm bectom y for H AT m ay lead to long-term
suggested by graft d ysfunction and confirmed by Doppler graft salvage in approxim ately one of three recipients w hile
exam ination of the hepatic vasculature. Extensive ascites, others m ay lose their graft to biliary com p lications related
hem atom a, bod y habitu s, and bow el gas can m ake the inter- to ischem ia. In contrast, im m ed iate retransp lantation m ay
pretation of Doppler stu d ies d ifficult in some p atients (110). have an im p roved 5-year p atient su rvival (approxim ately
Many centers ad vocate contrast computed tomography 70%) bu t requ ires the u tilization of a second d onor organ.
(CT), and it can be an alternative noninvasive technique. Because of the d onor organ shortage, attempts at throm bec-
Magnetic resonance evaluation is the choice if patients have tom y shou ld be m ad e w hen possible.
allergic reactions to contrast or impaired renal fu nction d u e
to the use of iod inated contrast m aterial (111). Magnetic res-
onance scanning may also be useful for confirm ation of
■ HEPATIC ARTERY STENOSIS
ultrasou nd stu d ies and for the evalu ation of hepatic out- In some instances, hepatic artery stenosis is diagnosed
flow p roblem s. Selective angiography remains the gold because of an elevation of hepatic enzymes, because of new
stand ard for d iagnosing vascular com plications. onset biliary complications, or on the basis of a Doppler
stud y obtained for som e other, unrelated reason. Although
Doppler ultrasonography may suggest this problem, confir-
■ HEPATIC ARTERY THROMBOSIS
mation w ith angiography is usually required (Fig. 48.2A).
H ep atic artery throm bosis (H AT), the m ost com m on vascu - Most stenoses occur at either the anastomotic site or because
lar com p lication of OLT, has an incid ence of 4% to 12% in of clamp injury on the native vessel. When d etected early in
ad u lt p atients and u p to 40% in child ren, w ith a m ortality the postoperative period, abd ominal exploration w ith take-
rate of as high as 50% to 60% (112). The clinical presentation d ow n and thrombectomy may be an effective therapeutic
of H AT varies from m ild transam inase elevation d u e to option (121). In some instances w hen recipient inflow is the
ischem ic changes in the liver parenchym a to d elayed bile problem, the use of ad ditional donor arterial graft is neces-
leak, bile d u ct strictu res, and relap sing bacterem ia and sep - sary to reestablish arterial flow. In cases of late arterial steno-
sis. Acu te throm bosis in the first w eek follow ing a liver sis, selective angiography and balloon angioplasty may be
transp lant is associated w ith biliary necrosis and graft fail- successful (Fig. 48.2B) (122). When the d onor arterial system
ure and invariably requ ires retransplantation if throm bec- is d amaged and after a revision there is absence of flow,
tom y cannot be p erform ed (113). In contrast, late H AT has a retransplantation is necessary.
variable clinical cou rse w ith one-third of p atients not
requ iring intervention (114).
Mu ltip le risk factors for H AT have been id entified .
■ HEPATIC ARTERY PSEUDOANEURYSM
Technical factors inclu d e a d ifference in the caliber of d onor Hepatic artery pseudoaneurysm is an uncommon but life-
and recip ient arteries, preexisting lesions such as hep atic threatening complication after OLT. It occurs more com-
artery d issection in the d onor or recip ient and celiac steno- monly in the presence of infected biloma or after using
sis. A recip ient to d onor w eight ratio of 1.25 is a clear risk arterial graft reconstruction. H epatic artery pseud oa-
factor. The need for reconstru ctive arteriop lasty in the p res- neurysms can rupture intraperitoneally and lead to massive
ence of nonstand ard d onor anatom y, present in as m any as hemorrhage. The possibility of a mycotic pseudoaneurysm
50% of d onor livers, is know n to pred ispose to H AT. N on- should be considered (123). Treatment options include surgi-
technical factors also p red isp ose to hep atic artery p rob- cal resection and reconstruction using homograft, emboliza-
lem s, m ost likely becau se they are associated w ith graft tion, or exclusion with stent placement (124).
ed em a and p oor flow. N ontechnical factors inclu d e p ro-
longed cold ischem ia tim e, ABO-type incom p atibility,
biop sy-p roven rejection w ithin the first w eek post-trans-
PORTAL VEIN THROMBOSIS OR STENOSIS
plant, d onor p ositive/ recip ient negative CMV statu s, and Portal vein com plications follow ing OLT are relatively
the G20210 A prothrom bin polym orp hism (112,115). u ncommon, occurring at a rate of only 1% to 3% (125). Por-
Recently, a strong association betw een cigarette sm oking tal venous com plications are u su ally the result of a technical
and increased incid ence of arterial throm bosis has been surgical problem , su ch as size d iscrep ancy, m isalignm ent,
A B
FIGURE 48.2. A: Selective hepatic arteriogram demonstrating anastomotic narrowing of the hepatic artery. B: Arteriogram following
balloon angioplasty showing resolution of the narrowing.
or purse-stringing cau sing turbulent flow. A higher inci- cu m stance is p articu larly p roblem atic w hen the d onor is
d ence of p ortal vein p roblem s is seen in patients w ho have sm all relative to the recip ient. IVC throm bosis can be
had p revious portal vein op erations or prior throm bosis of cau sed by a hyp ercoagu lable state or by technical errors,
the p ortal system and are at an increased risk for p ostsu ch as inclu d ing the back w all of the anastom osis w hen
transp lant m ortality (126). Patients w ith portal vein throm - su tu ring the front w all. H ep atic ou tflow p roblem s u su -
bosis or stenosis typ ically p resent w ith com plications of ally p resent w ith low er extrem ity ed em a or severe ascites,
portal hyp ertension, inclu d ing variceal bleed ing and or both .
ascites. The incid ence of ou tflow p roblem s ap p ears to be
Dop p ler u ltrasou nd exam ination is u su ally the first related to su rgical techniqu e. The trad itional bicaval anas-
d iagnostic tool, bu t it is in ad equ ate to assess p ortal p res- tom otic techniqu e involves resection of the intrahep atic
su re grad ients across a strictu re or focal narrow ing. Per- p ortion of the recip ient vena cava and sep arate su p rahep -
cu taneou s transhep atic d irect p ortograp hy allow s the atic and infrahep atic anastom osis of the d onor vena cava
m easu rem ent of p ressu res across a stenotic area, w ith to the recip ient (Fig. 48.5A). The incid ence of caval
valu es of 5 m m H g being consid ered significant. Percu - obstru ction u sing this techniqu e is 1% to 2% (131). The
taneou s translu m inal angiop lasty w ith or w ithou t stent “p iggyback techniqu e,” involving p reservation of the
p lacem en t m ay also be a good choice for th is p articu lar recip ient cava, oversew ing of the d onor infrahep atic cava,
p roblem (Fig. 48.3) (127–129). In cases w here there is a and end -to-sid e anastom osis betw een the d onor and recip -
recalcitrant strictu re, su rgical intervention, inclu d ing ient su p rahep atic cava, has been ad vocated as a m eans of
throm bectom y, p lacem ent of a venou s ju m p graft, u se of obviating venovenou s byp ass (Fig. 48.5B) (132,133). The
the left renal vein (130), or creation of a p orto-system ic incid ence of caval com p lications u sing the p iggyback tech-
shu nt, m ay be necessary. In very severe cases in w hich niqu e ap p ears to be higher, at ap p roxim ately 4% (134).
frank hep atic d ecom p ensation occu rs, retran sp lan tation Ou tflow stenosis ap p ears to be m ore com m on if the com -
m ay be the only op tion. bined orifice of tw o, rather than three, hep atic veins is
u sed for the anastom otic site on the recip ient (134). More
recently, a sid e-to-sid e cavocavostom y, w here the recip ient
■ COMPLICATIONS OF THE IVC ANASTOMOSIS
vena cava is p artially clam p ed in a longitu d inal fashion,
Com p lications arising from the vena cava anastom osis, the su p ra- and infrahep atic d onor IVC is stap led or over-
either stenosis or occlu sion, accou nt for a sm all p ercent- sew n, and a venotom y on the p osterior asp ect of the d onor
age of all com p lication s. Vena cava p roblem s that take vena cava is su tu red to a longitu d inal venotom y on the
p lace in traop eratively relate to venou s tears in the recip i- anterior asp ect of the recip ient IVC, has been d escribed
ent’s cava, w hich m ay lead to catastrop hic hem orrhage or (Fig. 48.6) (61–63). The sid e-to-sid e cavocavostom y appears
air em bolism . Rap id sternotom y and con trol of th e to have a low er rate of IVC com p lications sim ilar to the
intrap ericard ial p ortion of the IVC m ay be life-saving in bicaval techniqu e w ithou t the requ irem ent of com p lete
this situ ation. Post-transp lant com p lications can relate to caval occlu sion d u ring anastom osis.
size d iscrep ancy betw een the d onor and recip ient, allow - In m any cases, hep atic vein or su p rahep atic caval steno-
ing for rotation of the graft and kinking at the level of the sis can be su ccessfu lly treated noninvasively w ith the u se
su p rahep atic vena cava anastom osis (Fig. 48.4). This cir- of balloon angiop lasty, or stenting, or both (135,136).
A
B
FIGURE 48.3. A: Transhepatic portal venogram showing narrowing of the portal vein
anastomosis. B: Balloon angioplasty of the portal vein at the area of narrowing. C: Portal
C
venogram following angioplasty showing resolution of the anastomotic narrowing.
■ BILIARY COMPLICATIONS
Biliary com p lications follow ing liver transp lantation con-
tinu e to cau se su bstantial m orbid ity in both the early and
late p eriop erative p eriod s (137). In general, biliary com p li-
cations can be d ivid ed into (a) anastom otic leaks, (b) anas-
tom otic strictu res, and (c) intrahep atic biliary strictu res.
Both anastom otic leaks and strictu res are often am enable
to end obiliary, p ercu taneou s, or su rgical therap y w hile
intrahep atic biliary strictu res tend to be m ore d iffu se and
p rogressive, p ossibly lead ing to graft loss. In sp ite of better
u nd erstand ing of the biliary blood su p p ly, im p roved su r-
gical techniqu e, and the u se of absorbable su tu re m aterial,
the rep orted biliary com p lication rate varies from 10% to
41% (137,138). The p athogenesis of biliary com p lications is
m u ltifactorial. The single m ost im p ortant factor ap p ears to
be p oor or absent arterial flow. The transected d onor bile
FIGURE 48.4. Venogram of the IVC performed 2 weeks after liver trans- d u ct is totally d ep end ent on arterial flow from the liver
plantation of a relatively small allograft into a larger recipient using a piggy- graft. Factors that have been associated w ith biliary p rob-
back technique. The suprahepatic vena cava is stenotic at the junction of the
lem s inclu d e p rolonged cold and w arm ischem ia tim e,
right atrium, likely as a result of rotation of the graft and kinking of the vena
cava. This stenosis was successfully treated with venoplasty and stenting of sp hincter of Od d i d ysfu nction, CMV infection, vascu lar
the IVC and right hepatic vein. rejection, and ABO incom p atibility. Recip ients w ith a
FIGURE 48.5. A: Liver transplant

using bicaval technique showing
Diaphragm
the relationship between the donor
liver, the donor cava, and the recipi-
ent cava. B: Liver transplant using
the piggyback technique, showing
er
ch
the relationship between the donor Fis
liver, the donor cava, and the recipi- HR
ent cava.
Donor
inferior
vena cava
Donor
liver
Diaphragm
er
ch
s
R Fi
H
Recipient inferior
vena cava
Donor inferior
Donor vena cava
liver
d iagnosis of p rim ary sclerosing cholangitis have a higher remain abnorm ally elevated in the periop erative period or
rate of biliary com p lications. w hen these valu es rise after a p eriod of d ecline. Biliary leak
Early d iagnosis and treatm ent of biliary com p lications or strictu re is su ggested by the d evelop m ent of abd om inal
is param ou nt. Diagnostic proced u res shou ld take p lace p ain, nau sea, or p ersistent fever and by the d evelopm ent of
urgently w hen biliru bin or alkaline p hosphatase levels ascites w ith a biliru bin level greater than seru m or the pres-
ence of frank bile in a su rgically p laced d rain. Whenever a
biliary comp lication is id entified , it is im p ortant to ru le out
Donor liver hep atic arterial throm bosis w ith a Dop p ler u ltrasou nd
exam ination.
Tw o general techniqu es, namely, d u ct to d uct and Roux-
Donor IVC en-Y hepatico-jejunostomy, are used for biliary anastomosis
in liver transplantation. In ad d ition, a T-tube or other exter-
nal biliary stent (139) may be placed , allow ing for monitor-
Recipient IVC ing of bile production and for contrast injection for diagnostic
purposes. When a T-tube or external biliary stent is in place
and a biliary complication is suspected, a cholangiogram
through the stent is the first d iagnostic test that should be
FIGURE 48.6. Liver transplant using a side-to-side cavocavostomy tech-
nique. The relationship between the donor liver, inferior vena cava (IVC), and performed. Use of an internal biliary stent has been demon-
recipient IVC is shown. strated to d ecrease the risk of biliary com plications (137).
initial studies show a large defect and in cases where the leak
is not controlled through percutaneous measures, operative
repair using a Roux-en-Y hepatico-jejunostomy is indicated.
Similarly, anastomotic strictures can generally be managed
nonoperatively using ERCP or percutaneous cholangioplasty
Anastamotic stricture (Fig. 48.7). When anastomotic strictures persist beyond two
attempts at balloon d ilatation and stent replacement, opera-
tive repair should be performed (140,141).
Late leaks, follow ing 1-month post-transplant, are associ-
ated with T-tube removal. The incidence of this problem is
35%, but episod es are usually short-lived and resolve after
a period of observation with antibiotic therapy. In some
instances, it may be ad visable to insert a small feed ing tube
or other drain through the previously formed tract to serve
as a drain until symptoms resolve. ERCP or percutaneous
transhepatic cholangiogram injection and ultrasound or CT-
FIGURE 48.7. Transhepatic cholangiogram showing severe stenosis of the guid ed placement of d rains is necessary in cases w here
bile duct at the duct to duct anastomosis that responded to balloon dilatation.
abdominal pain and/ or fluid collections persist. Surgical
intervention is only rarely necessary w hen a large d efect is
In the absence of an external stent, an ultrasound examina- id entified , w hich cannot be controlled noninvasively (142).
tion follow ed by end oscopic retrograd e cholangiopancre- Because of the increased rate of complications directly
atography (ERCP) is app ropriate. ERCP has the ad vantage related to the tube itself, T-tube placement is rarely utilized.
of being potentially both d iagnostic and therapeutic w hen Diffuse intrahepatic strictu res or intrahepatic cholan-
combined w ith sphincterotomy and the insertion of an giop athy is often related to d onor ischem ia, poor organ
internal stent. Percu taneou s transhepatic cholangiography p reservation, H AT, im m u nologic inju ry, or recurrent d is-
is a m ore invasive alternative, w hich is u su ally reserved for ease (prim ary sclerosing cholangitis) and can be refractory
cases w here ERCP is not possible, such as patients w ith to treatm ent, p rogressive, and lead to graft loss (143). The
Rou x-en-Y bile d uct reconstru ction. highest incid ence of intrahep atic cholangiop athy, ranging
The initial management of biliary complications can gen- from 10% (144) u p to 50% (145), occu rs follow ing the
erally be nonoperative. Management should includ e intralu- transp lantation of DCD livers (Fig. 48.8). Attem p ts at per-
minal and external drainage, antibiotic administration as cu taneou s d rainage can occasionally be su ccessful, bu t
indicated, and reevaluation at 4 to 6 weeks. In cases w here retransplantation is often required .
A B
FIGURE 48.8. A: Bilateral percutaneous cholangiogram 6 weeks after transplantation of a liver from a donation following cardiac
death (DCD) donor. Diffuse intrahepatic strictures and pruning of the intrahepatic biliary tree are noted. B: Abdominal CT scan of the same
DCD liver recipient demonstrating bilateral, diffuse bile lakes.
■ COMPLICATIONS OF LIVING DONOR require a right lobe graft to supply sufficient hepatic mass
for the recipient. The mass of the d onor graft should be at
LIVER TRANSPLANTATION
least 0.8% of the recipient’s body mass to support the recipi-
Since its inception in 1989, living donor liver transplantation ent until a normal hepatic mass can regenerate, a process
has gradually become a standard treatment for patients with that takes several w eeks. Grafts that are 1% of recipient
liver failure. Originally d eveloped to overcome the inad e- body weight exhibit risk of post-transplant graft dysfunction
quate number of organ donors for child ren, the technique has (161). Graft d ysfunction is m anifested by prolongation of
more recently been applied to adult liver transplantation for prothrombin time, necessitating continued infusions of fresh
the same reason (142). Several complications are relatively frozen plasma and persistent elevation of total bilirubin that
unique to living donor transplantation. It has been said that may require retransplantation in some cases. Morbidity and
living donor transplantation is the only surgical proced ure mortality d ue to septic complications are also more com-
that has a potential mortality of 200%, causing the death of mon. Recipient factors are also know n to play a role, as the
both the donor and the recipient. It is interesting to compare small-for-size synd rome is observed more commonly w hen
living d onor liver transplantation, which has only recently the recipient is extremely ill (162). One theory regarding the
been developed, to living donor kidney transplantation. In etiology of the graft d ysfunction in small-for-size syndrome
the 1950s, the first successful kidney transplants used living is that the hepatic dysfunction relates to “hyperperfusion” of
donors (identical tw ins) (146). Since that time, living d onor the graft w ith portal blood, w hich causes a compensatory
kidney transplantation has become increasingly accepted to d ecrease in hepatic arterial flow. Method s to attenuate graft
the point that living kidney donors now outnumber d ysfunction w ith small-for-size grafts by temporarily shunt-
deceased kid ney d onors. The mortality of donating a kidney ing portal blood away from the graft have been suggested
is approximately 0.03% (147). The long-term consequences of and are currently being evaluated (163).
donating a kidney appear to be minimal (148). In contrast, the Because of the complexity of the proced ure and the
risk of donating the right hepatic lobe is estimated at 0.2% to severity of illness of those w ith acute or chronic liver failure,
0.8% (149,150), lead ing some experts to question the develop- complications follow ing liver transplantation are antici-
ment of the practice of adult-to-adult donation (151). pated in nearly all recipients. Signs and symptoms of com-
In addition to ethical issues related to donor mortality, plications may be abated or d elayed and a high ind ex of
the morbid ity of the proced ure is significant, w ith 12% to suspicion must be maintained to aid in the early d iagnosis
67% of donors experiencing major complication (152–156). to lim it m orbid ity and m ortality. Continu ed ad vancem ents
The risk of d onor morbidity appears to be higher for right in periop erative p atient m anagem ent, im m u nosu pp ression,
lobe donors than for left lateral segment donors. In right lobe and surgical techniqu es have im proved ou tcomes so that
donors, biliary complications occur in approximately 15% of 90% 1-year patient su rvival has become the norm.
cases (157). Although most biliary problems can be treated
nonoperatively w ith ERCP or percutaneous d rainage, some
require operative repair. Although the donor liver regener-
■ REFERENCES
1. Roberts JP, Brow n RS Jr, Ed w ard s EB, et al. Liver and intestine trans-
ates, the long-term consequences of the d onor operation are plantation. Am J Transplant 2003;3(Su p p l 4):78–90.
unknown (158). 2. Thu lu vath PJ, Gu id inger MK, Fu ng JJ, et al. Liver transp lantation in
Biliary com p lications are p articu larly com m on follow - the United States, 1999–2008. Am J Transplant 2010;10:1003–1019.
3. Pru thi J, Med kiff KA, Esrason KT, et al. Analysis of cau ses of d eath in
ing living d onor liver transplantation, w ith an incid ence of liver transp lant recip ients w ho su rvived m ore than 3 years. Liver
betw een 16% and 38% (159). Biliary reconstru ction is u su - Transpl 2001;7:811–815.
ally perform ed in living d onor liver transplantation u sing 4. Rabkin JM, d e La Melena V, Orloff SL, et al. Late m ortality after ortho-
topic liver transplantation. Am J Surg 2001;181:475–479.
either Roux-en-Y hepatico-jeju nostom y or d u ct-to-d u ct 5. Moon JI, N ishid a S, Butt F, et al. Mu lti-organ p rocurem ent and success-
anastom osis. Dep end ing on the plane of transection, a sin- ful m ulti-center allocation using rapid en bloc technique from a con-
gle or d ou ble anastomosis m ay be necessary. The u se of trolled non-heart-beating d onor. Transplantation 2004;77:1476–1477.
6. N ijkam p DM, Slooff MJ, van d er H ilst CS, et al. Su rgical inju ries of
intrabiliary stenting is com m on practice. Most p rogram s postm ortem d onor livers: incid ence and im pact on outcom e after
evaluate the d uct anatomy at the tim e of abd om inal explo- ad u lt liver transp lantation. Liver Transpl 2006;12:1365–1370.
ration w ith either intraop erative cholangiograp hy or p robe 7. Gold stein RM, Secrest CL, Klintm alm GB, et al. Problem atic vascu lar
reconstruction in liver transp lantation. Part I. Arterial. Surgery
exploration throu gh the cystic d uct after cholecystectom y. 1990;107:540–543.
When the tw o d u cts are in close proxim ity, a d uctop lasty 8. N icolini D, d i Francesco F, Cau tero N , et al. Technical solu tions for
can be p erform ed , allow ing the creation of a single orifice venou s ou tflow reconstru ction in d am aged liver grafts d u ring p ro-
curem ent: case reports. Transplant Proc 2008;40:1941–1943.
and a larger anastom otic opening (160). 9. Strasberg SM, H ow ard TK, Molm enti EP, et al. Selecting the d onor
One of the major difficulties during the development of liver: risk factors for poor fu nction after orthotopic liver transplanta-
the living donor technique has been the choice of graft. For tion. Hepatology 1994;20:829–838.
10. Abt PL, Desai N M, Craw ford MD, et al. Su rvival follow ing liver trans-
ped iatric recipients the left lateral segment comprising seg- plantation from non-heart-beating d onors. Ann Surg 2004;239:87–92.
ments 2 and 3 has usually been selected . H ow ever, w hen the 11. Oh CK, Saw yer RG, Pelletier SJ, et al. In d ep en d en t p red ictors for
recipient is large ( 30 kg), it may be necessary to use an p rim ary n on -fu n ction after liver tran sp lan tation . Yonsei Med J
2004;45:1155–1161.
extend ed left graft that includes segment 1 (the caudate 12. Ad ham M. Extracorp oreal liver su p p ort: w aiting for the d ecid ing
lobe), or segment 4, or both. Ad ult recipients generally vote. ASAIO J 2003;49:621–632.
13. Takaya S, Doyle H , Tod o S, et al. Red u ction of p rim ary nonfunction 38. Gom ez R, H id algo M, Marqu es E, et al. Incid ence and p red isp osing
w ith p rostagland in E1 after clinical liver transp lantation. Transplant factors for incisional hernia in p atients w ith liver transp lantation. Her-
Proc 1995;27:1862–1867. nia 2001;5:172–176.
14. H enley KS, Lucey MR, N orm olle DP, et al. A d ou ble-blind , rand om - 39. Janssen H , Lange R, Erhard J, et al. Cau sative factors, su rgical treat-
ized , placebo-controlled trial of p rostagland in E1 in liver transplanta- m ent and ou tcom e of incisional hernia after liver transp lantation. Br J
tion. Hepatology 1995;21:366–372. Surg 2002;89:1049–1054.
15. Johnson SR, Alexop ou los S, Cu rry M, et al. Prim ary nonfunction 40. H ellinger WC, Crook JE, H eckm an MG, et al. Su rgical site infection
(PN F) in the MELD Era: an SRTR d atabase analysis. Am J Transplant after liver transplantation: risk factors and association w ith graft loss
2007;7:1003–1009. or d eath. Transplantation 2009;87:1387–1393.
16. Marsm an WA, Wiesner RH , Rod rigu ez L, et al. Use of fatty d onor 41. H ollenbeak CS, Alfrey EJ, Sou ba WW. The effect of su rgical site infec-
liver is associated w ith d im inished early patient and graft survival. tions on outcom es and resou rce utilization after liver transplantation.
Transplantation 1996;62:1246–1251. Surgery 2001;130:388–395.
17. Kim DY, Caud uro SP, Bohorqu ez H E, et al. Rou tine u se of livers from 42. Iinu m a Y, Send a K, Fu jihara N , et al. Su rgical site infection in living-
d eceased d onors old er than 70: is it ju stified ? Transpl Int 2005;18: d onor liver transp lant recip ients: a p rosp ective stu d y. Transplantation
73–77. 2004;78:704–709.
18. Bu squ ets J, Xiol X, Figu eras J, et al. The im p act of d onor age on liver 43. Saw yer RG, Pelletier SJ, Pru ett TL. Increased early morbid ity and m or-
transplantation: influ ence of d onor age on early liver fu nction and tality w ith acceptable long-term fu nction in severely obese patients
on subsequ ent p atient and graft su rvival. Transplantation 2001;71: und ergoing liver transplantation. Clin Transplant 1999;13: 126–130.
1765–1771. 44. Gu ilbeau JM. Delayed w ou nd healing w ith sirolim u s after liver trans-
19. Totsuka E, Dod son F, Urakam i A, et al. Influ ence of high d onor seru m plant. Ann Pharmacother 2002;36:1391–1395.
sod iu m levels on early p ostop erative graft fu nction in hu m an liver 45. Toso C, Meeberg GA, Bigam DL, et al. De novo sirolimus-based immuno-
transplantation: effect of correction of d onor hyp ernatrem ia. Liver suppression after liver transplantation for hepatocellular carcinoma:
Transpl Surg 1999;5:421–428. long-term outcomes and side effects. Transplantation 2007;83: 1162–1168.
20. Abt P, Craw ford M, Desai N , et al. Liver transp lantation from con- 46. Mehrabi A, Fonou ni H , Wente M, et al. Wou nd com p lications follow -
trolled non-heart-beating d onors: an increased incid ence of biliary ing kid ney and liver transp lantation. Clin Transplant 2006;20(Su p p l
com plications. Transplantation 2003;75:1659–1663. 17):97–110.
21. Foley DP, Fernand ez LA, Leverson G, et al. Donation after card iac 47. Molinari M, Berm an K, Meeberg G, et al. Mu lticentric ou tcom e analy-
d eath: the University of Wisconsin exp erience w ith liver transp lanta- sis of sirolim u s-based im m u nosu p p ression in 252 liver transp lant
tion. Ann Surg 2005;242:724–731. recip ients. Transpl Int 2010;23:155–168.
22. Sharm a R, Kashyap R, Jain A, et al. Su rgical com p lications follow ing 48. And reoni KA, Lightfoot H Jr, Gerber DA, et al. Lap aroscop ic inci-
liver transp lantation in p atients w ith p ortal vein throm bosis—a sin- sional hernia repair in liver transplant and other im m u nosuppressed
gle-center p ersp ective. J Gastrointest Surg 2010;14:520–527. patients. Am J Transplant 2002;2:349–354.
23. Zam ir GA, Markm ann JF, Abram s J, et al. The fate of liver grafts 49. Mekeel K, Mu lligan D, Red d y KS, et al. Lap aroscop ic incisional hernia
d eclined for su bjective reasons and transp lanted ou t of a local organ rep air after liver transp lantation. Liver Transpl 2007;13:1576–1581.
procu rem ent organization. Transplantation 2000;70:1149–1154. 50. Biancofiore G, Bind i ML, Rom anelli AM, et al. Postop erative intra-
24. H ealth Resources and Services Ad m inistration and Organ Procu re- abd om inal pressu re and renal function after liver transp lantation.
m ent and Transp lantation N etw ork. Policy 3.6 Organ Distribu tion: Arch Surg 2003;138:703–706.
Allocation of Livers. Vol. 2010. UN OS Liver Allocation Policy; 2010. 51. Kron IL, H arm an PK, N olan SP. The m easu rem ent of intra-abd om inal
http:/ / optn.transplant.hrsa.gov/ Policiesand Bylaw s2/ policies/ pd fs/ pressure as a criterion for abd om inal re-exploration. Ann Surg 1984;199:
policy_8.pd f. Accessed Janu ary 18, 2011. 28–30.
25. Uem u ra T, Rand all H B, Sanchez EQ, et al. Liver retransp lantation for 52. Biancofiore G, Bind i L, Rom anelli AM, et al. Renal failu re and abd om -
prim ary nonfu nction: analysis of a 20-year single-center exp erience. inal hypertension after liver transplantation: d eterm ination of critical
Liver Transpl 2007;13:227–233. intra-abd om inal pressu re. Liver Transpl 2002;8:1175–1181.
26. Old hafer KJ, Bornscheu er A, Fru hau f N R, et al. Rescu e hep atectom y 53. Ivatu ry RR, Su germ an H J, Peitzm an AB. Abd om inal com p artm ent
for initial graft non-fu nction after liver transp lantation. Transplanta- synd rom e: recognition and m anagem ent. Adv Surg 2001;35:251–269.
tion 1999;67:1024–1028. 54. Jones WT, Ratner I, Abraham ian G, et al. Use of a silastic silo for clo-
27. Calne RY. Im m u nosu p p ression in liver transp lantation. N Engl J Med sure of the abd om inal w all in a ped iatric patient receiving a cad averic
1994;331:1154–1155. sp lit liver. J Pediatr Surg 2003;38:E20–E22.
28. Wiesner RH , Steffen BJ, David KM, et al. Mycop henolate m ofetil u se is 55. Seam an DS, N ew ell KA, Pip er JB, et al. Use of p olytetraflu oroethylene
associated w ith d ecreased risk of late acu te rejection in ad ult liver patch for tem porary w ound closu re after ped iatric liver transp lanta-
transplant recipients. Am J Transplant 2006;6:1609–1616. tion. Transplantation 1996;62:1034–1036.
29. Dem etris AJ, Rup p ert K, Dvorchik I, et al. Real-tim e m onitoring of 56. Jafri MA, Tevar AD, Lu cia M, et al. Tem p orary silastic m esh closu re
acu te liver-allograft rejection u sing the Banff schem a. Transplantation for ad ult liver transp lantation: a safe alternative for the d ifficult
2002;74:1290–1296. abd om en. Liver Transpl 2007;13:258–265.
30. Jain A, Kashyap R, Dod son F, et al. A p rosp ective rand om ized trial of 57. Singh MK, Rocca JP, Rochon C, et al. Op en abd om en m anagem ent
tacrolim us and p red nisone versu s tacrolim u s, p red nisone and w ith hu m an acellu lar d erm al m atrix in liver transplant recipients.
m ycophenolate m ofetil in prim ary ad ult liver transp lantation: a sin- Transplant Proc 2008;40:3541–3544.
gle center report. Transplantation 2001;72:1091–1097. 58. Gond olesi G, Selvaggi G, Tzakis A, et al. Use of the abd om inal rectu s
31. Ram irez CB, Doria C, d i Francesco F, et al. Basilixim ab ind u ction in fascia as a nonvascu larized allograft for abd om inal w all closure after
ad u lt liver transp lant recip ients w ith 93% rejection-free p atient and liver, intestinal, and m u ltivisceral transp lantation. Transplantation
graft su rvival at 24 m onths. Transplant Proc 2006;38:3633–3635. 2009;87:1884–1888.
32. Burton JR Jr, Rosen H R. Acu te rejection in H CV-infected liver trans- 59. Wong LP, Blackley MP, And reoni KA, et al. Su rvival of liver transp lant
plant recipients: the great conu nd ru m . Liver Transpl 2006;12:S38–S47. cand id ates w ith acute renal failure receiving renal replacem ent ther-
33. Cabrera R, Ararat M, Sold evila-Pico C, et al. Using an im m u ne fu nc- ap y. Kidney Int 2005;68:362–370.
tional assay to d ifferentiate acu te cellu lar rejection from recu rrent 60. Cabezuelo JB, Ramirez P, Acosta F, et al. Does the standard vs piggyback
hep atitis C in liver transp lant p atients. Liver Transpl 2009;15:216–222. surgical technique affect the development of early acute renal failure
34. Toyoki Y, Renz JF, Mu d ge C, et al. Allograft rejection in p ed iatric liver after orthotopic liver transplantation? Transplant Proc. 2003;35: 1913–1914.
transplantation: com parison betw een cad averic and living related 61. Belghiti J, Panis Y, Sau vanet A, et al. A new techniqu e of sid e to sid e
d onors. Pediatr Transplant 2002;6:301–307. caval anastom osis d u ring orthotop ic hep atic transp lantation w ithou t
35. Wiesner RH , Rakela J, Ishitani MB, et al. Recent ad vances in liver inferior vena caval occlu sion. Surg Gynecol Obstet 1992;175:270–272.
transp lantation. Mayo Clin Proc 2003;78:197–210. 62. Sonnend ay CJ, Mathur AK, Lee DS, et al. The sid e-to-sid e cavocavos-
36. Ramji A, Yoshida EM, Bain VG, et al. Late acute rejection after liver trans- tom y techniqu e elim inates hepatic venou s outflow stenosis in ortho-
plantation: the Western Canada experience. Liver Transpl 2002;8:945–951. topic liver transp lantation. Liver Transpl 2009;15:S168.
37. Lu d w ig J, Wiesner RH , Batts KP, et al. The acu te vanishing bile d u ct 63. Mehrabi A, Mood ZA, Fonou ni H , et al. A single-center exp erience of
synd rom e (acu te irreversible rejection) after orthotop ic liver trans- 500 liver transp lants u sing the m od ified p iggyback techniqu e by Bel-
p lantation. Hepatology 1987;7:476–483. ghiti. Liver Transpl 2009;15:466–474.
64. Mu rray BM, Paller MS. Beneficial effects of renal d enervation and 87. Jau har S, Talw alkar JA, Schneekloth T, et al. Analysis of factors that
prazosin on GFR and renal blood flow after cyclosp orine in rats. Clin p red ict alcohol relapse follow ing liver transp lantation. Liver Transpl
Nephrol 1986;25(Sup p l 1):S37–S39. 2004;10:408–411.
65. Lin CC, Chuang FR, Lee CH , et al. The renal-sp aring efficacy of basil- 88. Ku gelm as M, Sp iegelm an P, Osgood MJ, et al. Different im m u nosu p -
ixim ab in ad u lt living d onor liver transp lantation. Liver Transpl 2005; p ressive regim ens and recu rrence of prim ary sclerosing cholangitis
11:1258–1264. after liver transp lantation. Liver Transpl 2003;9:727–732.
66. Em re S, Gond olesi G, Polat K, et al. Use of d aclizu m ab as initial 89. Molm enti EP, N etto GJ, Mu rray N G, et al. Incid ence and recu rrence of
im m u nosupp ression in liver transplant recipients w ith im paired au toim m une/ alloim m u ne hepatitis in liver transplant recip ients.
renal fu nction. Liver Transpl 2001;7:220–225. Liver Transpl 2002;8:519–526.
67. Eckhoff DE, McGu ire B, Sellers M, et al. The safety and efficacy of a 90. Sylvestre PB, Batts KP, Bu rgart LJ, et al. Recu rrence of p rim ary biliary
tw o-d ose d aclizu m ab (zenap ax) ind u ction therap y in liver transplant cirrhosis after liver transplantation: histologic estim ate of incid ence
recip ients. Transplantation 2000;69:1867–1872. and natural history. Liver Transpl 2003;9:1086–1093.
68. Calm u s Y, Kam ar N , Gu genheim J, et al. Assessing renal fu nction w ith 91. H eneghan MA, Zolfino T, Mu iesan P, et al. An evalu ation of long-term
d aclizu m ab ind u ction and d elayed tacrolim u s introd u ction in liver outcom es after liver transp lantation for cryp togenic cirrhosis. Liver
transplant recip ients. Transplantation 2010;89:1504–1510. Transpl 2003;9:921–928.
69. Solim an T, H etz H , Bu rghu ber C, et al. Short-term ind u ction therap y 92. Parkin DM, Bray F, Ferlay J, et al. Estim ating the w orld cancer bu rd en:
w ith anti-thym ocyte globulin and d elayed use of calcineurin Globocan 2000. Int J Cancer 2001;94:153–156.
inhibitors in orthotop ic liver transp lantation. Liver Transpl 2007;13: 93. Mazzaferro V, Regalia E, Doci R, et al. Liver transp lantation for the
1039–1044. treatm ent of sm all hep atocellu lar carcinom as in patients w ith cirrho-
70. Tchervenkov JI, Tzim as GN , Cantarovich M, et al. The im p act of thy- sis. N Engl J Med 1996;334:693–699.
m oglobulin on renal fu nction and calcineu rin inhibitor initiation in 94. Kornberg A, Ku p per B, Tannap fel A, et al. Ad ju vant conversion to
recip ients of orthotopic liver transp lant: a retrosp ective analysis of 298 sirolim us in liver transplant patients w ith recurrent hepatocellu lar
consecu tive p atients. Transplant Proc 2004;36:1747–1752. carcinom a—p relim inary resu lts. Transpl Int 2008;21:96–99.
71. Bajjoka I, H saiky L, Brow n K, et al. Preserving renal fu nction in liver 95. Gom ez-Cam arero J, Salced o M, Rincon D, et al. Use of everolim u s as a
transplant recipients w ith rabbit anti-thym ocyte globulin and d elayed rescue im m u nosup pressive therapy in liver transplant patients w ith
initiation of calcineurin inhibitors. Liver Transpl 2008;14:66–72. neop lasm s. Transplantation 2007;84:786–791.
72. Cohen AJ, Stegall MD, Rosen CB, et al. Chronic renal d ysfu nction late 96. Kornberg A, Ku pp er B, Tannap fel A, et al. Long-term su rvival after
after liver transplantation. Liver Transpl 2002;8:916–921. recu rrent hep atocellu lar carcinom a in liver transp lant p atients: clini-
73. Gonw a TA, Mai ML, Melton LB, et al. End -stage renal d isease (ESRD) cal p atterns and ou tcom e variables. Eur J Surg Oncol 2010;36:275–280.
after orthotopic liver transp lantation (OLTX) u sing calcineu rin-based 97. Yeganeh M, Finn RS, Saab S. Ap p arent rem ission of a solitary m etasta-
im m u notherapy: risk of d evelop m ent and treatm ent. Transplantation tic p u lm onary lesion in a liver transp lant recip ient treated w ith
2001;72:1934–1939. sorafenib. Am J Transplant 2009;9:2851–2854.
74. Ojo AO, H eld PJ, Port FK, et al. Chronic renal failu re after transp lanta- 98. Bu rd ick JF, Vogelsang GB, Sm ith WJ, et al. Severe graft-versu s-host
tion of a nonrenal organ. N Engl J Med 2003;349:931–940. d isease in a liver-transp lant recip ient. N Engl J Med 1988;318:689–691.
75. N air S, Eason J, Loss G. Sirolim u s m onotherap y in nep hrotoxicity d ue 99. Thin L, Macqu illan G, Ad am s L, et al. Acu te graft-versu s-host d isease
to calcineurin inhibitors in liver transp lant recip ients. Liver Transpl after liver transplant: novel u se of etanercept and the role of tu m or
2003;9:126–129. necrosis factor alp ha inhibitors. Liver Transpl 2009;15:421–426.
76. Raim ond o ML, Dagher L, Pap atheod orid is GV, et al. Long-term 100. Sanchez-Izquierd o JA, Lu m breras C, Colina F, et al. Severe graft ver-
m ycophenolate m ofetil m onotherapy in com bination w ith calcineu rin su s host d isease follow ing liver transp lantation confirm ed by PCR-
inhibitors for chronic renal d ysfunction after liver transplantation. H LA-B sequ encing: report of a case and literatu re review.
Transplantation 2003;75:186–190. Hepatogastroenterology 1996;43:1057–1061.
77. Masetti M, Montalti R, Rom p ianesi G, et al. Early w ithd raw al of cal- 101. Ku sne S, Du m m er JS, Singh N , et al. Infections after liver transp lanta-
cineurin inhibitors and everolim u s m onotherapy in d e novo liver tion. An analysis of 101 consecutive cases. Medicine (Baltimore) 1988;67:
transp lant recipients p reserves renal fu nction. Am J Transplant 132–143.
2010;10:2252–2262. 102. Pelletier SJ, Crabtree TD, Gleason TG, et al. Characteristics of infec-
78. Karie-Gu igu es S, Janu s N , Saliba F, et al. Long-term renal fu nction in tious com plications associated w ith m ortality after solid organ trans-
liver transplant recipients and im pact of im m u nosupp ressive regi- plantation. Clin Transplant 2000;14:401–408.
m ens (calcineu rin inhibitors alone or in com bination w ith m ycophe- 103. Kibbler CC. Infections in liver transp lantation: risk factors and strate-
nolate m ofetil): the TRY stu d y. Liver Transpl 2009;15:1083–1091. gies for p revention. J Hosp Infect 1995;30(Su p p l):209–217.
79. N eau -Cransac M, Morel D, Bernard PH , et al. Renal failu re after liver 104. Saw yer RG, Crabtree TD, Gleason TG, et al. Im p act of solid organ
transp lantation: ou tcom e after calcineu rin inhibitor w ithd raw al. Clin transplantation and im m u nosu p p ression on fever, leu kocytosis, and
Transplant 2002;16:368–373. physiologic response d u ring bacterial and fu ngal infections. Clin
80. Rogers CC, Johnson SR, Mand elbrot DA, et al. Tim ing of sirolim u s Transplant 1999;13:260–265.
conversion influ ences recovery of renal fu nction in liver transplant 105. N air S, Cohen DB, Cohen MP, et al. Postop erative m orbid ity, m ortal-
recip ients. Clin Transplant 2009;23:887–896. ity, costs, and long-term su rvival in severely obese p atients u nd ergo-
81. Watson CJ, Gim son AE, Alexand er GJ, et al. A rand om ized controlled ing orthotop ic liver transp lantation. Am J Gastroenterol 2001;96:
trial of late conversion from calcineu rin inhibitor (CN I)-based to 842–845.
sirolim us-based im m u nosup pression in liver transp lant recipients 106. Wad e JJ, Roland o N , H ayllar K, et al. Bacterial and fu ngal infections
w ith im p aired renal fu nction. Liver Transpl 2007;13:1694–1702. after liver transplantation: an analysis of 284 p atients. Hepatology
82. H irose R, Roberts JP, Qu an D, et al. Exp erience w ith d aclizu m ab in 1995;21:1328–1336.
liver transp lantation: renal transplant d osing w ithout calcineu rin 107. Wallot MA, Mathot M, Janssen M, et al. Long-term su rvival and late
inhibitors is insu fficient to prevent acute rejection in liver transplanta- graft loss in p ed iatric liver transp lant recip ients—a 15-year single-
tion. Transplantation 2000;69:307–311. center experience. Liver Transpl 2002;8:615–622.
83. Fong TL, Bu nnap rad ist S, Jord an SC, et al. Analysis of the United N et- 108. Sharpe MD, Ghent C, Grant D, et al. Efficacy and safety of itracona-
w ork for Organ Sharing d atabase com paring renal allografts and zole p rop hylaxis for fu ngal infections after orthotopic liver transplan-
p atient su rvival in com bined liver-kid ney transp lantation w ith the tation: a prosp ective, rand om ized , d ou ble-blind stu d y. Transplantation
contralateral allografts in kid ney alone or kid ney-p ancreas transp lan- 2003;76:977–983.
tation. Transplantation 2003;76:348–353. 109. Lind en PK, Coley K, Fontes P, et al. Invasive asp ergillosis in liver
84. Ghobrial RM. Retransp lantation for recurrent hepatitis C. Liver Transpl transplant recipients: outcom e com parison of therapy w ith am p ho-
2002;8:S38–S43. tericin B lipid com p lex and a historical cohort treated w ith conven-
85. Charlton M. The im p act of ad vancing d onor age on histologic recur- tional am photericin B. Clin Infect Dis 2003;37:17–25.
rence of hep atitis C infection: the p erils of ignored m aternal ad vice. 110. H u ang DZ, Le GR, Zhang QP, et al. The valu e of color Dop p ler u ltra-
Liver Transpl 2003;9:535–537. sonography in m onitoring norm al orthotop ic liver transplantation
86. Pelletier SJ, Schaubel DE, Pu nch JD, et al. H ep atitis C is a risk factor and p ostop erative com p lications. Hepatobiliary Pancreat Dis Int 2003;2:
for d eath after liver retransp lantation. Liver Transpl 2005;11:434–440. 54–58.
111. Glockner JF, Forau er AR, Solom on H , et al. Three-d im ensional 136. Frazer CK, Gu pta A. Stenosis of the hep atic vein anastom osis after
gad oliniu m -enhanced MR angiograp hy of vascu lar com p lications liver transp lantation: treatm ent w ith a heparin-coated m etal stent.
after liver transplantation. AJR Am J Roentgenol 2000;174:1447–1453. Australas Radiol 2002;46:422–425.
112. Oh CK, Pelletier SJ, Saw yer RG, et al. Uni- and m u lti-variate analysis 137. Welling TH , H eid t DG, Englesbe MJ, et al. Biliary com p lications fol-
of risk factors for early and late hep atic artery throm bosis after liver low ing liver transplantation in the m od el for end -stage liver d isease
transplantation. Transplantation 2001;71:767–772. era: effect of d onor, recip ient, and technical factors. Liver Transpl 2008;
113. Sheiner PA, Varm a CV, Gu arrera JV, et al. Selective revascu larization 14:73–80.
of hepatic artery throm boses after liver transplantation im proves 138. Feller RB, Waugh RC, Selby WS, et al. Biliary strictu res after liver
patient and graft su rvival. Transplantation 1997;64:1295–1299. transplantation: clinical p ictu re, correlates and ou tcom es. J Gastroen-
114. Bhattacharjya S, Gu nson BK, Mirza DF, et al. Delayed hepatic artery terol Hepatol 1996;11:21–25.
throm bosis in ad u lt orthotop ic liver transp lantation—a 12-year exp e- 139. Saw yer RG, Pu nch JD. Incid ence and m anagem ent of biliary com p li-
rience. Transplantation 2001;71:1592–1596. cations after 291 liver transp lants follow ing the introd u ction of tran-
115. Mas VR, Fisher RA, Malu f DG, et al. H ep atic artery throm bosis after scystic stenting. Transplantation 1998;66:1201–1207.
liver transplantation and genetic factors: p rothrom bin G20210 A poly- 140. Rou m ilhac D, Poyet G, Sergent G, et al. Long-term resu lts of p ercu ta-
m orp hism . Transplantation 2003;76:247–249. neous m anagem ent for anastom otic biliary strictu re after orthotopic
116. Pu ngp apong S, Manzarbeitia C, Ortiz J, et al. Cigarette sm oking is liver transp lantation. Liver Transpl 2003;9:394–400.
associated w ith an increased incid ence of vascu lar com p lications after 141. Sung RS, Campbell DA Jr, Rudich SM, et al. Long-term follow-up of per-
liver transp lantation. Liver Transpl 2002;8:582–587. cutaneous transhepatic balloon cholangioplasty in the management of bil-
117. Singhal A, Stokes K, Sebastian A, et al. End ovascu lar treatm ent of iary strictures after liver transplantation. Transplantation 2004;77:110–115.
hep atic artery throm bosis follow ing liver transp lantation. Transpl Int 142. Marcos A, Fisher RA, H am JM, et al. Right lobe living d onor liver
2010;23:245–256. transp lantation. Transplantation 1999;68:798–803.
118. Singhal A, Mu kherjee I, Stokes K, et al. Continu ou s intraarterial 143. Nishid a S, Nakamura N, Kad ono J, et al. Intrahepatic biliary strictures
throm bolysis for early hep atic artery throm bosis follow ing liver after liver transplantation. J Hepatobiliary Pancreat Surg 2006;13:511–516.
transp lantation: case rep ort. Vasc Endovasc Surg 2010;44:134–138. 144. Grew al H P, Willingham DL, N gu yen J, et al. Liver transp lantation
119. Kim BW, Won JH , Lee BM, et al. Intraarterial throm bolytic treatm ent u sing controlled d onation after card iac d eath d onors: an analysis of a
for hepatic artery throm bosis im m ed iately after living d onor liver large single-center exp erience. Liver Transpl 2009;15:1028–1035.
transplantation. Transplant Proc 2006;38:3128–3131. 145. Maheshw ari A, Maley W, Li Z, et al. Biliary com p lications and ou t-
120. Pinna AD, Sm ith CV, Fu ru kaw a H , et al. Urgent revascu larization of com es of liver transplantation from d onors after card iac d eath. Liver
liver allografts after early hep atic artery throm bosis. Transplantation Transpl 2007;13:1645–1653.
1996;62:1584–1587. 146. Murray JE, Merrill JP, H arrison JH . Kid ney transp lantation betw een
121. Abbasoglu O, Levy MF, Vod ap ally MS, et al. H ep atic artery stenosis seven pairs of id entical tw ins. Ann Surg 1958;148:343–359.
after liver transp lantation—incid ence, p resentation, treatm ent, and 147. Starzl TE. Living d onors: con. Transplant Proc 1987;19:174–175.
long term outcom e. Transplantation 1997;63:250–255. 148. Johnson EM, And erson JK, Jacobs C, et al. Long-term follow -u p of liv-
122. Maruzzelli L, Miraglia R, Caru so S, et al. Percu taneou s end ovascu lar ing kid ney d onors: qu ality of life after d onation. Transplantation
treatm ent of hepatic artery stenosis in ad ult and ped iatric patients 1999;67:717–721.
after liver transp lantation. Cardiovasc Intervent Radiol 2010;33: 149. Miller C, Florm an S, Kim -Schlu ger L, et al. Fu lm inant and fatal gas
1111–1119. gangrene of the stom ach in a healthy live liver d onor. Liver Transpl
123. Johnston T, Jeon H , Ged aly R, et al. Im portance of local infection in 2004;10:1315–1319.
hepatic artery pseu d oaneu rysm s. Liver Transpl 2008;14:388. 150. Trotter JF, Ad am R, Lo CM, et al. Docu m ented d eaths of hep atic lobe
124. Bonham CA, Kap u r S, Geller D, et al. Excision and im m ed iate revas- d onors for living d onor liver transp lantation. Liver Transpl 2006;12:
cu larization for hepatic artery pseud oaneurysm follow ing liver trans- 1485–1488.
plantation. Transplant Proc 1999;31:443. 151. Cronin DC II, Millis JM, Siegler M. Transp lantation of liver grafts from
125. Sied ers E, Peeters PM, TenVergert EM, et al. Early vascu lar com p lica- living d onors into ad u lts–too m u ch, too soon. N Engl J Med 2001;344:
tions after p ed iatric liver transp lantation. Liver Transpl 2000;6:326–332. 1633–1637.
126. Englesbe MJ, Ku bu s J, Mu ham m ad W, et al. Portal vein throm bosis 152. Brow n RS Jr, Ru sso MW, Lai M, et al. A su rvey of liver transp lantation
and su rvival in p atients w ith cirrhosis. Liver Transpl 2010;16:83–90. from living ad ult d onors in the United States. N Engl J Med 2003;348:
127. Bhattacharjya T, Olliff SP, Bhattacharjya S, et al. Percu taneou s p ortal 818–825.
vein throm bolysis and end ovascu lar stent for m anagem ent of p ost- 153. Um eshita K, Fu jiw ara K, Kiyosaw a K, et al. Op erative m orbid ity of
transp lant p ortal venou s cond u it throm bosis. Transplantation 2000;69: living liver d onors in Jap an. Lancet 2003;362:687–690.
2195–2198. 154. Broering DC, Wilm s C, Bok P, et al. Evolu tion of d onor m orbid ity in
128. Cherukuri R, Haskal ZJ, Naji A, et al. Percutaneous thrombolysis and living related liver transp lantation: a single-center analysis of 165
stent placement for the treatment of portal vein thrombosis after liver cases. Ann Surg 2004;240:1013–1024; d iscu ssions 1024–1026.
transplantation: long-term follow-up. Transplantation 1998;65:1124–1126. 155. Ghobrial RM, Freise CE, Trotter JF, et al. Donor m orbid ity after living
129. Gonzalez-Tu tor A, Abascal F, Cerezai L, et al. Transju gular ap p roach d onation for liver transp lantation. Gastroenterology 2008;135:468–476.
to treat p ortal vein stenosis after liver transp lantation—a case rep ort. 156. Yi N J, Su h KS, Cho JY, et al. Three-qu arters of right liver d onors exp e-
Angiology 2000;51:511–514. rienced p ostoperative com p lications. Liver Transpl 2007;13:797–806.
130. Peru m alla R, Jam ieson N V, Praseed om RK. Left renal vein as an 157. Ito T, Kiu chi T, Egaw a H , et al. Su rgery-related m orbid ity in living
op tion for p ortal inflow in liver transp lant recip ients w ith p ortal vein d onors of right-lobe liver graft: lessons from the first 200 cases. Trans-
throm bosis. Transpl Int 2008;21:701–703. plantation 2003;76:158–163.
131. Glanem ann M, Settm acher U, Langrehr JM, et al. Resu lts of end -to- 158. Shiffm an ML, Brow n RS Jr, Olthoff KM, et al. Living d onor liver trans-
end cavocavostom y d u ring ad u lt liver transp lantation. World J Surg plantation: sum m ary of a conference at The N ational Institutes of
2002;26:342–347. H ealth. Liver Transpl 2002;8:174–188.
132. N avarro F, Le Moine MC, Fabre JM, et al. Sp ecific vascu lar com p lica- 159. Lo CM. Com p lications and long-term ou tcom e of living liver d onors:
tions of orthotop ic liver transp lantation w ith p reservation of the a su rvey of 1,508 cases in five Asian centers. Transplantation 2003;75:
retrohepatic vena cava: review of 1361 cases. Transplantation 1999;68: S12–S15.
646–650. 160. Egaw a H , Inom ata Y, Uem oto S, et al. Biliary anastom otic com p lica-
133. N em ec P, Cerny J, H okl J, et al. H em od ynam ic m easu rem ent in liver tions in 400 living related liver transp lantations. World J Surg 2001;25:
transplantation. Piggyback versu s conventional techniqu es. Ann 1300–1307.
Transplant 2000;5:35–37. 161. Inom ata Y, Uem oto S, Asonu m a K, et al. Right lobe graft in living
134. Parrilla P, Sanchez-Bu eno F, Figu eras J, et al. Analysis of the com p lica- d onor liver transp lantation. Transplantation 2000;69:258–264.
tions of the piggy-back techniqu e in 1,112 liver transp lants. Transplan- 162. Kiu chi T, Tanaka K, Ito T, et al. Sm all-for-size graft in living d onor liver
tation 1999;67:1214–1217. transp lantation: how far shou ld w e go? Liver Transpl 2003;9:S29–S35.
135. Borsa JJ, Daly CP, Fontaine AB, et al. Treatm ent of inferior vena cava 163. Boillot O, Mechet I, Le Derf Y, et al. Portom esenteric d isconnection for
anastom otic stenoses w ith the Wallstent end op rosthesis after ortho- sm all-for-size grafts in liver transp lantation: preclinical stud ies in
topic liver transp lantation. J Vasc Interv Radiol 1999;10:17–22. p igs. Liver Transpl 2003;9:S42–S46.
CHAPTER
49
Complications of
Pancreatic Transplantation
Dixon B. Kaufman
■ RATIONALE OF PANCREATIC betes typ ically exhibit w id e d eviations of p lasm a glu cose
levels from hou r to hou r and from d ay to d ay. Becau se
TRANSPLANTATION FOR PATIENTS
hyp oglycemia is intolerable, glu cose control m u st err on
WITH TYPE 1 DIABETES MELLITUS the high sid e. Therefore, p atients m u st live w ith relative
The prevalence of typ e 1 d iabetes in the United States is chronic hyperglycem ia.
estim ated to be 1,000,000 ind ivid uals, and 35,000 new cases The only treatm ents that influ ence the p rogression of
are d iagnosed each year. The d iscovery of insu lin as a ther- second ary com p lications inclu d e -cell rep lacem ent ther-
ap eutic agent in 1927 revolutionized the treatm ent of d ia- ap y w ith p ancreas or islet transp lantation and intensive
betes m ellitu s by changing it from a rapid ly fatal d isease insu lin therap y. Since d iabetes is not a rap id ly fatal d isease,
into a chronic illness. Unfortunately, this increased longevity and becau se transp lant p roced u res requ ire the p atient to
brought to the fore serious secondary complications, inclu d - receive life-long im m u nosu p p ression, the resu lts of islet or
ing nep hrop athy, neurop athy, retinopathy, and m acrovas- p ancreas transp lantation m u st be su fficiently efficacious
cu lar and m icrovascular com p lications in su rvivors 10 to and safe to w arrant ap p lication in p lace of stand ard med -
20 years after d isease onset. The m etabolic, m icrovascu lar, ical m anagem ent of the p rim ary d isease. Cu rrently, islet
and m acrovascu lar com plications of d iabetes are resp onsi- transp lantation is an exp erim ental p roced u re for highly
ble for increased m ortality in patients w ith type 1 d iabetes selective cases. Pancreas transp lantation is a p roven thera-
com p ared w ith the general US p op u lation (1). In 2002, the p eu tic treatm ent op tion for d iabetes and is su perior to
national d irect and ind irect costs of typ e 1 and typ e 2 d ia- manu al intensive insu lin therapy w ith regard to the effi-
betes, inclu d ing hosp ital and p hysician care, laboratory cacy of achieving glycem ic control and beneficial effects on
tests, p harm aceu tical p rod u cts, and p atient w orkd ays d iabetic second ary com p lications.
lost becau se of d isability and prem atu re d eath, exceed ed A successful pancreas transplant prod uces an immed i-
$130 billion (2). ate normoglycem ic and insu lin-ind ep end ent state that nor-
H yp erglycem ia is the m ost im p ortant factor in the malizes hemoglobin A1C levels for as long as the graft
d evelop m ent and p rogression of second ary com p lications functions. Transplantation also has the ad d ed physiological
of d iabetes. The Diabetes Control and Com p lication Trial properties of proinsu lin and C-peptid e release not possible
d em onstrated that the m icrovascu lar and , p ossibly, w ith intensive insulin therapy (5). Through improved meta-
m acrovascu lar com p lications of d iabetes m ay be p revented bolic control, many second ary com plications of d iabetes,
by m aintaining eu glycem ia (3,4). This realization has led to inclu d ing d iabetic neu ropathy (6), au tonom ic neu rop athy-
a search for alternative m ethod s of treatm ent d esigned to associated su d d en d eath (7), and d iabetic nephropathy in
achieve better glycem ic control so that the progression of both u remic and nonuremic p atients (8,9) m ay be marked ly
long-term com p lications can be altered . im proved . A su ccessfu l pancreas transplant significantly
Cu rrently, there is no practical artificial end ocrine p an- improves qu ality of life (10) and life expectancy (11,12).
creas, a m echanical insu lin-d elivery d evice cou pled w ith App roxim ately 1,300 pancreas transplants are per-
an au tom ated glu cose-sensory system that cou ld ad m inis- formed annually in the United States. Of these, 65% to 70%
ter insulin w ith the d egree of control necessary to prod u ce involve a sim u ltaneous pancreas and kid ney (SPK) trans-
a near-constant eu glycem ic state w ithout risk of hyp o- plant for p atients w ith type 1 d iabetes and chronic renal fail-
glycem ia. Since severe hypoglycem ia is life threatening, ure. These ind ivid u als are excellent cand id ates for an SPK
p ersons w ith typ e 1 d iabetes are resigned to m anually reg- transplant from the same d onor because the immunosup-
u lating blood glu cose levels by various form s of insulin pressive med ications that are need ed are similar to those for
ad m inistration. As a consequ ence, patients w ith type 1 d ia- a kid ney transplant alone and the su rgical risk of ad d ing the
pancreas is low. The benefits of ad d ing a pancreas trans-
plant to ameliorate d iabetes are profou nd —transplantation
saves lives (11,12). The second category for pancreas trans-
Dixon B. Kaufman: Dep artm ent of Su rgery. Division of plantation consists of patients w ith type 1 d iabetes w ho
Transp lantation, University of Wisconsin (Mad ison).
640
Chapter 49 • Complications of Pancreatic Transplantation 641
have received a previous kid ney transplant from either a tion. Patients are treated w ith a short cou rse of anti-T-cell
living or d eceased d onor. This grou p accou nts for app roxi- antibod y, often in conju nction w ith corticosteroid s.
mately 20% of p atients receiving pancreas transp lants. The The most valuable and complete information on the
im portant consid eration is that of su rgical risk, since the resu lts of p ancreas transplantation com es from tw o sou rces,
risk of immunosuppression has alread y been assumed . nam ely, the International Pancreas Transplant Registry
The third category for p ancreas transp lantation is com - (IPTR) and the Scientific Registry of Transplant Recipients
posed of nonu rem ic patients w ith type 1 d iabetes. In this (SRTR) of the Organ Procurement and Transplant N etw ork
situ ation, one assesses the risk of im m unosup pression to be (OPTN ). The SRTR is the scientific arm of the OPTN , w here
less than the risk of d iabetes treated w ith conventional d ata on all transp lants in the United States have been col-
exogenou s insu lin. Som e of these patients w ith d iabetes lected since 1987. The SRTR su p p orts ongoing evalu ation
have extrem ely labile d isease, such that there is d ifficu lty of the scientific and clinical statu s of solid -organ transp lan-
w ith d ay-to-d ay living associated w ith frequ ent em ergency tation, inclu d ing p ancreas transp lants. Fu nd ing comes
room visits and inp atient hosp italizations for hyp o- from the H ealth Resou rces and Services Ad m inistration,
glycem ia or d iabetic ketoacid osis. Other patients have sig- a d ivision of the U.S. Dep artm ent of H ealth and H u m an
nificant d ifficulty w ith hypoglycem ic unaw areness that Services. The SRTR is ad m inistered by Arbor Research,
resu lts in u nconsciou sness w ithou t w arning. For select a n on p rofit h ealth research organ ization, based in Ann
patients, this state can be a d evastating problem that affects Arbor, MI.
their em p loym ent and their ability to keep a d river ’s In ad d ition to the national d atabases, mu lticenter stud -
license and creates concern abou t lethal hypoglycem ia ies and single-center experiences w ith pancreas transplan-
w hile asleep . Pretransplant evaluation often incorp orates tation have also been valu able in rep orting resu lts of
an assessm ent of the Clarke Score (13) to sem iqu antita- sp ecific technical and im m u nosu p p ressive p rotocols.
tively d eterm ine the severity of hyp oglycem ic com p lica- Figu re 49.1 show s p atient, kid ney, and p ancreas graft
tions in an effort to m ore fully und erstand the risk–benefit su rvival rates in SPK transp lant recip ients in the m ost
relationship for u nd ergoing a p ancreas or islet transp lant. recent era analyzed (2000 to 2006) by the IPTR. These are
the best ou tcom es rep orted to d ate, w ith 1-year patient,
kid ney, and p ancreas graft su rvival rates of 95%, 92%, and
■ OUTCOME MEASURES OF
85%, resp ectively.
PANCREATIC TRANSPLANTATION Figu re 49.2 show s the com p arative su rvival rates of the
The m ost im p ortant ou tcom e m easu res of p ancreas trans- p ancreas graft am ong the three transp lant group s [SPK,
plantation are d efined in term s of patient and graft su rvival p ancreas after kid ney (PAK), and p ancreas transplant alone
and rejection. The d efinition of patient survival is obviou s. (PTA)] for the cu rrent era analyzed . These results d em on-
Pancreas graft losses are d efined as (a) patient d eath w ith a strate that p ancreas allograft loss com m only occu rs.
fu nctioning graft or (b) loss of insu lin ind epend ence irre-
sp ective of w hether the p ancreas allograft is in p lace or ■ General causes and incidence
rem oved . Rejection is an im m unologic host response to the
of pancreas graft loss
foreign graft that w ill d estroy it unless antirejection m ed -
ications are effectively ad m inistered . The d efinition of a The tw o most im portant general categories of graft loss are
rejection ep isod e u su ally requ ires tissu e biop sy confirm a- technical and im m u nological. The m ost com m on cause of
100 FIGURE 49.1. Patient, kidney, and pancreas

survival rates of simultaneous pancreas–
kidney transplant recipients (n 6102, January
80 1, 2000, to December 31, 2006). (Adapted from
International Pancreas Transplant Registry,
2007.)
Survival (%)
60
40
Category 1 year survival
Patient 95%
20 Kidney 92%
Pancreas 84%
0
0 12 24 36
Months posttransplant
FIGURE 49.2. Pancreas transplant sur- 100

vival rates according to transplant category
(2000 to 2006). SPK, simultaneous pancreas
and kidney; PAK, pancreas after kidney; PTA, 80
pancreas transplant alone. (Adapted from
International Pancreas Transplant Registry,
2007.)
Survival (%)
60
40
Category N 1 year survival
SPK 3,885 83%
20 PAK 630 79%
PTA 290 78%
0
0 12 24 36
Months posttransplant
p ancreas graft failu re w ith in the first 6 m onth s p ost- ■ Pancreas transplant recipient selection
transp lan t in all three recipient categories is technical. The
absolu te rate of p ancreas graft loss w ithin the first 6 m onths In the evalu ation phase of a p ancreas transplant cand id ate,
post-transp lant is approxim ately 10% in SPK transp lant the history of d isease, the review of system s, and the phys-
recipients and 20% in PAK transp lant and PTA recip ients. ical exam ination are cond u cted in a m anner that focu ses on
Technical failu res accou nt for 60% of the cases of p an- specific com orbid cond itions that m ay com prom ise trans-
creas graft loss w ithin this early tim e period . Know led ge of p lant ou tcom e. Contraind ications to solitary p ancreas
the technical asp ects of the su rgical p roced u res p ertaining tran sp lan tation in clu d e p atients w ith typ e 1 d iabetes
to p retransp lant organ p rocu rem ent and p ancreas graft w h o h ave n orm al renal fu n ction and d o n ot exh ibit a brit-
im plantation shed light on the potential com plications of tle cou rse, hyp oglycem ic u naw areness, or evid en ce of
pancreas transp lantation. The m ost im portant cau se of n ep hrop athy. Often tim es the Clarke Score is u tilized to
technical failu re is p ancreas graft throm bosis. It occu rs in d eterm ine the threshold of severity of hyp oglycem ic com -
approxim ately 4% to 9% of cases. SPK transp lant recip ients p lications that m ight ju stify a solitary pancreas transplant.
are at the low est risk, and PTA recipients are at the highest For p atients w ho have an ind ication for p ancreas trans-
risk. Graft losses d u e to infection, pancreatitis, bleed ing, or p lantation, it is im p ortant to exclu d e significant m ed ical
a d u od enal leak are relatively rare. contraind ications, inclu d ing recent m alignancy, active or
Im m u nologic cau ses of graft loss, acute and chronic ch ron ic u ntreated in fection , ad vanced form s of m ajor
rejection, becom e more im portant after the 6-m onth p eriod . extraren al d isease (i.e., coronary artery d isease), life
The absolu te rate of p ancreas graft loss from rejection exp ectan cy of 1 year, sensitization to d on or tissu e, non-
w ithin the first year p ost-transp lant is actu ally very low. com p liance, active su bstance abu se, and u ncontrolled psy-
The cu rrent rate of im m u nologic loss in SPK transp lant chiatric d isord er (Table 49.1).
recipients is only 2% at 1 year. The im m u nologic risk for Preexisting morbidities have direct implications for pre-
graft loss for the technically su ccessfu l cases of PAK trans- d icting and, therefore, avoiding postoperative complications.
plant and PTA has been red uced to only 3% to 5% at 1 year. Prem ature card iovascular d isease and ad vanced coronary
Patient d eath at a tim e w hen the transp lanted organs are
fu nctional is another im portant cause of graft loss, esp e-
Table 4 9 .1 Con t r a in d ica t ion s t o p a n cr ea s
cially in the SPK and PAK transplant category.
t ra n sp la n t a t ion
1. Omission of consent for organ donation from family
■ COMPLICATIONS OF PANCREATIC 2. Incompatible blood group
3. Donor HLA class I antigen generating a positive immunological
TRANSPLANTATION crossmatch
Pancreas transp lant recipients m ay exp erience several 4. History of type 1 or type 2 diabetes mellitus in donor
5. Donor viral infectious disease of HIV, hepatitis B and/or C
com m on and potentially life-threatening com plications.
6. Significant bacterial and/or fungal infection of the donor
Com p lications m ay be anticipated and averted in the set-
7. Significant and prolonged donor hemodynamic instability
tings of recip ient selection, d onor selection and procu re- 8. History of previous donor pancreatic surgery
ment, and p ancreas transplantation surgery and in the 9. Intra-abdominal trauma to the donor pancreas
postoperative m anagem ent setting.
artery d isease are the m ost im p ortant com orbid ities in The com bination of orthostatic hyp otension and recu m -
patients w ith typ e 1 d iabetes, especially those w ith d iabetic bent hypertension resu lts from d ysregu lation of vascu lar
nep hrop athy (14–16). There is a fou rfold elevation in car- tone. This cond ition has im p lications for blood pressure
d iovascu lar m ortality in type 1 d iabetics w ithou t p rotein- control p ost-transp lant, esp ecially in p atients w ith blad d er-
uria com p ared w ith the general popu lation. In typ e 1 d rained p ancreas transp lants that are p red isp osed to vol-
d iabetics w ith p roteinuria, card iovascular m ortality is 37 u m e d ep letion. Carefu l reassessm ent of p ost-transp lant
tim es higher than it is in the general popu lation (15). The antihyp ertensive med ication requ irem ent is im portant.
d iabetic, u rem ic patient has several risk factors in ad d ition Diabetic retinop athy is a nearly u biqu itou s find ing in
to d iabetes for the d evelop m ent of coronary artery d isease, p atients w ith d iabetes and end -stage renal d isease. Blind -
inclu d ing hyp ertension, hyperlip id em ia, and sm oking. ness is not an absolu te contraind ication to transp lantation
Because of the neu ropathy associated w ith d iabetes, since m any blind patients lead very ind epend ent life styles.
patients are often asym ptom atic because ischem ia-ind u ced Althou gh rarely a p roblem , it shou ld be confirm ed that a
angina is not p erceived . The prevalence of significant p atient w ith significant vision loss has an ad equ ate sup port
( 50% stenosis) coronary artery d isease in patients w ith system to ensure help w ith travel and im m unosuppressive
d iabetes starting treatm ent for end -stage renal d isease is m ed ications.
estim ated to be 45% to 55%. Low er extrem ity p erip heral vascu lar d isease is signifi-
The interventional screening stu d ies to d etect significant in p atients w ith d iabetes. Urem ic d iabetic patients are
cant, treatable coronary artery d isease requ ire a u niform at risk for am p u tation of a low er extrem ity. These p roblem s
method ology. N oninvasive screening that has high sensi- typically begin w ith a foot ulcer associated w ith ad vanced
tivity and sp ecificity for significant coronary artery d isease som atosensory neu rop athy. The risk is fu rther com p licated
can be u sed in low -risk p atients. Patients consid ered at by sensory and m otor neuropathies in patients w ith long-
mod erate or high risk for significant coronary artery d is- stand ing d iabetes. Vascu lar d isease m ay have im plications
ease shou ld u nd ergo coronary arteriography to d eterm ine for the rehabilitation p ost-transp lant and is an ind icator for
the severity and location of the lesions. A liberal p olicy of p otential risk for inju ry to the feet and su bsequent d iabetic
coronary angiograp hy is reasonable becau se the cu rrent foot u lcers.
noninvasive tests are relatively insensitive. Also, the tech- Mental or em otional illnesses, inclu d ing neu roses and
niqu es of coronary angiography have changed in the p ast d ep ression, are com m on. Diagnosis and ap p ropriate treat-
few years, allow ing for selected arteriography w ith very m ent of these illnesses is an im p ortant p retransp lant con-
low -d ose, less toxic contrast agents u sing biplanar im aging sid eration w ith im portant im plications for ensuring a high
techniques. The nephrotoxic risk of angiography has been d egree of m ed ical com p liance.
red u ced consid erably, if a left ventriculogram is omitted , in
a preu remic p atient w ith creatinine clearance 20 mL/ min. ■ Deceased donor pancreas selection
Patients w ith coronary lesions am enable to angio-
and procurement
p lasty w ith stentin g or byp ass grafting sh ou ld be treated ,
re-evalu ated , and then reconsid ered for transp lantation. Id entification of su itable d eceased d onor organs for pan-
The goal of revascu larization is to d im inish the p eriop era- creas transp lantation is an im p ortant and often u nd erap -
tive risk of the transp lant p roced u re and to p rolong the p reciated d eterm inant of ou tcome. Misju d gm ent regard ing
d u ration of life p ost-transplant. Patients w ho have exp eri- the qu ality of the transp lantable organs m ay result in sig-
enced long w aiting p eriod s before pancreas transplanta- nificant ad verse consequ ences p ost-transp lant. The trans-
tion shou ld have their card iac statu s assessed at regu lar p lant op eration begins w ith organ procu rem ent.
intervals. In general, the criteria that d etermine an appropriate
Autonom ic neurop athy is prevalent and may m anifest d onor for pancreas transplantation are more stringent than
as neurogenic blad d er d ysfunction, gastropathy, and ortho- for kid ney or liver donors. Development of a pancreas d onor
static hyp otension. N eu rogenic blad d er d ysfunction is an risk index (PDRI) has been published that identifies factors
im portant consid eration in patients receiving a blad d er- associated w ith an increased risk of allograft failure in the
d rained , p ancreas-alone transplant or an SPK transp lant context of SPK transplant, PAK transplant, or PTA (18). Ten
(17). Inability to sense blad d er fu llness and to em p ty the d onor variables and one transplant factor (ischemia time)
blad d er p red isp oses to urine reflux and high p ostvoid have been combined into the PDRI. These DRIs includ e fac-
resid u als. These p roblem s m ay ad versely affect renal allo- tors that can be identified at the time of organ allocation that
graft fu nction, increase the incid ence of blad d er infections also pred ict the risk of early graft failure. Increased PDRI
and p yelonep hritis, and pred ispose to graft p ancreatitis. w as associated w ith a significant, graded reduction in 1-year
Im p aired gastric em ptying, gastroparesis, is an im p or- pancreas graft survival (Fig. 49.3). The cause of failure
tant consid eration w ith significant im p lications in the p ost- appeared similar across DRI categories for SPK transplant
transp lant p eriod . Patients w ith severe gastrop aresis m ay recipients. In the isolated pancreas transplant recipients
have d ifficu lty tolerating the oral im m unosu ppressive (PAK and PTA), however, there was a trend toward higher
med ications that are essential to prevent rejection of the rates of technical early loss among recipients of high DRI
transp lants. organs.
FIGURE 49.3. Adjusted 1-year graft survival following (A) simultane- 100%
ous kidney-pancreas (SPK) transplant, (B) pancreas after kidney (PAK)
95%
transplant, and (C) pancreas transplant alone (PTA), as a function of the
% Pancreas Graft
pancreas donor risk index (PDRI). 90%
Survival
85%
80%
75%
70%
65%
0 60 120 180 240 300 360
Time from Transplant (in Days)
DRI: 0.64–0.85 (N = 1,387) DRI: 0.86–1.15 (N = 1,906)
DRI: 1.16–1.56 (N = 1,135) DRI: 1.57–2.11 (N = 625)
A DRI: 2.12–2.86 (N = 218)
100%
% Pancreas Graft Survival

95%
90%
85%
80%
75%
70%
65%
0 60 120 180 240 300 360
DRI: 0.64–0.85 (N = 519) DRI: 0.86–1.15 (N = 764)
B DRI: 1.16–1.56 (N = 394) DRI: 1.57–2.11 (N = 167)
100%
% Pancreas Graft Survival
95%
90%
85%
80%
75%
70%
65%
0 60 120 180 240 300 360
DRI: 0.64–0.85 (N = 134) DRI: 0.86–1.15 (N = 250)
C DRI: 1.16–1.56 (N = 128) DRI: 1.57–2.11 (N = 79)
Deceased p ancreas organ d onors are typ ically betw een The bod y w eight of the d eceased organ d onor is an
the ages of 10 and 55. The low er age lim it d oes not relate to im p ortant consid eration. Obese d onors 100 kg are fre-
the m etabolic efficiency of the ped iatric end ocrine pancreas qu ently fou nd not to be su itable p ancreas d onors. Obese
to regu late blood su gar control in an ad ult. Rather, the p atients m ay have a history of typ e 2 d iabetes, or the p an-
low er age lim it of a p ed iatric d onor p ancreas reflects the creas m ay be fou n d to be u nsu itable for tran sp lan tation
anticip ated small size of the splenic artery, w hich m ay p re- becau se of a high d egree of ad ip ose in filtration of the
clu d e su ccessfu l constru ction of the arterial Y-graft need ed p ancreas.
for pancreas allograft revascularization. With respect to Donor hem od ynam ic stability and need for inotrop ic
u pper age lim its, the u se of pancreata from old er d onors su p p ort are im p ortant consid erations. H em od ynam ic sta-
has been associated w ith increased technical failu re d u e to bility has m ore influence on the anticipated function of the
pancreas graft throm bosis, a higher incid ence of post-trans- kid ney allograft than it d oes on initial end ocrine fu nction
plant p ancreatitis, and d ecreased pancreas graft su rvival of the p ancreas allograft in the case of an SPK transplant.
rates. Deceased d onors w ho have exp erienced a significant
period of card iac arrest or w ho require high d oses of p ro-

longed inotrop ic su pport frequ ently exhibit slow d eteriora-
tion of renal fu nction that m ay resu lt in d elayed renal
allograft fu nction in the SPK transp lant recipient.
The m ost im p ortant d eterm inant of su itability of the
p an creas for tran sp lan tation is d irect exam in ation of the
organ d u ring su rgical p rocu rem ent. The exp erience of
the p rocu rem ent team is im p ortant. Du ring p rocu rem ent
that ju d gm ent regard ing the d egree of fibrosis, ad ip ose
tissu e infiltration into the parenchym a, traum a, and sp e-
cific vascular anomalies can be mad e. Pancreata w ith heavy
infiltration of ad ipose tissu e are believed to be relatively
intolerant of cold preservation and the potential of a high
d egree of saponification d ue to reperfu sion pancreatitis fol-
low ing revascu larization. These organs may be m ore su it-
able for islet isolation.
The important vascular anomaly that must be evaluated
during procurement is the occurrence of a replaced or acces-
sory right hepatic artery originating from the superior
mesenteric artery (SMA). The presence of a replaced right
hepatic artery is no longer an absolute contraindication for
the use of the pancreas for transplantation. Experienced pro- FIGURE 49.4. Pancreaticoduodenal allograft with exocrine bladder drainage
and systemic venous drainage. (Adapted from Stuart FP, Abecassis MM,
curement teams w ill be able to successfully separate the liver Kaufman DB. Organ transplantation, 2nd ed. Georgetown: Landes Bioscience;
and the pancreas either in situ or on the backbench, w ithout 2003:166.)
sacrificing quality of either organ for transplantation.
A few im portant caveats d eterm ine w hether this
maneu ver is p ossible. The rep laced right hepatic artery beating d onors for p ancreas-alone transp lantation is a
mu st be d issected to the junction w ith the SMA. If the selective d ecision m ad e on a case-by-case basis.
rep laced right hep atic artery traverses d eep into the The u se of living related and u nrelated p ancreas d onors
parenchym a of the head of the pancreas, requ iring exten- has also been d escribed . A d istal p ancreatectom y is per-
sive d issection, this circum stance m ay preclu d e the p an- form ed for a segm ental p ancreas transp lant. Anecd otal
creas for transp lantation. The SMA is d ivid ed d istal to the cases of com bined live d onor partial pancreatectom y and
origin of the rep laced right hepatic artery, preserving intact nep hrectom y have also been rep orted . These p roced ures
a short length of SMA w ith a carrel patch for the liver graft. are not w id ely p erform ed and are confined to one or tw o
Occasionally, there is a large inferior pancreaticod u od enal p ancreas transp lant p rograms.
arterial branch vascularizing the head of the pancreas that
originates p roxim al to the origin of the rep laced right
hep atic artery. The inferior pancreaticod u od enal vessels
■ Pancreas transplantation surgery
are critical to vascularization of the head of the p ancreas The su rgical techniques for pancreas transplantation are
becau se the gastrod uod enal artery is routinely ligated d u r- d iverse (Figs. 49.4 to 49.6). The p rincip les are consistent,
ing the process of hepatic artery mobilization for the liver how ever, and inclu d e p rovid ing ad equ ate arterial blood
transp lant. In the case of a very proxim al origin of the infe- flow to the p ancreas and d u od enal segm ent, ad equ ate
rior p ancreaticod uod enal artery, d ivid ing the SMA at the venou s ou tflow from the p ancreas, and managem ent of the
app rop riate location for proper liver procu rem ent w ou ld p ancreatic exocrine secretions. The native p ancreas is not
significantly im p air vascularization of the head of the p an- removed .
creas and p reclu d e its use for transp lantation. Evalu ation Pancreas graft arterial revascu larization is typ ically
of the arterial vascu larity of the p ancreaticod u od enal allo- accom p lished u sing the recip ient right com m on or external
graft can be tested on the backbench by several m ethod s: iliac artery. The Y-graft of the p ancreas is anastomosed end
(a) injection of Renografin into the SMA or Y-graft and to sid e. Positioning of the head of the p ancreas graft cepha-
obtaining an x-ray; (b) intra-arterial injection of flu orescein, lad or cau d ad is not relevant w ith resp ect to su ccessfu l
w ith visu alization u sing a Wood lam p ; and (c) p erform ing arterial revascu larization. There are tw o choices for venou s
a m ethylene blu e angiogram . revascu larization—system ic and p ortal. System ic venou s
The u se of m arginal and nonheartbeating d onors for revascu larization com m only involves the right com m on
pancreas transp lantation has been reported . If the p ancreas iliac vein, or right external iliac vein. If p ortal venou s
is d eem ed su itable, there is the ad d ed consid eration of the d rainage is u sed , it is necessary to d issect the su p erior
effect of d elayed kid ney graft function in a urem ic SPK m esenteric vein at the root of the m esentery. The pancreas
transp lant cand id ate. The use of m arginal and nonheart- p ortal vein is anastom osed end to sid e to a branch of the
Donor Donor portal

Y-graft-internal vein-internal iliac
iliac artery vein anastomosis
anastomosis
FIGURE 49.6. Pancreaticoduodenal allograft with enteric exocrine

drainage and portal venous drainage. (Adapted from Stuart FP, Abecassis
MM, Kaufman DB. Organ transplantation, 2nd ed. Georgetown: Landes
Right common
iliac vein Bioscience; 2003:168.)
Right common
be hand led via anastom osis of the d u od enal segm ent to
iliac artery the blad d er or by anastom osis to the sm all intestine. The
blad d er-d rained p ancreas transp lant is a very im portant
m od ification that w as introd u ced abou t 1985. This tech-
nique significantly im proved the p roced u re’s safety by m in-
FIGURE 49.5. Pancreaticoduodenal allograft with enteric exocrine drainage im izing the occu rrence of intra-abd om inal abscess from
and systemic venous drainage. (Adapted from Stuart FP, Abecassis MM, leakage of enteric-d rained p ancreas grafts. With the suc-
Kaufman DB. Organ transplantation, 2nd ed. Georgetown: Landes Bioscience; cessful application of the new immunosuppressant agents
2003:167.)
and red u ction in the incid ence of rejection, enteric d rainage
of pancreas transplants has enjoyed a rebirth.
Enteric d rainage of the p ancreas allograft is p hysiologic
sup erior m esenteric vein. This anastom osis m ay influ ence w ith resp ect to the d elivery of p ancreatic enzym es and
the m ethod ology of arterial revascu larization u sing a long bicarbonate into the intestines for reabsorp tion. Enterically
Y-graft p laced throu gh a w ind ow in the m esentery to reach d rained p ancreases can be constru cted w ith or w ithou t a
the right com m on iliac artery. Portal venou s d rainage of the Rou x-en-Y intestinal lim b. The enteric anastom osis can be
pancreas is m ore p hysiologic w ith respect to im m ed iate m ad e sid e to sid e or end to sid e w ith the d u od enal segm ent
d elivery of insu lin to the recipient liver. Portal d rainage of the p ancreas. The anastom osis may be hand sew n or
resu lts in d im inished circu lating insu lin levels relative to accom p lished w ith the stap ler. The risk of intra-abd om inal
those in system ic venous-d rained pancreas grafts. The abscesses is extrem ely low (19), and the avoid ance of the
rou te of venou s d rainage has no d ocu m ented clinically rel- blad d er-d rained p ancreas has significant im p lications w ith
evant d ifferences in glycem ic control. resp ect to p otential com p lications that inclu d e blad d er
There are several m ethod s of m anaging the exocrine infection, cystitis, u rethritis, u rethral inju ry, balanitis,
d rainage of the p ancreas. Pancreatic exocrine d rainage m ay hematu ria, m etabolic acid osis, and the requ irem ent for
enteric conversion. Currently, approxim ately 75% of p an- Thrombosis

creas transp lants are perform ed w ith enteric d rainage, and Vascu lar th rom bosis is the m ost im p ortan t early com p li-
the rem aind er are p erform ed w ith blad d er d rainage. cation of p ancreatic transp lantation (20). Throm bosis can
The options of enteric versus bladder drainage d epend occu r at an y tim e p ost-tran sp lan t bu t typ ically occu rs
on the choice of venous d rainage and the clinical scenario of w ithin 48 h ou rs and u su ally w ithin 24 hou rs of the trans-
the pancreas transplant. For portally d rained pancreas trans- p lant. Throm bosis is generally d u e to venou s throm bosis
plants, bladder drainage is not an option. For SPK transplant of the tran sp lan t p an creas p ortal vein . The incid en ce is
recipients, enteric drainage is the technique of choice ap p roxim ately 5% to 8%. Arterial throm bosis is less com -
because there is no urinary monitoring benefit and the mor- m on and is u su ally associated w ith ath erosclerotic ves-
bidities as described earlier are significant. In the cases of sels. The etiology of throm bosis is not entirely d efined
PAK transplant and PTA, bladder drainage has two impor- bu t is believed to be associated w ith rep erfu sion p an cre-
tant ad vantages: (a) urinary monitoring for rejection and (b) atitis, the relatively low -flow state of the p ancreas graft,
placement of the graft, allow ing access for percutaneous and u nrecognized concom itant p rothrom botic d isord ers.
biopsy for d iagnosis of rejection. In the latter situation, the The qu ality of the p ancreas graft, the age of the d onor,
advantages of monitoring outweigh the morbidities associ- and the cold ischem ia tim e also influ ence graft throm bo-
ated with bladder drainage, at least in the short term, w hen sis rates.
the risk of imm unologic graft loss is significant. Acu te ven ou s throm bosis is h erald ed by a su d d en rise
The p ancreas is typ ically d rained into the blad d er if a in seru m glu cose, p ain d irectly over th e p ancreatic graft,
PTA or PAK transplant is perform ed in ord er to u se m eas- and , occasionally, ip silateral low er extrem ity sw elling
urem ent of u rinary am ylase as a m ethod of d etecting rejec- from extension of th e th rom bu s in to th e com m on iliac
tion. H ow ever, some p rogram s have had good exp erience vein.
w ith enteric d rainage of the PTA, u sing other m arkers for Confirm atory noninvasive d iagnostics m ay be help fu l
rejections, su ch as clinical signs and sym ptom s of p ancreas w hen the clinical p ictu re is not consistent w ith loss of
graft pancreatitis and seru m am ylase or lipase levels cou- p ancreas graft viability. Perfu sion im aging of the graft
pled w ith biop sy. u sing technetiu m -99m hexam ethylp rop ylene am ine oxim e
(H MPAO) m ay reveal loss of p ancreas graft p erfu sion and
■ Complications in the postoperative setting a p hotop enic region (21). Figu re 49.7 illu strates a norm al
p erfu sion scan of the p ancreas and kid ney grafts of an SPK
Table 49.2 ou tlines the m ost com m on com plications in the transp lant recip ient and an abnorm al scan w herein the
early postoperative period . p ancreas allograft is not p erfu sed . Ultrasonograp hy is
often u sed to d eterm ine the qu ality of vascu lar flow to and
Table 4 9 .2 Pot en t ia l ea r ly com p lica t ion s of from the p ancreaticod u od enal allograft. Ultrasonograp hy
p a n cr ea t ic t ra n sp la n t a t ion ad vantages inclu d e the p ortable natu re of the scanning
d evice, bu t the qu ality of resu lts is highly d ep end ent on
Thrombosis the skills of the technician and rad iologist. Com p u ted
Arterial tom ography (CT) is usually not the d iagnostic test of choice
Venous bu t m ay reveal find ings consistent w ith p ancreas allograft
Hemorrhage throm bosis that inclu d e an enlarged and inhom ogeneou s
Pancreatic graft p ancreas graft (Fig. 49.8).
Vascular anastomosis
Infection
Bacterial or fungal
Peripancreatic fluid
Superficial wound
Urinary tract
Metabolic
Acidosis
Hyperkalemia, hypokalemia, hypocalcemia, and hypomagnesemia
Dehydration
Gastrointestinal
Anastomotic leak (enteric-drained graft)
Mechanical obstruction A B
Urologic FIGURE 49.7. Technetium-99 m hexamethyl propylene amine oxime (99mTc-

Hematuria HMPAO) radionucleotide scintigraphic scan of a well-perfused simultaneous
Bladder anastomotic leak (bladder-drained graft) pancreas-kidney (SPK) transplant recipient (A) and of an SPK transplant
Urethral injury/stenosis recipient with acute thrombosis of the pancreaticoduodenal allograft
(B). Images were recorded 0 to 5 minutes after labeled contrast injection.
Anticoagulation therapy is routinely used to reduce the

incid ence of pancreatic graft thrombosis. Although there is
no stand ard protocol for optimal anticoagulation regimen
early post-transplant, most centers employ a combination
approach involving a heparin agent and an antiplatelet
agent such as aspirin. The concern with instituting anticoag-
ulation therapy is the increased risk of postoperative hemor-
rhage. Although the thrombosis/ hemorrhage d ichotomy
complicates postoperative patient care, the m anagement of
mild postoperative bleed ing is more acceptable than the irre-
versible consequences of allograft thrombosis.
Hemorrhage
This complication is common w henever any major vascular
proced ure is p erformed . The use of postoperative anticoag-
FIGURE 49.8. Computed tomographic image of pancreas graft thrombosis ulation to d iminish the frequency of allograft thrombosis
showing an enlarged and inhomogeneous graft. (Reprinted from Letourneau
J G, Day DL, Ascher NL. Radiology of organ transplantation. St Louis: Mosby,
increases the risk of this com p lication. Bleed ing from the
1991:269, with permission.) vascular anastomotic site and ligatures or cut surfaces of the
pancreatic graft w ill result in an intra-abd ominal accu mula-
tion of hematoma. Clinical suspicion, physical examination,
Managem ent of p ancreatic graft throm bosis requ ires serial blood counts, and attention to abd om inal d rain efflu-
u rgent op erative intervention—either throm bectom y and ents often reveal postop erative hem orrhage. Frequ ently,
vascu lar revision or graft excision. The find ings at su rgery d iscontinuation of anticoagulants/ antiplatelet agents, cor-
u sually reveal an ischem ic, d usky, and nonviable p ancreas rection of coagulation abnormalities by ad ministration of
and d u od enal segm ent, w ith fresh clot in the graft p ortal platelets, vasopressin, vitamin K, fresh-frozen plasma, cryo-
vein (Fig. 49.9). Salvage of the throm bosed graft is not to be precipitate, and so on, and medical support is all the therapy
expected , bu t anecd otal salvage has been d escribed (22). that is required. Aggressive resuscitative efforts and opera-
Fortu nately, as a result of ad vances in cold p reservation, tive intervention consisting of celiotomy w ith evacuation of
technical m od ifications, and w id espread u se of postop era- hem atom a and control of hem orrhage are essential if hem o-
tive anticoagu lation, this is a com plication of d ecreasing d ynam ic instability d evelop s. The intraop erative find ings
incid ence. reveal fresh and clotted hem atom a, often w ithou t a d efini-
tive bleed ing sou rce (Fig. 49.10). The hem atom a is w ashed
ou t, exp loration for a sou rce of bleed ing is cond ucted ,
Donor portal vein
Right common
iliac vein
Right common
iliac artery
Thrombus
Donor Y-graft
FIGURE 49.9. Intraoperative vignette of the surgical findings of acute pan- FIGURE 49.10. Intraoperative vignette of the surgical findings of acute
creatic graft thrombosis. intra-abdominal hemorrhage in a pancreatic graft recipient.
coagulopathy is corrected, and the viability of the pancreas mately 500 cc of richly bicarbonate fluid w ith pancreatic
(and kidney) is confirmed. Gastrointestinal (GI) bleeding enzym es into the blad d er each d ay. Change in pH of the
may occur from the enteric-drained pancreas from a combi- blad d er accou nts, in p art, for an increase in u rinary tract
nation of perioperative anticoagulation and bleeding from infections. In som e cases, a foreign bod y, su ch as an exposed
the suture line of the duodenoenteric anastomosis (23). suture from the d uod enocystostomy, acts as a nid us for uri-
Suture line bleeding is self-limited and w ill manifest as nary tract infections or stone form ation. Acute postopera-
diminished hemoglobin level associated w ith heme-positive tive hematuria of the blad d er-d rained pancreas is usually
or melanotic stool. Conservative management is appropriate; d ue to ischemia/ reperfusion injury to the d uod enal mucosa
reoperative exploration is unusual. or to a bleed ing vessel on the suture line that is aggravated
by antiplatelet or anticoagu lation protocols to minimize
Transplant Pancreatitis vascular thrombosis. Small amounts of hematuria require
Pancreatitis of the allograft occurs to some degree in all only close observation, but larger clots may need continu-
patients postoperatively. A temporary elevation in serum ous blad d er irrigation or d irect cystoscopic evaluation and
amylase levels is common for 48 to 96 hours post-transplant. cautery. Occasionally, it is necessary to perform a form al
Most episod es are transient and mild w ithout significant open cystotomy w ith suture ligation of the bleed ing vessel
clinical consequence. It is comm on for SPK transplant recipi- intraop eratively.
ents to have a greater degree of fluid retention for several Sterile cystitis, u rethritis, and balanitis m ay occu r after
days post-transplant, com pared with kidney-transplant- blad d er-d rained p ancreas transp lantation d u e to the effect
alone recipients. Though not proven, fluid retention may be of the p ancreatic enzym es on u rinary tract m u cosa. Cystitis
related to graft pancreatitis that ensues in the perioperative is m ore com m on in m ale recip ients. Urethritis can p rogress
period. The retained fluid is mobilized early postoperatively. to u rethral p erforation and p erineal p ain. Conservative
It is important to minimize the risk of d elayed kid ney graft treatm ent w ith catheterization and op erative enteric con-
function by shortening cold ischemia time so that the version are the extrem es of the continu u m of treatm ent.
retained third-space fluid may be rapidly eliminated to Metabolic/ flu id / electrolyte com p lications m ay be
avoid an episode of heart failure or pulmonary edema. exacerbated by the p roced ure of pancreatic exocrine blad -
d er d rainage. Metabolic acid osis rou tinely d evelops as a
Complications Associated with Bladder Drainage consequence of blad d er excretion of large quantities of the
of Pancreatic Exocrine Secretions
alkaline p ancreatic secretions. Patients mu st receive oral
Many mild to m od erately severe complications arise bicarbonate su p p lem entation to m inim ize the d egree of
because of the u nu sual physiologic consequ ences of d rain- acid osis. Blad d er-d rained p ancreas recip ients m ay have
ing p ancreatic exocrine secretions into the blad d er (24) d ifficu lty com p ensating for the ad d ed flu id losses. Som e
(Fig. 49.11). The pancreas transplant eliminates approxi- im m u nosu p p ressive agents (e.g., m ycop henolate m ofetil)
ind u ce low er gastrointestinal d ysfu nction, resulting in
increased bow el activity of a w atery natu re that m ay exac-
erbate the propensity for d ehyd ration in the patient w ith a
blad d er-d rained p ancreas allograft. Carefu l m onitoring of
seru m electrolytes and acid –base balance is necessary. Elec-
trolyte and flu id rep letion m ay be necessary to avoid d ehy-
d ration. Patients shou ld be started on flu id and bicarbonate
su p p lem entation early and ed u cated abou t this entity
before d ischarge in ord er to p revent severe d ehyd ration
and p ossible graft loss.
Reflux pancreatitis Reflu x p ancreatitis can resu lt in acu te in flam m ation of
the p ancreas graft, m im icking acu te rejection. Reflu x
p an creatitis is associated w ith p ain an d h yp eram y-
Anstomotic
lasem ia and is believed to be second ary to reflu x of u rine
leak throu gh the am p u lla an d in to th e p ancreatic d u cts. Often
Cystitis the u rine is contam inated w ith bacteria. Bacterial con-
Hematuria Urinary tract innection
tam ination occu rs in p atients w ith neu rogenic blad d er
d ysfu nction . Th is com p lication is m anaged acu tely by
Urethritis Foley catheterization. The p atient m ay requ ire a com -
Urolithiasis
p lete w orku p of th e cau se of blad d er d ysfu nction , in clu d -
ing a p ressu re flow stu d y and void ing cystou rethrogram .
In old er m ale p atien ts, even m ild h yp ertrop hy of the
p rostate h as been d escribed as a cau se of reflu x p ancreati-
FIGURE 49.11. Postoperative complications associated with the bladder- tis. If recu rrent graft p ancreatitis occu rs, enteric conver-
drained pancreas transplant. sion m ay be ind icated .
Urine leak from breakd ow n of the d u od enal segm ent

can occu r and is u su ally encou ntered w ithin the first 2 to
3 m onths p ost-transp lant, bu t it can occu r years p ostop er-
atively. Leak is the m ost seriou s p ostop erative com p lica-
tion of the blad d er-d rained p an creas. The on set of
abd om inal p ain w ith elevated seru m am ylase, w hich can
m im ic reflu x p ancreatitis or acu te rejection, is a typ ical
p resentation. Su p p orting im aging stu d ies u tilizing a cys-
togram or CT scanning are necessary to confirm the d iag-
nosis. Op erative rep air is u su ally requ ired . The d egree of
leakage can be best d eterm ined intraop eratively and
p rop er ju d gm ent m ad e abou t w hether d irect rep air is p os-
sible or m ore aggressive su rgery involving enteric d iver-
sion (25) (Fig. 49.12) is ind icated .
FIGURE 49.13. Computed tomographic study of a well-marginated, low-

density fluid collection anterior to the pancreas transplant (arrows).
(Reprinted from Letourneau J G, Day DL, Ascher NL. Radiology of organ trans-
plantation. St Louis: Mosby, 1991:278, with permission.)
Infection
The m ost seriou s com p lication of p ancreas transp lantation
is leak and intra-abd om inal abscess. Patients p resent w ith
fever, abd om inal d iscom fort, and leu kocytosis. Com pu ted
tom ograp hic stu d y of the abd om en is help fu l to confirm
clinical su spicion and to localize infected p erip ancreatic
flu id collections (Fig. 49.13). Du od enoenteric anastomotic
leak occu rs as a resu lt of an ischem ic d u od enal stu m p, tech-
nical error, or d u od enal stu m p blow ou t. Percutaneou s
access of intra-abd om inal flu id collections for Gram stain
and cu ltu re is essential. The flora is typ ically m ixed w ith
bacteria and p ossibly fu ngu s (26), p articu larly Candida.
Broad -sp ectru m antibiosis is essential. Su rgical exp loration
is required if conservative m ethod s of percu taneous
d rainage d o not ad equ ately control established infection.
Intraop erative find ings u su ally reveal fibrinou s ad he-
sive d isease w ith interloop abscess. Exp loration and rep air
of a d u od enal graft leak is necessary. A d ecision m u st be
m ad e on w hether the infection can be erad icated w ithou t
rem oving the p ancreas allograft. Incom p lete erad ication of
the infection w ill resu lt in p rogression to sep sis and m u lti-
Reanastomosis on the p le organ system failu re. Perip ancreatic infections can
anti-mesenteric border resu lt in d evelop m ent of a m ycotic aneu rysm at the arte-
of the mid-jejunum
rial anastom osis that cou ld cau se arterial ru p tu re. Trans-
p lant p ancreatectom y is ind icated if m ycotic aneu rysm is
d iagnosed .
The occu rrence of intra-abd om inal abscess has been
greatly red u ced w ith greater recognition of the su itability
of cad averic p ancreas grafts for transp lantation.
Im p roved p eriop erative antibiosis, inclu d ing antifu ngal
agents, has contribu ted to the d ecreased incid ence of
intra-abd om inal infection as w ell. There is no convincing
evid ence that a Rou x-en-Y intestinal reconstru ction
d ecreases incid ence. Perhap s the m ost significant contri-
FIGURE 49.12. Surgical procedure of enteric conversion of the bladder- bu tion to red u cing intra-abd om inal abscesses is the effi-
drained pancreaticoduodenal transplant. cacy of the im m u nosu p p ressive agents in red u cing acu te
rejection and thereby m inim izing the need for intensive abd om en rarely occu rs bu t can be cau sed by rejection-
antirejection im m u notherap y. ind u ced p ancreatitis. Inflam m ation of the su rrou nd ing
The most im portant threat to loss of a functioning pan- organs, su ch as the sm all an d large in testine, m ay resu lt
creas allograft is acute rejection. The graft’s fate is intimately in a d ynam ic ileu s or d iarrhea, resp ectively.
linked to the efficacy and safety of im m u nosu pp ressive Laboratory m arkers are com m only relied on to gu id e
agents and the recipient’s med ical comp liance. Throu gh su bsequ ent im aging stu d ies or biop sy. Profou nd d estru c-
jud icious application of im munosuppression, both rejection tion of exocrine p ancreatic tissu e occu rs before significant
and infectiou s com plications m ay be avoid ed . Pancreatic d eterioration in end ocrine p ancreatic fu nction (32). H yper-
allograft m onitoring to d iagnose acu te rejection in a tim ely glycem ia is a late parameter of rejection and is usually
manner is essential to achieve long-term survival. Overtreat- ap p arent only after extensive d estru ction of the islets has
ment of a suspected rejection episode can be a serious cause taken p lace. H yp erglycem ia is not u sefu l to d iagnose acute
of infectious morbid ity and mortality in pancreas transplant rejection that is likely to be reversed . H yp erglycem ia is also
recipients. a sign of d evelop ment of p erip heral insu lin resistance (type
Pancreas allograft rejection can be characterized as 2 d iabetes). Differentiation of loss of cell insu lin p rod u c-
hyp eracu te, acu te, an d chronic. H yp eracu te rejection tion (rejection) is accom p lished by m easu rem ent of
occu rs m inu tes to hou rs follow ing revascu larization of C-p ep tid e levels. Using p ancreas-sp ecific seru m m arkers
the p ancreas graft. H yp eracu te rejection occu rs w hen to d etect rejection is p roblem atic d u e to the p athop hysiol-
p reform ed anti-H LA (H istocom p atibility Leu kocyte Anti- ogy of the exocrine p ancreas. Rejection, as w ell as p ancre-
gens) antibod ies bind to graft end otheliu m , activate the atitis, infection, or p reservation inju ry, lead s to d am age of
com p lim ent cascad e, and prod u ce capillary m icrothrom bi. acinar tissu e, w ith su bsequ ent enzym e and cytokine
H yp eracute rejection is rare if the pretransp lant screening release. The cau ses of d estru ction of p ancreas acinar tissue
crossm atch is nonreactive. This form of rejection can be a are m u ltip le and , w ith p ancreas-sp ecific seru m param eters
d ifficu lt d iagnosis because of the relatively high incid ence only, d ifficu lt to d ifferentiate.
of early organ failure d u e to vascu lar throm bosis. The few An increase in serum amylase usually occurs w ith rejec-
cases p ublished d escribe negative crossm atches in recipi- tion and preced es a d ecline in urinary amylase (in recipients
ents w ith high p anel-reactive antibod y levels (27). w ith blad d er-d rained pancreas) (33,34). Post-transplant
Acu te p ancreatic graft rejection typically occu rs 3 to 12 hyperamylasemia can be caused by any process ind ucing
months post-transplant bu t can hap pen later if med ical pancreatic inflammation. In add ition, serum amylase is also
noncomp liance occurs. Acu te rejection is prim arily a fu nc- d erived in large part from other tissues, including salivary
tion of cell-m ed iated cytotoxicity. The initial cellu lar targets gland s and intestine. Several stud ies on SPK transplant
of rejection are end othelial cells, acinar, and d u ctal ep ithe- recipients show ed elevated human anodal trypsinogen
lial cells. Islets and cells are not p rimary targets of allo- (H AT) levels d uring clinically d iagnosed rejection episod es
im m u ne rejection (27). Islets m ay be involved late in (35). H AT levels are frequently elevated in the early post-
rejection and m ay also stop fu nctioning before becom ing transplant period , w hich may reflect preservation or pro-
involved w ith inflam m atory cells (28,29). curement injury rather than rejection. Renal d ysfunction,
Chronic rejection is a m ore ind olent process that occu rs pancreatitis, trauma, and bladd er outlet obstruction may
relatively late in the cou rse of transp lantation. The m ost also influence HAT levels. One study performed on SPK and
notable contribu ting factor includ es m ultiple acute rejec- PAK transplant recipients includ ed both renal biopsies and
tion ep isod es (30). Chronic rejection in the pancreas is char- H AT levels, find ing H AT as a reliable marker of pancreas
acterized by arterial narrow ing and interstitial fibrosis w ith rejection in all cases (36).
variable loss of acinar and islet tissue (29,31). Arteriop athy In the context of SPK transp lantation, the kid ney allo-
cau ses progressive ischem ic d am age to the acinar and islet graft is the best ind icator of a rejection ep isod e. Rejection of
tissu es, resu lting in extensive pancreatic fibrosis. the kid ney allograft w ill m anifest as a rise in seru m creati-
nine. Increased seru m creatinine w ill p romp t u ltrasound
and biop sy of the kid ney allograft, and if rejection is d iag-
■ Diagnosis nosed , antirejection therap y is institu ted . If there is a con-
The clinical p resentation of pancreas allograft rejection can cu rrent p ancreas graft rejection p rocess, the antirejection
be su btle. Only 5% to 20% of p atients w ith p ancreatic graft therap y w ill reverse the p rocess in both organs.
rejection p resent w ith obviou s clinical sym ptom s. The p an- Blad d er d rainage is a w id ely used technique for manage-
creatic graft und ergoing acute rejection becom es inflam ed . ment of exocrine secretion in pancreatic transplantation
Patients exp erience p ain and d iscom fort d u e to su rrou nd - because it also allows graft exocrine function to be moni-
ing p eritoneal irritation, but rejection is d ifficult to d istin- tored by measuring pancreatic enzymes secreted d irectly
gu ish clinically from benign graft pancreatitis. Fever as a into the urine (37). Bladder drainage is mostly used in recip-
clinical sym p tom of rejection is u ncom m on, partly d u e to ients of PAK transplant and PTA. The technique is becoming
maintenance im m u nosup pressive therapy w ith pred - less frequently used in SPK transplant recipients because
nisone. If the w orku p for infection is negative, fever is monitoring renal allograft function serves as a better indica-
highly su sp iciou s for rejection. A p aralytic ileu s or acu te tion of rejection (and a surrogate marker of pancreas graft
rejection) and there is less morbidity w ith enteric drainage. su p p ression. The p rincip les of im m u nosu p p ressive ther-
Serial urine amylase measurement has emerged as a very ap y for p ancreas recip ients are sim ilar to those ap p lied to
common surveillance and d iagnostic laboratory test. A recip ients of other solid -organ allografts. The ad vent of
reduction in urinary amylase activity, relative hypoamyla- m ore effective im m u nom od u lating agents has red u ced the
suria, is the most commonly used biochem ical marker of frequ ency and severity of p ancreatic allograft rejection
acute rejection in the PAK transplant and PTA recipient cate- ep isod es. H ow ever, acu te rejection continu es to be the
gories. By monitoring urinary amylase levels, antirejection m ost challenging event in the cou rse of p ancreatic graft
treatment can begin before hyperglycemia occurs. Urinary recip ients.
amylase measurements are simple, without morbid ity, and The u se of ind u ction therap y has been show n to signif-
relatively inexpensive, and most laboratories can perform icantly im p rove p ancreas graft su rvival rates in several
them. One of the limitations of urinary am ylase m onitoring su bgrou p s. Accord ing to d ata from the IPTR, the u se
is that a decrease in activity does not necessarily mean rejec- of ind u ction therap y in SPK transp lant recip ients w ith
tion. Red uced urinary amylase levels m ay be caused by system ic venou s–enteric exocrine d rainage significantly
other factors, such as preservation injury in the early post- im p roves p ancreas graft su rvival rates (40,41). Interest-
transplant period , pancreatitis, fibrosis, thrombosis, d uctal ingly, p ancreas graft su rvival is not im p roved w ith ind u c-
obstruction, prolonged fasting, hyd ration status, and d iure- tion therap y in the su bgrou p s w ith p ortal venou s-enteric or
sis (38). blad d er d rainage. Fu rtherm ore, SPK transp lant recipients
Core N eed le biopsy is the stand ard for the d iagnosis of w ho receive ind u ction therap y benefit from a red u ced inci-
pancreas allograft rejection in the context of PAK trans- d ence and severity of biop sy-confirm ed , treated , acu te kid -
plant and PTA. For m ost solid organ transplants, histologic ney rejection ep isod es. For solitary p ancreas transplant
evaluation of graft biopsies becam e the stand ard assess- recip ients (PAK and PTA), the ad d ition of ind u ction ther-
ment for rejection early on. For pancreas transplantation, ap y is associated w ith a clinically significant im p rovem ent
the d evelop m ent w as d ifferent for tw o reasons. It is rare in p ancreas graft su rvival rates.
that isolated p ancreatic rejection occu rs in SPK transp lant Maintenance im m u nosu p p ressive agents u sed for p an-
recipients w ithou t sim ultaneous renal allograft rejection. In creas transplantation fall into the follow ing categories: (a)
these p atients, m ost rejection ep isod es involve either the corticosteroids, (b) calcineurin inhibitors (cyclosporine and
kid ney alone or the kid ney and the pancreas sim ultane- tacrolim us), (c) antimetabolites (azathioprine and m ycophe-
ously (39). This observation has prom oted the percep tion nolate m ofetil), and (d ) cell cycle inhibitors (sirolimus). In
that p ancreatic graft rejection can be m onitored ind irectly 2002, solitary pancreas transplant recipients received corti-
by relying on seru m creatinine changes or kid ney graft costeroid s in ap p roxim ately 90% of cases, tacrolim us in
biopsies. For SPK transplants, the kid ney serves as an 91% (cyclosp orine 8%), m ycop henolate m ofetil in 70%
excellent su rrogate m arker for rejection. In solitary p an- (azathiop rine 1%), and sirolim u s in 18%. Therefore, in 2002,
creas transp lant recip ients (PAK and PTA), seru m creati- the m ost frequ ently u sed com bination of m aintenance ther-
nine levels or kid ney biopsies cannot be u sed as m arkers of ap y at d ischarge w as tacrolimus, mycophenolate mofetil,
rejection, and , given the inad equacies of laboratory p aram - and corticosteroids.
eters, biop sies are therefore essential for m onitoring soli- Trend s in the uses of maintenance therapies over the
tary p ancreas transplants. In SPK transplant recip ients, past 10 years for solitary pancreas transplant recipients
isolated pancreatic graft rejection can occur and pancreatic (PAK and PTA) are d epicted in Figu re 49.14. The d ominant
graft biopsies m ay becom e necessary if a change in use of tacrolimu s tod ay represents a marked shift from ear-
exocrine or end ocrine laboratory param eters occu rs w ith- lier eras. The U.S. Food and Dru g Ad m inistration (FDA)
ou t an elevation in seru m creatinine. approved tacrolimu s for marketing for kid ney transplanta-
Cu rrently, the vast m ajority of pancreatic graft biop sies tion in 1994. In 1993, cyclosp orine accou nted for virtually
are obtained either p ercutaneou sly or cystoscopically and 100% of the calcineurin inhibitor use in pancreas transplan-
only rarely by lap arotom y or laparoscopy. Most centers tation. Since that time, tacrolimus use has increased yearly
prefer u ltrasou nd -gu id ed , percu taneous biopsy, perform ed and reached 91% in 2002. The FDA app roved mycopheno-
und er local anesthesia. If it is im possible to obtain tissu e for late m ofetil for m arketing for kid ney transp lantation in
histology or if overlying bow el prohibits sam pling, the cys- 1995, and it w as u sed in only 14% of solitary pancreas trans-
toscop ic ap p roach is em p loyed for blad d er-d rained grafts. plant cases that year (azathioprine w as u sed in 72% of
Lap arotom y or laparoscopy and biopsy are reserved for cases). H ow ever, w ithin 1 year, nearly 80% of solitary pan-
grafts inaccessible by the aforem entioned approaches creas transplant recipients received mycophenolate mofetil,
w hen the risks of em p iric antirejection therap y ou tw eigh w ith only 12% receiving azathioprine. The use of azathio-
those of su rgery. prine has d iminished yearly and d ropped to 1% usage in
2002. In 1999, the FDA ap p roved the u se of sirolim us for
m arketing for kid ney transp lantation. For p ancreas trans-
■ Immunosuppression plantation, this agent is u su ally u sed in com bination w ith a
Over the p ast d ecad e, p ancreas transp lantation resu lts calcineurin inhibitor and as a substitute for an antimetabo-
have im p roved significantly d u e to ad vances in im m u no- lite. The use of sirolimus has been relatively slow to penetrate
100
Cyclosporine Tacrolimus
FIGURE49.14. Trends in maintenance immuno-
suppression in recipients of solitary pancreas
80 transplants. (Adapted from 2005 OPTN/SRTR
Patients (%)
Annual Report.)
60
40
20
0
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002
Year
Azathioprine Mycophenolate mofetil Sirolimus

100
80
Patients (%)
60
40
20
0
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002
Year
the market, compared w ith the rapid spread of tacrolimus 55% in 1995 to 85% in 2004. Cyclosp orine usage has
and mycop henolate mofetil. In 2002, sirolimus w as used for d rop p ed from 35% of cases in 1994 to only 10% of cases in
18% of solitary pancreas transplant cases. 2004. Sim ilar trend s in the u se of antim etabolites are seen
Sim ilar trend s in m aintenance im m u nosu p p ression w ith resp ect to azathiop rine and m ycop henolate m ofetil. In
w ere also observed for SPK transplant recipients. The 1995, azathiop rine w as u sed in 60% of cases, d ropping to
changes in uses of specific m aintenance im m unotherapies 1% in 2004; m ycop henolate m ofetil u sage grew from 25% in
over the p ast 10 years for SPK transp lant recip ients are 1995 to 80% in 2004. From 2000 to 2004, sirolim us u sage
d ep icted in Figu re 49.15. The u se of tacrolim u s rose from rose from 12% to 20% of cases.
100 FIGURE 49.15. Trends in maintenance

Cyclosporine Tacrolimus immunosuppression in recipients of simultane-
80 ous pancreas-kidney transplants. (Adapted from
2005 OPTN/SRTR Annual Report.)
Patients (%)
60
40
20
0
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002
Year
100 Azathioprine Mycophenolate mofetil Sirolimus
80
Patients (%)
60
40
20
0
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002
Year
■ IMMUNOLOGICAL PROGRESS IN combined with technical refinements will make pancreatic

transplantation a safer and more w id ely applied treatment
PANCREATIC TRANSPLANTATION
option for patients with diabetes.
Changes in clinical practice patterns regard ing the u se of
the m aintenance im m u nosu p p ressive agents have had a
significant beneficial effect on ou tcom es of p ancreas trans- ■ REFERENCES
plantation (40). Pancreas transplant resu lts have stead ily
1. Portuese E, Orchard T. Mortality in insu lin-d ep end ent d iabetes. In:
im proved . Accord ing to the SRTR and the IPTR, over the H arris MI, Cow ie CC, Stern MP, Boyko EJ, Reiber GE, Bennett PH , ed s.
10-year p eriod from 1995 to 2004, p ancreas graft fu nctional Diabetes in America. Washington, DC: US Governm ent Printing Office;
su rvival (enteric d rainage) in SPK transp lant recip ients has 1995:221–232.
2. N ational Diabetes Data Grou p , N ational Institu tes of H ealth. Diabetes
increased from 76% to 86% (42). For PAK transplantation, in America, 2nd ed . Bethesd a, MD: N ational Institu tes of H ealth; 1995.
pancreas graft fu nctional survival (enteric d rainage) has N IH Pu blication N o. 95-1468.
show n stead y im p rovem ent over the 10-year interval from 3. Epid em iology of Diabetes Interventions and Com p lications (EDIC)
Research Grou p . Effect of intensive d iabetes treatm ent on carotid
1995 to 2004 from a 1-year patient su rvival rate of 67% to artery w all thickness in the epid em iology of d iabetes interventions and
77%. For p atients receiving a PTA, the pancreas graft fu nc- com p lications. Diabetes 1999;48:383–390.
tional su rvival (enteric d rainage) rates over the past 10 4. DCCT/ EDIC Research Grou p . Effect of intensive therap y on the
m icrovascular complications of type 1 diabetes mellitus. JAMA 2002;287:
years has im p roved from 67% to 84%. The p eriod 1995 2563–2569.
reflects u se of tod ay’s “second -line” im m u nosu p p ressants 5. Morel P, Goetz F, Mou d ry-Mu nns KC, et al. Long term m etabolic con-
(cyclosp orine and azath iop rine), w h ereas 2004 reflects trol in p atients w ith pancreatic transp lants. Ann Intern Med 1991;115:
694–699.
the p eriod of m atu re integration of the new “first-line” 6. N avarro X, Kenned y WR, Loew enson RB, et al. Influ ence of p ancreas
im m u nosu p p ressive agents (tacrolim u s, m ycop henolate, transplantation on card ioresp iratory reflexes, nerve cond u ction, and
an d sirolim u s) in to m ainstream u se. In ad d ition to graft m ortality in d iabetes m ellitu s. Diabetes 1990;39:802–806.
7. Kenned y WR, N avarro X, Goetz FC, et al. Effects of p ancreatic trans-
su rvival im p rovem ents, there have been su bstantial plantation on d iabetic neu ropathy. N Engl J Med 1990;322:1031–1037.
im p rovem ents in controlling the risk of graft rejection. 8. Fioretto P, Mau er SM, Bilou s RW, et al. Effects of p ancreas transp lanta-
Figu re 49.16 show s 1-year rejection rates accord ing to tion on glom erular stru cture in insulin-d ep end ent d iabetic patients
w ith their ow n kid neys. Lancet 1993;342:1193–1196.
transp lant era. Rejection rates d ecreased from 59% to 20% 9. Bilou s RW, Mau er SM, Su therland DE, et al. The effects of p ancreas
in SPK transp lant recip ients and d ecreased from 56% to transplantation on the glom eru lar stru ctu re of renal allografts in
23% in solitary p ancreas transp lant recip ients. patients w ith insulin-d ep end ent d iabetes. N Engl J Med 1989;321:80–85.
10. Zehr PS, Mild e FK, H art LK, et al. Pancreas transp lantation: assessing
Aggregate outcome information from national d atabases second ary com p lications and life qu ality. Diabetologia 1991;34(Su p p l 1):
and single-center reports (43) also demonstrate that improve- S138–S140.
m ents in the technical and im m u nologic ap p roaches to 11. Ojo AO, Meier-Kriesche H U, H anson JA, et al. Im p act of sim u ltaneou s
pancreas–kid ney transp lantation on long-term p atient su rvival. Trans-
pancreatic transp lantation h ave m oved the field forw ard . plantation 2001;71:82–90.
H ow ever, fu rth er refin em en ts are need ed to d ecrease 12. Mohan P, Safi K, Little DM, et al. Im p roved p atient su rvival in recip i-
com p lication rates. Continued advances in immunotherapy ents of sim ultaneou s p ancreas–kid ney transp lant com p ared w ith kid -
ney transp lant alone in p atients w ith typ e 1 d iabetes m ellitu s and
end -stage renal d isease. Br J Surg 2003;90:1137–1141.
60 13. Clarke WL, Cox DJ, Gond er-Fred erick LA, et al. Red u ced aw areness of
Pancreas alone hyp oglycem ia in ad u lts w ith IDDM. A p rosp ective stu d y of hyp o-
Simultaneous pancreas-kidney glycem ic frequ ency and associated sym p tom s. Diabetes Care 1995;18:
50 517–522.
14. Kroslew ski AS, Kosinski EJ, Warram JH , et al. Magnitu d e and d eterm i-
Rejection incidence (%)
nants of coronary artery d isease in ju venile-onset, insu lin-d ep end ent

d iabetes m ellitu s. Am J Cardiol 1987;59:750–755.
40 15. Borch-Johnsen K, Kreiner S. Proteinu ria: valu e as p red ictor of card io-
vascular m ortality in insu lin d ep end ent d iabetes m ellitu s. Br Med J
1987;294:1651–1654.
30 16. Gru nd y SM, Benjam in IJ, Bu rke GL, et al. Diabetes and card iovascu lar
d isease: a statem ent for healthcare p rofessionals from the Am erican
H eart Association. Circulation 1999;100:1134–1146.
20 17. Blanchet P, Drou py S, Eschw ege P, et al. Urod ynam ic testing p red icts
long-term u rological com plications follow ing sim u ltaneou s pan-
creas–kid ney transp lantation. Clin Transplant 2003;17:26–31.
10 18. Axelrod D, Su ng R, Meyer KH , et al. System atic evalu ation of p ancreas
allograft qu ality, outcom es, and geograp hic variation in u tilization. Am
J Transplant 2010;10:837–845.
19. Pirsch JD, Od orico JS, D’Alessand ro AM, et al. Intra-abd om inal infec-
0
tion in enteric versus blad d er-d rained sim u ltaneou s p ancreas–kid ney
1993-1995 1996-1998 1999-2002 transp lant recipients. Transplantation 1998;66:1746–1750.
Transplant era 20. Trop pm ann C, Gru essner AC, Bened etti E, et al. Vascu lar graft throm -
bosis after p ancreatic transp lantation: u nivariate and m u ltivariate
FIGURE 49.16. Pancreas allograft 1-year rejection rates according to op erative and nonop erative risk factor analysis. J Am Coll Surg 1996;
transplant era. Outcomes based on data from the Organ Procurement and 182:285–316.
Transplant Network (OPTN) as of J anuary 2, 2004. Outcomes represent all US 21. Booster MH , Schoenm akers EA, Rijnd ers AJ, et al. Perfu sion im aging of
cases of simultaneous pancreas-kidney (SKP) transplant and pancreas-alone pancreas allografts u sing technetiu m -99 m hexam ethyl p rop ylene
transplants performed from J anuary 1993 to December 2002. am ine oxim e. Transplant Int 1992;5(Su p p l. 1):S265–S267.
22. Gilabert R, Fernand ez-Cru z L, Real MI, et al. Treatm ent and outcom e of 35. Marks WH , Borgstrom A, Sollinger H , et al. Seru m im m u noreactive
pancreatic venou s graft throm bosis after kid ney—p ancreas transp lan- anod al tryp sinogen and u rinary am ylase as biochem ical m arkers for
tation. Br J Surg 2002;89:355–360. rejection of clinical w hole-organ pancreas allografts having exocrine
23. Barone GW, Webb JW, H u d ec WA. The enteric d rained p ancreas trans- d rainage into the u rinary blad d er. Transplantation 1990;49:112–115.
plant: another p otential sou rce of gastrointestinal bleed ing. Am J Gas- 36. Perkal M, Marks C, Lorber MI, et al. A three-year exp erience w ith
troenterol 1998;93:1369–1371. serum anod al trypsinogen as a biochem ical m arker for rejection in pan-
24. Sollinger H W, Messing EM, Eckhoff DE, et al. Urologic com p lications creatic allografts. False p ositives, tissu e biop sy, com p arison w ith other
in 210 consecutive sim u ltaneou s p ancreas–kid ney transplants w ith m arkers, and d iagnostic strategies. Transplantation 1992;53:415–419.
blad d er d rainage. Ann Surg 1993;218:561–568. 37. Prieto M, Su therland DE, Fern and ez-Cru z L, et al. Exp erim en tal an d
25. West M, Gruessner AC, Metrakos P, et al. Conversion from blad d er to clin ical exp erien ce w ith u rin e am ylase m on itorin g for early d iagn o-
enteric d rainage after p ancreaticod u od enal transp lantations. Surgery sis of rejection in p ancreas transp lantation. Transplantation 1987;43:
1998;124:883–893. 73–79.
26. Bened etti E, Gru essner AC, Trop p m ann C, et al. Intra-abd om inal fu n- 38. Mu nn SR, Engen DE, Barr D, et al. Differential d iagnosis of hyp oam y-
gal infections after p ancreatic transp lantation: incid ence, treatm ent, lasu ria in p ancreas allograft recip ients w ith u rinary exocrine d rainage.
and ou tcom e. J Am Coll Surg 1996;183:307–316. Transplantation 1990;49:359–362.
27. Sibley RK. Pancreas transplantation. In: Sale GE, ed. The Pathology of organ 39. Gru essner RWG, Dunn DL, Tzard is PJ, et al. Sim u ltaneou s p ancreas
transplantation. Boston, MA: Butterworth–Heineman; 1990:179–215. and kid ney transp lants versu s single kid ney transplants and previou s
28. N akhleh RE, Gru essner RWG, Sw anson PE, et al. Pancreas transp lant kid ney transp lants in u rem ic p atients and single p ancreas transp lants
pathology: a m orp hologic im m u nohistochem ical, and electron m icro- in nonu rem ic d iabetic p atients: com p arison of rejection, m orbid ity and
scopic com p arison of allogeneic grafts w ith rejection, syngeneic grafts, long-term ou tcom e. Transplant Proc 1990;22:622–623.
and chronic p ancreatitis. Am J Surg Pathol 1991;15:246–256. 40. Gru essner AC, Sutherland DE. Pancreas transp lant ou tcom es for
29. N akhleh RE, Sutherland DER. Pancreas rejection: significance of United States (US) and N on-US cases as reported to the United N et-
histopathologic find ings w ith im plication of classification for rejection. w ork for Organ Sharing (UN OS) and the International Pancreas Trans-
Am J Surg Pathol 1992;16:1098–1107. p lant Registry (IPTR) as of October, 2002. In: Cecka JM, Terasaki PI, ed s.
30. H u m ar A, Khw aja K, Ram charan T, et al. Chronic rejection: the next Clinical Transplants 2002. Los Angeles, CA: UCLA Tissu e Typ ing Labo-
m ajor challenge for pancreas transplant recipients. Transplantation 2003; ratory, 2002:41–77.
76:918–923. 41. Kaufm an DB. Ind uction therap y. In: Gru essner RWG, Su therland DE,
31. Pap ad im itriou JC, Drachenberg CB, Klassen DK, et al. H istological ed s. Transplantation of the pancreas. N ew York: Sp ringer; 2004:267–300.
grad ing of chronic p ancreas allograft rejection/ graft sclerosis. Am J 42. Gru essner AC, Su therland DE. Analysis of United States (US) and N on-
Transplant 2003;3:599–605. US pancreas transp lants reported to the United N etw ork for Organ
32. Dragsted t LR. Som e p hysiologic p roblem s in su rgery of the p ancreas. Sharing (UN OS) and the International Pancreas Transplant Registry
Ann Surg 1943;118:576–593. (IPTR) as of October, 2001. In: Cecka JM, Terasaki PI, ed s. Clinical trans-
33. Tyden G, Gunnarsson R, Ostman J, et al. Laboratory findings during rejec- plants 2001. Los Angeles, CA: UCLA Tissu e Typ ing Laboratory, 2001:
tion of segmental pancreatic allografts. Transplant Proc 1984;16:715–717. 41–72.
34. Cheng SS, Mu nn SR. Posttransp lant hyp eram ylasem ia is associated 43. Kaufm an DB, Leventhal JR, Gallon LG, et al. Technical and im m u no-
w ith d ecreased patient and graft su rvival in pancreas allograft recipi- logical p rogress in sim u ltaneou s p ancreas–kid ney transp lantation.
ents. Transplant Proc 1994;26:428–429. Surgery 2002;132:545–555.
CHAPTER
50
Complications of
Pulmonary Transplantation
Sara A. Hennessy, Bryan F. Meyers, and Christine L. Lau
Over the past three decades lung transplantation has become lungs w ill occasionally arrive at the recipient op erating
an accepted treatment option for a variety of end-stage pul- room w ith insu fficient atrial cu ff or inju ries to the p u l-
monary diseases. Improvements in organ preservation, surgi- monary vein orifices. When inju ries d o occu r, they m ost
cal techniques, infection prophylaxis, and immunosuppression frequ ently involve the right inferior p u lm onary vein. Such
medications have resulted in durable and steady improve- injuries usually occur as a resu lt of poor visibility or u nd u e
ments in lung transplant outcomes and have allowed for haste d u ring the d ivision of the left atrial cu ff (2). When a
expanded uses of lung transplantation. As a result of these p u lm onary vein orifice has been lacerated , rep air begins by
evolutionary changes, recipients are surviving longer after d ivid ing the p ericard iu m overlying the vein, exp osing the
transplant and some late complications arising from the pro- vessel u ntil it d isap p ears into the lu ng p arenchym a. Sm all
cedure and years of immunosuppression are becoming branches of the vein m ay have been d ivid ed if the vein ori-
increasingly evident. It is thus important to have a working fice has been entered . These are id entified and oversew n to
knowledge of the common complications, when these com- p revent trou blesom e bleed ing after rep erfu sion.
plications are most likely to occur, and how best to treat them. Casu la et al. (3) have d escribed a techniqu e of augm ent-
ing the p ulm onary veins u sing d onor p ericard iu m w hen
■ TECHNICAL COMPLICATIONS the left atriu m cu ff is inad equ ate. This m ethod can be u sed
to create a cu ff even w hen the su p erior and inferior p u l-
It is important to identify and correct technical complications monary veins have been com p letely sep arated . A ru nning
that arise during the lung transplant operation. Transplant 5–0 p olyp rop ylene su tu re is u sed arou nd each vein orifice,
operations of all types are unique in that they have two com- tacking the intim a to the p ericard iu m and creating a “neoa-
ponents: the retrieval of the organ from the donor and the trial cu ff.” Scissors are then u sed to trim the new ly created
implantation of the organ into the recipient. Technical compli- p ericard ial cu ff and sep arate it from the other hilar struc-
cations can occur during either phase of the operation, but the tu res. This p ericard ial cu ff su bstitu tes for d onor atriu m in
main burden of either type of complication will fall upon the the atrial anastom osis. Alternatively, d onor su p erior vena
recipient. A unique exception to that statement occurs in the cava or red u nd ant d onor pu lm onary artery can be used for
instance of living-related lobar transplantation, a phenome- the reconstru ction if there is inad equ ate tissu e.
non in which two living donors each donate a lower lobe of
one lung to allow the recipient to receive bilateral lobes as
lung replacements. In this extraordinary situation, three per- Pulmonary Artery Injuries
sons are susceptible to perioperative complications. This The bifurcation of the pu lm onary artery should alw ays be
chapter will focus on complications borne by the recipients, left attached to the lu ng graft at the tim e of p rocu rem ent.
but interested readers can learn about potential pitfalls for Even w hen a heart transp lant is p lanned from the sam e
lobar donors by reviewing the report by Battafarano et al. (1). d onor, d ivision of the p u lm onary artery at the d istal extent
of the m ain tru nk, p roxim al to the bifu rcation, leaves su ffi-
■ Suboptimal donor procurements cient length of artery for the safe im p lantation of the heart.
Com m on locations for pulm onary artery injuries d ur-
Atrial Cuff and Pulmonary Vein Injuries ing the d onor p rocu rem ent inclu d e the right p u lm onary
Despite the best efforts of both the heart and lu ng procu re- artery as it travels behind the aorta or, even m ore p roblem -
m ent team s to equ itably share the left atrial cuff, the d onor atic, p osterior to the su p erior vena cava. Since the right pu l-
m onary artery is su bstantially longer than the left, inju ry to
Sara A. Hennessy: University of Verginia. Charlottesville, this vessel behind the aorta rarely requires rep air and the
Virginia artery can be sim p ly trim m ed d istal to the laceration. More
Bryan F. Meyers: Washington University School of m ed i- serious injuries to the right pulm onary artery can occur
cine, St. Lou is, MO 63110 d eep to the su p erior vena cava. At this location, the first
Christine L. Lau: University of Michigan, Ann Arbor, MI branch of the right p u lm onary artery can be lacerated , and
48109 rep air, rather than trim m ing, is requ ired . The laceration can
656
Chapter 50 • Complications of Pulmonary Transplantation 657
sim p ly be rep aired in m ost cases, bu t if a m ore com p lex tissu e. The u se of electrocau tery to d issect m ed iastinal
reconstru ction of the tru ncu s anterior is requ ired , a p atch ad hesions w ill greatly increase the risk of p hrenic nerve
or com p lete reim p lantation m ay be u sed to p revent loss of injury.
d iam eter in the repaired vessel. The repair can be p er- If a p hrenic nerve is inju red , little can be d one to rem ed y
form ed w ith a segm ent of d onor vena cava, azygou s vein, the situ ation acu tely. It can be associated w ith increased
or red u nd ant d onor p u lm onary artery. m orbid ity, p rolonged intensive care u nit stay, prolonged
ventilation, and greater need for tracheostom y (7). In the
Bronchial and Parenchymal Injuries setting of bilateral transp lant, the fact that both lu ngs are
It is u nu su al for any significant inju ry to occu r to the lu ng being rep laced w ill m itigate the im p act of a unilateral
parenchym a or m ain bronchi d uring procu rem ent. Most p hrenic inju ry. In these circu mstances, the overall ou tcom e
parenchym al inju ries w ou ld sim ply result in a p rolonged w ill be satisfactory and there is a risk for u nd errep orting of
air leak after im p lantation. Special care should be taken to com p lications. If a p hrenic nerve inju ry occu rs d u ring a
avoid inju ry to the lu ng parenchyma w hen the im p lanta- u nilateral transp lant, the transp lant’s benefit to the patient
tion is to be p erform ed w ith card iopulm onary byp ass, as w ill be greatly d im inished . It has been exceed ingly rare in
even sm all parenchym al injuries m ay lead to end o- ou r exp erience or in the rep orted literatu re for a p atient to
bronchial bleed ing u nd er circum stances of profou nd anti- requ ire d iap hragm atic p lication after lu ng transp lantation.
coagulation for bypass.
Parenchym al injury in a d ifferent sense can occu r in an Hemorrhage
atrau m atic m anner d ue to technical problem s w ith d eliv- H em orrhage w as once a frequ ent com p lication after lu ng
ery of the flush solu tion u sed to cool and preserve the lungs transp lantation. Ind eed , in the early exp erience of som e
d u ring the p eriod of extracorporeal ischem ia. Inad equ ate p rogram s u nd ertaking heart–lu ng and en bloc d ouble-lung
flushing of the lu ngs m ay lead to profou nd ischem ia reper- transp lants, ap p roximately 25% of p atients requ ired reop-
fu sion inju ry and poor initial graft function. One extrem e eration for postoperative hemorrhage. H ow ever, w ith cur-
exam ple occu rred in a bilateral lu ng transplant perform ed rent su rgical techniqu es, such as posterolateral thoracotom y
by the au thors for cystic fibrosis. On the routine p ostop era- for single-lu ng transp lantation and th e “clam shell” or
tive p erfu sion scan, no flow w as seen perfu sing the left “sternal-sparing clamshell” incisions for bilateral lung
lung. A p u lm onary arteriogram d em onstrated a p atent rep lacem ent, su rgical exp osu re is su p erb (8).
anastom osis w ithou t evid ence of technical flaw s to accou nt
for the absent blood flow in the lung. Re-exp loration Pulmonary Hypertension and Hypoxemia
revealed an ed em atou s ischem ic lu ng w ith severe rep erfu - Persistent p ulm onary hypertension and unexplained
sion inju ry, requ iring rem oval of the graft. The conclu sion hyp oxem ia can occu r as a resu lt of stenosis at the p u l-
w as that the flu sh of the p reservative solu tion had som e- m onary artery anastom osis. A nu clear p erfu sion scan that
how been d irected d ow n the right pu lm onary artery pref- d em onstrates less than anticip ated flow to a single-lu ng
erentially and exclusively, thu s exposing the left lu ng to the graft or u nequ al d istribu tion of flow in a bilateral lu ng
“no-reflow p henom enon” d ue to severe ischem ic inju ry. recipient can suggest this problem. Occasionally, trans-
esophageal echocard iography can visualize a stenotic vascu-
■ Complications during recipient operation lar anastomosis. Contrast angiography should be performed
in any p atient for w hom there is su ch a concern. At the tim e
Phrenic Nerve Injuries of angiograp hy, th e p ressu re grad ien t across the p u l-
The incid ence of phrenic nerve injury varies from 7% to m on ary artery anastom osis shou ld be d eterm ined . A gra-
30% (4,5). Dense ad hesions p resent at the tim e of exp lanta- d ient of 15 to 20 m m H g is com m only encou ntered ,
tion can increase the risk of bleed ing, phrenic nerve, and esp ecially in single-lu n g recip ien ts in w h om m ost card iac
left recu rrent nerve injuries. These ad hesions are m ost ou tp u t m ay be d irected to the transp lanted lu n g or in
likely to be present in patients w ith septic lu ng d iseases bilateral recip ients w ith a h igh card iac ou tp u t. Th e clin i-
(cystic fibrosis and bronchiectasis) and in p atients w ho cal situ ation d ictates the need for an astom otic revision.
have had p reviou s thoracic su rgery. Particularly, d ense Dram atic red u ction in flow shou ld not be accep ted , as the
ad hesions have been seen in em p hysem a patients w ho d onor bronchu s is totally d ep end ent on p u lm onary arte-
have und ergone previous lu ng volum e red uction su rgery. rial collateral flow.
In a m u lticenter experience of 35 lu ng transplant p atients Com prom ised flow across the atrial anastom osis can
w ho had p reviou sly u nd ergone lu ng volu m e red u ction also occu r as a resu lt of u nsatisfactory anastom otic tech-
surgery, p hrenic nerve inju ry w as record ed in tw o p atients niqu e. Im p aired venou s ou tflow resu lts in elevated venou s
(5.7%) (6). Frequ ently, the phrenic nerve is ad herent to the p ressu re and ip silateral p u lm onary ed em a. Pu lm onary
lung volu m e red uction staple line and m akes its d issection artery p ressu res rem ain u nexp ected ly high in this situa-
ted iou s and d angerou s. To avoid injury to the p hrenic tion, and flow throu gh the graft is less than expected .
nerve, w e have opted to leave the staple line and a sm all Transesophageal echocard iography is often u sefu l in visu-
am ou nt of resid u al lung tissue attached to the p hrenic alizing the p atency and flow throu gh the atrial anasto-
nerve u sing a lung stapler to d ivid e the d ensely attached m oses. Contrast stu d ies m ay be help fu l in d em onstrating a
red u ced level of flow throu gh the anastom osis. Op en and forced exp iratory volu m e in 1 second after lu ng trans-
exploration is occasionally necessary to confirm the d iag- p lantation (12). These com p lications can be associated w ith
nosis and cond uct ap propriate repair. p rolonged need for ventilatory su p p ort, m ed iastinitis,
osteom yelitis, and even d eath (18). Many grou ps have
Sternal Complications d evelop ed m ethod s to im p rove fixation in the transsternal
Historically, bilateral lung transplantation has been done bilateral thoracotom y incision from single (11) and d ouble
through a median sternotomy and more recently through the p lating (15) to d ifferent w iring techniqu es (12,13); how ever,
so-called “clam-shell” incision or bilateral transsternal thora- com p lications continu e to p ose a challenge. Meyers et al.
cotomy (transverse thoracosternotomy) (9,10). This tech- and other grou p s ad vocate avoid ing sternal d ivision alto-
nique provid es extensive exposure to the hila and bilateral gether w ith bilateral anteriolateral thoracotom ies, w hich
p leu ral sp aces an d access to th e great vessels (11–14). have been demonstrated to provide adequate exposure in
However, this technique has some draw backs and is associ- most circumstances (2,12,14,19). Additionally, in rare selected
ated w ith a series of complications. cases, the use of modified approaches, such as a combined
The incid ence of sternal com p lications after lu ng trans- left posterolateral and right anterior thoracotomy, is advo-
plantation can range from 32% to 46% and in som e lu ng cated to optimize the left hilar exposure without the need for
transp lant recip ients lead s to significant m orbid ity and either sternal division or for a separate positioning, prepar-
even m ortality. Sternal com plications after lu ng transp lan- ing, and draping.
tation can inclu d e sternal overrid e, d ehiscence or d isru p - A d eep sternal w ou nd infection is a notoriou s com p lica-
tion, infection, and pseu d oartrosis. Lung transp lant tion after op en-heart su rgery, and p atients u nd ergoing
recip ients m ay be p articu larly p rone to p oor sternal healing lu ng transp lantation are not an exem p tion. Bacterial infec-
becau se of their d ebilitated state (osteoporosis, p oor nu tri- tions accou nt for the m ajority of sternal w ou nd infections,
tional statu s, d iabetes m ellitus, obesity, and heavy sm ok- Staphylococcus being the m ost com m on p athogen (20); how -
ing) and the routine use of perioperative corticosteroid s ever, fu ngal infections have been rep orted (21). The inci-
and postop erative im m u nosu ppression (12,13). d ence of sternal w ou nd infections can vary, bu t typically
Sternal d isru p tion, com m only called “sternal overrid - range from 0.4% to 8.8% (22–24). They classically occu r
ing,” is a com m on com plication in sternal healing. Brow n w ithin the first 30 d ays after transp lantation. The p resenta-
et al. (15) rep ort a p revalence of 36% for sternal d isru p tion tion of sternal w ou nd infections can occu r along a sp ec-
in transverse bilateral thoracosternotom y for lu ng trans- tru m from sterile w ou nd d ehiscence to m ed iastinitis and
plantation at their institu tion, and they cite d isru ption rates sternal osteom yelitis. Patients u su ally p resent w ith fever,
of 20% to 60% at institu tions w orld w id e. Sternal overrid ing elevated w hite blood cell cou nts, tachycard ia, and an ery-
occu rs becau se of the tend ency tow ard angu lation and them atou s, ed em atou s, tend er w ou nd site w ith or w ithout
anterior d isp lacem ent of the d istal sternum , and it ap p ears d rainage. The d iagnosis is fu rther confirmed w ith chest
to be u niqu e to the bilateral transsternal thoracotom y (16). rad iograp hs, cu ltu res, and com p u ted tom ograp hic scans.
There is a translational m ovem ent that is not p revented by Treatm ent requ ires op erative and bed sid e w ou nd d ebrid e-
sternal w ires. The solu tion to sternal overrid e has been the m ent w ith antibiotics and p ossible reconstru ction p roce-
ad d ition of coaxial stabilization: either by long, thin d u res in the fu tu re. Sternal w ou nd infections are associated
Kirschner w ires or short, stout Steinm ann pins, p laced w ith p rolonged hosp ital cou rse, increased hosp ital costs,
w ithin the cancellou s bone of the sternu m to help p revent and significant m orbid ity and m ortality for the patient.
sternal overrid e and translational m ovem ent at the bony Long-term effects inclu d e chronic p ain, sternal instability,
closu res. H ow ever, these w ires have a tend ency to m igrate and cosm etic d efects (20).
and have been rem oved in patients after m igration from
the sternu m to variou s locations in the bod y. Su ch
retrievals have requ ired interventions ranging from local
anesthetic to liberate a w ire erod ing through the anterior The num erous com plications that can occur after trans-
chest w all to general anesthesia w ith laparoscopy to p lantation often occu r along a pred ictable tim e course.
rem ove a Kirschner w ire from the pouch of Dou glas. Ster- Detailed d iscussion of the m ost imp ortant com plications
nal d ehiscence is d efined as “the total d isru ption of surgical follow s.
sutu res w ith or w ithou t infection” (11), and it is associated
w ith significant m orbid ity (34%) and m ortality (26%)
(12,17). Sternal (d eform ed or angled healing), nonu nion
■ Ischemia–reperfusion injury
(p ersistent sternal fracture at least 3 m onths after su rgery Ischem ia–rep erfu sion inju ry is one of the most im portant
or 6 m onths after trau ma w ithout evid ence of infection or com p lications of lu ng transp lantation, affecting 10% to 25%
healing), w ou nd infection and / or broken fixation w ires of all lu ng transp lant recip ients (25–28). It rep resents the
can preced e sternal d ehiscence (11). m ost frequ ent cau se of early m ortality and p rolonged ICU
Sternal d isru p tion or overrid ing and sternal d ehiscence stay. Ischem ia–rep erfu sion inju ry encom p asses an array of
can lead to both restrictions in chest w all m ovem ent and d efinitions, inclu d ing p rim ary graft d ysfu nction, im planta-
com pliance (16), resulting in low er forced vital cap acity tion resp onse, acu te lu ng inju ry, and hyp eracu te rejection
(29). Mortality rates are significantly higher in recip ients Ischem ia–rep erfu sion inju ry is characterized by noncar-
w ith ischem ia–reperfusion inju ry, and those w ho d o su r- d iogenic p u lm onary ed em a and p rogressive lu ng inju ry
vive have significantly im paired physical fu nction (26) and over the first few hou rs follow ing im p lantation. In its m ost
an increased risk of chronic rejection or bronchiolitis oblit- severe form , ischem ia–rep erfu sion inju ry is d escribed as
erans synd rom e (BOS) (30). p rim ary graft failu re that p athologically ap p ears as d iffu se
A variety of d onor, recipient, and operative factors p lay alveolar d am age (Fig. 50.1). Irresp ective of the cause, it is
a role in the d evelopm ent of ischem ia–reperfu sion inju ry. im portant to establish a d iagnosis of early graft d ysfunc-
Som e inherent d onor risk factors inclu d e old er age, fem ale tion and ru le ou t other treatable cond itions. One m ay per-
sex, African-Am erican race, and history of sm oking. form op en lu ng biop sy at the tim e of im p lantation if graft
Acqu ired d onor risk factors inclu d e prolonged m echanical d ysfu nction is im m ed iately ap p arent in the op erating
ventilation, asp iration, traum a, and hem od ynam ic stability room . Ad d itionally, serological evalu ation for anti-H LA
(31). Whitson et al. (32) fou nd that increasing d onor age, antibod ies m ay reveal evid ence for hyp eracu te rejection in
d onor sm oking history, increasing preoperative p u lm onary som e of these p atients.
arterial p ressu re, and recipient d iagnosis w ere significant Fortu nately, severe rep erfu sion inju ry has not com -
risk factors for p rim ary graft d ysfu nction. Operative vari- m only been encou ntered in recent years. Su p erior strate-
ables associated w ith p rim ary graft d ysfu nction inclu d e gies of lu ng p reservation have evolved (33). It is clear
use of card iop u lm onary bypass and blood p rod u ction from exp erim en tal (34) an d clin ical w ork (35–38) that low
transfu sion (31). H yperacu te rejection is exceed ingly rare, p otassiu m d extran solu tion p rovid es su p erior p reserva-
bu t it m u st be a consid eration in cases of early severe lu ng tion relative to the high potassiu m preservation solu tions
d ysfunction. p reviou sly in u se. In ad d ition, exp erim ental w ork su ggests
A B
FIGURE 50.1. A: Chest radiograph showing severe right-sided ischemia–

reperfusion injury following bilateral lung transplantation. Right lung was
implanted first. B: Chest radiograph of the same patient after resolution of
C ischemia–reperfusion injury. C: Transbronchial biopsy showing diffuse alveo-
lar damage characteristic of ischemia–reperfusion injury.
that nitric oxid e ad d ed to the flu sh solu tion at the tim e of allograft d ysfu nction is rep orted by Eriksson and Steen
harvest p rovid es a preservation ad vantage (39). On the (54), w ho have su ccessfu lly u sed core cooling to red u ce
other hand , lu ng hyperinflation is an excellent m od el of oxygen requ irem ents and avoid ECMO w hile the lu ng
postrep erfu sion p u lm onary ed em a. One m u st therefore be inju ry heals.
particu larly carefu l to avoid lu ng hyperinflation d u ring
harvest and storage of the d onor lu ngs (40). Each of these
Airway complications
factors has contribu ted to a red uction in the frequ ency of
ischem ia–rep erfu sion inju ry. Airw ay com p lication s w ere form erly a m ajor cau se of
The notion of “controlled rep erfu sion” originally m orbid ity an d m ortality after p u lm on ary transp lanta-
d escribed efforts to red u ce card iac d ysfu nction after rep er- tion. Using stan d ard m eth od s of im p lantation, th e d on or
fu sion of acu tely ischem ic m yocard iu m at the tim e of coro- bron ch u s is ren d ered isch em ic, w ithou t reconstitu tion of
nary artery revascu larization. Recently, the u se of its system ic bronchial artery circu lation . The d on or
controlled rep erfu sion, in com bination w ith leu kocyte bron ch u s relies on collateral p u lm on ary artery blood
d ep letion (41–47), has show n p rom ise as a p reventive flow d u ring the first few d ays after transp lantation. It has
strategy for ischem ia–rep erfu sion inju ry. Lick et al. (48) been d em on strated th at p u lm onary collateral flow m akes
rep orted a sm all, nonrand om ized series in hu m ans u sing a su bstantial contribu tion to bronchial viability at the
this techniqu e and rep orted no rep erfu sion inju ry in the level of th e d istal bronchu s an d lobar origin . A shortened
treated cohort of p atients. At the tim e of rep erfu sion, d onor bronchial length (tw o rings p roxim al to the u p p er
leu kocyte-filtered , p harm acologically m od ified p erfu sate lobe takeoff) red u ces the length of d on or bronchu s
is p u m p ed into the new ly im p lanted p u lm onary artery at d ep end ent on collateral flow. Su p erior p reservation,
a controlled rate (200 m L/ m inu te) and p ressu re (20 m m im p roved sep sis p rop hylaxis, and better im m u n osu p -
H g) for 10 m inu tes. The lu ng is ventilated w ith 50% p ression have red u ced the incid ence of airw ay com p lica-
insp ired oxygen concentration d u ring the p eriod to fu r- tion. Recen tly, one grou p rep orts th at in a m u ltivariate
ther red u ce the op p ortu nity for oxygen rad ical–m ed iated analysis, the risk factors for d evelop m ent of an airw ay
rep erfu sion inju ry. com p lication w ere d u ration of ventilation in th e d onor
In cases of established ischem ia–reperfu sion inju ry, and the telescop ing techniqu e for the anastom osis (55). In
proper treatm ent inclu d es d iu resis and inotropic su p p ort a review of one exp erience, Date et al. (49) rep orted a
and m axim al ventilatory sup port w ith sim ultaneou s red u ction of th e p revalence of anastom otic com p lications
avoid ance of ad d itional ventilator-ind u ced injury. In m ost from 14% to 4%.
cases, the rep erfu sion inju ry w ill resolve over 24 to 48 Airw ay com p lications are id entified in a num ber of
hours. Inhaled nitric oxid e is of benefit in severe rep erfu - w ays. Rou tine p ostop erative bronchoscop ic su rveillance
sion inju ry as it d ecreases p u lm onary artery p ressu re and generally p rovid es early evid ence that an anastom otic
im proves the PaO2/ FiO2 ratio (49). Recently, inhaled com p lication has occu rred . On occasion, com p u ted tom og-
prostacyclin has show n prom ise as an econom ical alterna- rap hy, p erform ed for som e other ind ication, d em onstrates
tive to nitric oxid e (50). an u nexp ected airw ay stenosis or d ehiscence. CT scanning
Althou gh stand ard intensive ventilatory and p harm a- is a u sefu l d iagnostic tool in the evalu ation of d ocu m ented
cologic intervention generally su ffice, severe graft d ys- or su sp ected d onor airw ay com p lications (Fig. 50.2). Late
fu nction or coexisting card iac failu re m ay requ ire airw ay stenoses generally m anifest w ith sym p tom s of d ys-
extracorp oreal m em brane oxygenation (ECMO) su p p ort. p nea, w heeze, or d ecreased FEV1. Bronchoscop ic assess-
Investigators have rep orted resu lts of the u se of ECMO m ent confirm s the d iagnosis.
after lu ng transp lantation (51) and have fou nd the tech-
niqu e to be satisfactory w hen the lu ng failu re occu rs
im m ed iately ( 24 hou rs p ost-transp lant). The etiology of
graft failu re in these cases w as rep erfu sion lu ng inju ry.
The frequ ency of rep erfu sion inju ry severe enou gh to
w arrant this therap y w as 3% of all transp lant op erations.
When d eterioration occu rs after 24 hou rs, it is often m u lti-
factorial and w ill be associated w ith lasting p athologic
changes in the p u lm onary p arenchym a that are less likely
solved by tem p orary ECMO su p p ort. Com m on com p lica-
tions associated w ith ECMO after lu ng transp lantation
inclu d e hem orrhage, hem od ialysis, neu rologic and car-
d iac com p lications, and sep sis (52). Ailaw ad i et al. (53)
recently rep orted a significant im p rovem ent in m ortality
rate (from 80% to 25%) in lu ng transp lant recip ients w ith
FIGURE 50.2. CT scan suggestive of right bronchial anastomotic dehis-
ischem ia–rep erfu sion inju ry after ECMO in the m ost cu r- cence with a small amount of mediastinal air tracking from the right bronchial
rent era. An alternative ap p roach to severe, reversible anastomosis and multiple loculated pneumothoraces.
■ Bronchial necrosis/dehiscence Airw ay stenosis can present a significant managem ent

p roblem . Several end oscop ic techniqu es are available for
Bronchial d ehiscence occurs in approxim ately 1% to 10% of treatm ent su ch as balloon bronchop lasty, cryotherapy, elec-
lung transp lant recip ients (56). Dehiscence can be d ivid ed trocau tery, laser, bou gie d ilatation, and stent p lacem ent. A
into p artial and com p lete categories. Fortu nately, the right m ain bronchial anastom otic strictu re is generally
occu rrence of com plete d ehiscence is low. The m orbid ity m anaged easily by rep eated d ilatation and u ltim ate p lace-
and m ortality associated w ith d ehiscence vary consid er- m ent of an end obronchial stent. There is u su ally su fficient
ably based on the severity and associated infections (57). length for placement of a right m ain bronchial orifice stent
A norm al bronchial anastom otic su tu re line w ill w ithou t im p ingem ent of the right u p p er lobe bronchus. On
d em onstrate a narrow rim of ep ithelial slough that ulti- the left sid e, how ever, strictu res can be som e w hat m ore
mately heals. Occasionally, one can observe patchy areas of d ifficu lt to m anage. Dilatation of the d istal left m ain
sup erficial necrosis of d onor bronchial epitheliu m . These bronchu s is technically m ore d ifficu lt becau se of the angu-
areas are also of no concern and u ltim ately heal w ithou t lation of that bronchu s. In ad d ition, the lobar bifu rcation
cau sing p roblem s. Minor d egrees of bronchial d ehiscence im m ed iately d istal to the u su al site of anastom osis d oes not
are also of little long-term consequ ence. Mem branou s w all p rovid e a su itable length of bronchu s d istal to the stricture
d efects generally heal w ithout any airw ay com prom ise, for p lacem ent of large-caliber d ilating bronchoscop es.
w hereas cartilaginou s d efects u su ally resu lt in som e d egree Finally, silastic stents p laced across a d istal left m ain
of late strictu re. bronchial anastom otic strictu re m ay occlu d e the u pper or
Significant d ehiscence (50% of the bronchial circu m fer- low er lobe orifice as they brid ge the strictu re. Silastic stents
ence) may resu lt in com prom ise of the airw ay. This p rob- are tolerated excep tionally w ell. Patients m ay, how ever,
lem should be m anaged expectantly by m echanical requ ire d aily inhalation of N-acetylcystine to keep the
d ebrid em ent of the area to m aintain satisfactory airw ay stents p atent. d e H oyos et al. (60) rep orted that the stents
patency. A stent can be p laced only if the d istal m ain airw ay have resulted in d ramatic improvement in pulmonary func-
rem ains intact. Occasionally, a significant d ehiscence tion. Fortunately, m ost of these stents have proven to be
resu lts in d irect com m u nication w ith the p leu ral sp ace, requ ired on ly tem p orarily. After several m on th s, m ost
resu lting in p neu m othorax and a significant air leak fol- stented anastom otic strictures m aintain satisfactory p atency
low ing chest tu be insertion. If the lung rem ains com p letely w ithou t the stent in place.
expand ed and the p leu ral sp ace is evacuated , the leak w ill Self-exp and ing m etal stents have benefited from
ultim ately seal and the airw ay m ay heal w ithout significant im p ressive technological im p rovem ent in recent years.
stenosis. Sim ilarly, a d ehiscence m ay com m unicate d irectly These stents m aintain airw ay p atency at 80% im m ed iately
w ith the m ed iastinu m , resulting in significant med iastinal after p lacem ent and 45% long term (61). These stents com e
em p hysem a. If the lung rem ains com pletely expand ed and in a w id e variety of lengths and d iam eters, and they have
the p leu ral sp ace is filled , ad equate d rainage of the m ed i- been excep tionally easy to insert. In rare situations in
astinu m can be achieved by p lacing a d rain in close p rox- w hich the airw ays d istal to an anastom otic stricture are too
im ity to the anastom otic line by w ay of m ed iastinoscopy. sm all to accept a silastic stent or w hen a silastic stent w ill
This step w ill also resu lt in satisfactory healing of the anas- obstru ct one bronchu s w hile stenting another, the u se of a
tom osis, often w ithou t strictu re. self-exp and ing m etal stent m ay su it the p u rpose. A 54%
A high incid ence of p ostop erative airw ay d ehiscence overall incid ence of comp lications is rep orted w ith self-
has been recently rep orted w ith the early u se of sirolim u s exp and ing m etal stents, inclu d ing infection, granu lation
in lu ng transp lant recip ients (58). In a series of 15 p atients tissu e form ation, and stent m igration (57). One caveat is
treated in the early p ostop erative p eriod w ith sirolim u s, that granulation tissue w ill rap id ly overgrow an u ncovered
four experienced anastom otic d ehiscences and three of m etal m esh stent, som etim es m aking it im possible to
these fou r d ied . The u se of sirolim u s in the early p ost- rem ove.
transp lant p eriod shou ld be d iscou raged . Finally, a new ad d ition is a self-exp and ing hybrid p las-
tic stent containing the best features of the silicone and
m etal stents w ithou t interstices that allow granu lation tis-
■ Anastomotic stenosis su e ingrow th. The stent allow s for p lacem ent w ith flexible
Chronic airw ay stenosis is the m ost com m on airw ay com - bronchoscopy u nd er conscious sed ation and allow s for
plication (59) and it is reported in 1.6% to 32% of recip ients easy rem oval.
(57). There are tw o patterns of bronchial stenosis, one at the
su rgical anastom osis and the second a d istal segm ental
narrow ing, referred to as segmental nonanastom otic
■ Anastomotic infections
bronchial stenosis. It is u su ally seen w ithin 2 to 9 m onths Anastomotic infections occur commonly and usually
after transp lantation. Bronchial stenosis m ay be asym p to- involve opportunistic infections. Because of the inherent
matic or it m ay p resent w ith sym ptom s of d yspnea, cou gh, ischemia occurring at the bronchial anastom osis after lung
recu rring p ostobstru ctive p neum onia, or w heezing. Flexi- transplantation, fungal infections may develop at this site.
ble bronchoscop y is the gold stand ard for d iagnosis (57). Aspergillus and Candida have been id entified as potential
pathogens that can cause life-threatening bronchial anasto-

motic infection (62). N unley et al. (63) id entified 15 (24.6%)
saprophytic fungal infections involving the bronchial anas-
tomoses in 61 recipients, w ith the majority of these infections
due to Aspergillus species. Stenotic airw ay complications
w ere more frequently seen in recipients w ith anastom otic
infections (46.7%) compared to those without fungal infec-
tions (8.7%). Specific complications from fungal infections
arising at the bronchial anastomoses included bronchial
stenosis, bronchomalacia, and fatal hemorrhage. A variety of
interventions, including bronchial stenting, balloon d ilata-
tion, electrocauterization, laser d ebrid ement, and rad iation
brachytherapy, have been used to treat these complications.
Additionally, in this series, three fatalities w ere associated
(4.9%) w ith saprophytic bronchial anastomotic infections.
Diagnosis of an infection m ay be a challenge in som e
recipients becau se of a lack of sym ptom s and fever (57). A
d istinction betw een colonization and infection shou ld be FIGURE 50.3. CT scan showing a lung abscess that was aspirated and found
mad e based on clinical sym ptom s and bronchoscopic to be Actinomyces. Patient initially presented with fevers and chills. The patient
signs. If bronchoscop ic inspection reveals extensive anasto- was subsequently treated with ampicillin with resolution of the abscess.
motic p seu d om em branes, a biop sy of the site shou ld be
perform ed to ru le out an invasive fu ngal infection. The
op tim al treatm ent of bronchial anastom otic fu ngal infec- Mycobacterium tuberculosis, and atyp ical m ycobacteriu m
tion is u nknow n. Su ccess has been reported w ith a com bi- have been seen in lu ng transp lant recip ients (66,67). Analy-
nation of system ic and inhaled antifungal agents. The sis of trend s in ind ivid u al hosp ital bacterial su scep tibilities
ad d ition of the inhaled antifu ngal therapy seem s ap prop ri- shou ld gu id e selection of em p iric therap y w ith ad ju st-
ate becau se aerosolization allow s d irect d ru g d elivery to m ents as necessary w hen sensitivities are available. At one
the poorly vascu larized anastom osis. Debrid em ent of the institu tion, all lu ng transplant p atients receive a 7- to 10-d ay
site m ay also be necessary (64,65). course of postoperative broad -spectrum antimicrobial pro-
phylaxis (e.g., vancomycin and cefipime). This antibiotic
regim en is m od ified d epend ing on the resu lts of cu ltu res
■ Infections obtained from the d onor and recipient p rior to transplanta-
Lu ng transplant recip ients are at increased risk for a variety tion (especially in patients w ith cystic fibrosis w ho have
of infectiou s com p lications d u e to the chronic im m u nosu p - p reop erative p athogens w ith know n sensitivities). Antibi-
pression and abnorm al physiology of the p ost-transp lant otics m ay be con tin u ed d ep end ing on th e recip ien t’s
lung. Infections w ith typical bacterial pathogens and bronchial cu ltu res after transplantation.
opportu nistic infections are both com m on. Collectively, Blood stream infections have been id entified as an impor-
infections represent the lead ing cause of d eath in the early tant cause of early postoperative morbid ity and mortality. In
postoperative interval and rem ain an im portant cau se of one report, blood stream infection w as d ocumented in 25%
morbid ity and m ortality throu ghou t the post-transplant of lung transplant recipients, w ith S. aureus and Pseudomonas
period . Evid ence su ggests that m any early infections m ay aeruginosa singled out as the most common pathogens.
ind uce im m une and nonim m u ne inflam m atory responses Another series of lung transplant recipients also reported a
that p red isp ose the recip ient to acu te or chronic allograft mortality rate of 25% w ith bacterem ia in the im m ed iate
rejection, or both. p ostop erative p eriod (68). Pneu m onia and catheter-related
infection represented the most common etiologies for post-
transplant blood stream infection, and infection w as associ-
■ Bacterial infections ated w ith a significantly increased risk for postoperative
Bacterial infections are m ost com m on in the early post- d eath. These results highlight the importance of appropriate
transp lant p eriod and remain the prim ary cau se of m ortal- antibiotic selection and the need to minimize the d uration of
ity d u ring this tim e (66). The most com mon organism s central lines (69).
involved are those colonizing the d onor or the recip ient or
iatrogenic bacteria that populate ind ivid ual institutional ■ Viral infections
ICUs. Gram -negative pathogens such as Pseudomonas ssp .,
Klebsiella, and Haemophilus influenzae are resp onsible for Cytomegalovirus
most early p ost-transplant bacterial pneum onias, bu t Cytomegalovirus (CMV) d isease is the most common infec-
Gram -p ositive organism s su ch as Staphylococcus aureus are tiou s postoperative com plication after lu ng transp lantation.
also im p ortant. Less com m only Actinomyces (Fig. 50.3), This viru s cau ses infection in 13% to 75% of transplant
A B
FIGURE 50.4. A: Transbronchial lung biopsy showing Cytomegalovirus (CMV) pneumonitis with demonstration of CMV inclusion
bodies (hematoxylin and eosin). B: Demonstration of CMV inclusion bodies by immunoperoxidase staining.
patients d ep end ing on the specific d efinitions of infection p ositive on im m u nop eroxid ase stain) on tissu e biop sies
and on the typ e and d u ration of pharm acologic CMV p ro- (Fig. 50.4) or the isolation of CMV from a tissu e specim en in
phylaxis (27,70). Lung transplant recipients w ho are sero- the p resence of clinical find ings consistent w ith CMV infec-
logically CMV negative p reoperatively and w ho receive tion. Most CMV infections resp ond to 14 to 21 d ays of IV
serologically CMV-p ositive d onor lu ngs are at the highest ganciclovir (5 m g/ kg b.i.d .). The d ose shou ld be ad ju sted
risk of d evelop ing severe, life-threatening d isease from for leu kop enia and renal d ysfu nction. When p atients fail to
p rim ary infection. On the other hand , su ch infection is not resp ond to IV ganciclovir therap y, d ru g resistance shou ld
u su ally seen in d onor-negative/ recip ient-negative trans- be consid ered and Foscarnet or Cid ofovir therapy m ay be
p lants (70). The op tim al ap p roach to the p revention of institu ted (73). H ow ever, becau se of the significant nephro-
p ost-transp lant CMV infection rem ains controversial. toxicity of these second -line agents, form al testing for gan-
Most centers em p loy a regim en of 12 w eeks of IV ganci- ciclovir resistance should be perform ed w hen su spected .
clovir (5 m g/ kg/ d ay) post-transp lantation in the high-risk Acute renal failure has been reported in a lung transp lant
(d onor positive/ recipient negative) m ismatch patients. recip ient treated w ith Cid ofovir (74). Valganciclovir, an
Som e centers em p loy a shorter cou rse of IV ganciclovir oral ganciclovir d erivative w ith bioavailability com p arable
(e.g., 4 w eeks) in all “at-risk” lung recipients. In a rand om - to intravenou s form u lations of ganciclovir, has recently
ized p rosp ective trial, Kru ger et al. (71) have d em onstrated been introd u ced for u se in transp lantation. Currently
that hyp erim m u ne globu lin against CMV alone is ineffec- ongoing p rosp ective stu d ies w ill d efine the ind ications,
tive in the p revention of CMV virem ia or p neu m onitis after efficacy, and cost effectiveness of oral valganciclovir in the
lung transp lant (71). As an ad d itional preventive m easu re, lung transplant popu lation.
one m ay u se CMV-negative or leu kocyte-red u ced blood
prod u cts in all instances, except m ajor bleed ing requ iring Community-Acquired Respiratory Viral Infections
large volu m e rap id transfusion (70). Com m u nity-acqu ired resp iratory viral infections, includ -
With the ad d ition of these preventative strategies, the ing resp iratory syncytial viru s (RSV) ad enoviru s, parain-
tim ing and incid ence of CMV infection and CMV d isease flu enza, and influ enza, cau se significant m orbid ity and
in lu ng transp lant recipients has changed . Currently, CMV mortality in lu ng transp lant recip ients (75–80). These viral
infection and d isease tend s to occur later after transp lanta- resp iratory infections occu r over a broad tim e range after
tion. Rou tine CMV prophylaxis has led to the em ergence of transp lantation, and d ifferent m echanism s m ay accou nt for
antiviral d ru g-resistant strains of CMV. Risk factors for early and late p ost-transp lant infection. Early viral infec-
d eveloping a CMV d rug-resistant strain includ e CMV m is- tion m ay resu lt from nosocom ial transm ission or reactiva-
match betw een a seronegative recipient and seropositive tion of latent viru s. In contrast, late p ost-transplant
d onor, p rolonged prophylaxis w ith oral ganciclovir, and resp iratory viral infection is m ore likely to be com m u nity
aggressive im m u nosuppression (72). acqu ired . A seasonal variation is seen w ith RSV (Janu ary to
“CMV infection” refers to d etection of the viru s in the Ap ril), w hile infections w ith ad enoviru s and p arainflu enza
seru m or bronchial alveolar lavage u sing conventional cu l- occu r throu ghou t the year.
tu re, shell vial assay, or qualitative seru m assay (e.g., p oly- The m ajority of viral infections p rod u ce acu te sym p -
merase chain reaction or CMV DN A by hybrid captu re). tom s, inclu d ing cou gh, w heeze, d ysp nea, and fever. Pre-
“CMV d isease,” on the other hand , is d efined by the p res- sentation of influ enza m ay be atyp ical w ith gastrointestinal
ence of “cytom egalic” cells (CMV inclu sion bod ies or cells (GI) sym p tom s p red om inating. N ew rad iograp hic find ings
in lung transplant recipients w ith viral respiratory infec- the influ enza vaccine w as significantly im p aired . Although
tions ind icate severe infection and are a m arker for p oor vaccination w as less effective com p ared to nonim m u no-
prognosis (77). Sym ptom atic ad enoviral infection, in p ar- su p p ressed ind ivid u als, 50% of p atients still reached pro-
ticu lar, is typ ically associated w ith new rad iologic abnor- tective seru m antibod y titers against tw o of three viru s
malities and is frequ ently fatal (77). strains (88). Therefore, rou tine influ enza im mu nization is
Treatment options for respiratory viral infections are lim- still recom m end ed , bu t serologic testing m ay be ind icated
ited . Aerosolized ribavirin has shown benefit in the treat- (75). Im p ortantly, all close contacts shou ld receive
ment of RSV and parainfluenza infection in child ren (81). influ enza vaccination w ith the intend ed goal of d ecreasing
Intravenous imm unoglobulin to RSV has been used in pre- the risk of infection to the transp lant p atient. Lu ng trans-
vention and treatment of RSV infections in infants (80). p lant recip ients shou ld avoid contact w ith fam ily and
Although the efficacy of these agents in lung transplant friend s w ith resp iratory sym p tom s, esp ecially child ren, to
recipients remains unclear, it has been recommended that all m inim ize risks of acqu iring com m u nity viral infection. Fre-
patients with severe symptomatic RSV or parainfluenza qu ent hand w ashing should be encou raged after contact
infection receive aerosolized ribavirin. Ribavirin is also rec- w ith infected p atients.
ommend ed in patients w ith rad iographic abnormalities in
the setting of RSV or parainfluenza infection given the Fungal Infections
increased potential to progress to respiratory failure. Care Fungal infections are a m ajor p roblem after lu ng transplan-
for ad enovirus is currently supportive as no d efinitive thera- tation and occu r early and late after transp lant. Aspergillus
pies are currently available. A trial of reduced immunosup- and Candida accou nt for 80% of these infections (89,90)
pression appears w orthw hile, although the risk for rejection (Fig. 50.5). Risk factors for fu ngal infections inclu d e com -
must be consid ered . Reports of the use of intravenous rib- p licated p ostop erative cou rse, early fu ngal colonization,
avirin or immunoglobulin have suggested potential value in frequ ent bacterial infections, CMV infection, chronic rejec-
adenoviral infections in ped iatric, bone marrow recipient, tion, renal failu re, and age of recip ient (91).
and AIDS patients (38,82–84). Intravenous ribavirin has also Candida accou nts for the m ajority of fu ngal infections
been used with some success in a pediatric patient w ith ade- d u ring the first m onth after transp lantation. Candida albi-
noviral infection after liver transplantation (85). Treatment cans is com m only isolated from bronchial w ashings after
for influenza in nonimmunocompromised patients includ es transp lant and its p resence u su ally rep resents colonization
several potential d rugs, includ ing amantad ine, rimantad ine, (66), bu t it m ay also be invasive (92). Althou gh C. albicans is
and the newer neuraminidase inhibitors such as zanamivir the m ost comm on, there has been a recent shift tow ard
and oseltamivir (86,87). The use of these agents in lung non-albicans species.
transplant recipients requires further stud y. Aspergillus infections are categorized into infections of
Becau se treatm ent op tions for com m u nity-acqu ired the bronchial anastomosis, tracheobronchial tree, pneumo-
viral infections in lu ng transplant recipients are lim ited , the nia, or d isseminated d isease (90,91). Aspergillus can also rep-
main goal in this p opu lation is prevention. It is routine for resent colonization, bu t becau se of the p otential for invasive
all lu ng transp lant recipients to receive yearly influ enza life-threatening infections, strong consid eration need s to be
vaccines. Unfortu nately, the response to influenza vaccine given for treatm ent. More than 50% of cases of Aspergillus
in solid -organ transplant recipients is im paired and revac- colonization and infection occu r w ithin 6 months after
cination d oes not seem to im p rove the vaccine resp onse transplantation. Mortality rates associated w ith invasive
(81). In a series of heart transplant patients, the efficacy of Aspergillus pneu monia approach 40% to 80% and 90% to
A B
FIGURE 50.5. A: Transbronchial lung biopsy showing Cytomegalovirus (CMV) pneumonitis with demonstration of CMV inclusion
bodies (hematoxylin and eosin). B: Demonstration of CMV inclusion bodies by immunoperoxidase staining.
100% w ith d issem inated infection in one series of lu ng and significant treatm ent-lim iting toxicities. Fu rtherm ore,
transplant recipients (90,93). Risk factors for post-transplant the u se of inhaled am p hotericin B has been associated w ith
fungal infection are w ell d efined ; single-lung transplant, significant su bjective intolerance lead ing to treatm ent d is-
CMV infection, renal failure, chronic rejection, and p re- continu ation in u p to 50% of p atients (101).
transplant colonization or prior treated infection may id en- One lu ng transp lant grou p has recently d em onstrated
tify patients at higher risk for post-transplant infection (90). the safety and tolerability of inhaled am p hotericin B lip id
In patients w ith a single-lung transplant, one obvious com plex (ABLC) in 50 lu ng transp lant recip ients. Becau se
potential reservoir of p ersistent Aspergillus is the native of the lip id p rop erties, it w as hyp othesized that ABLC
lu ng (66,94). Asp ergillom a lesions found in the recip ient- w ou ld be m ore effectively nebu lized w ith greater p u l-
explanted lungs have been associated w ith red u ced p ost- m onary d ep osition than conventional am p hotericin B.
transplant survival (95). Patients w ith cystic fibrosis and Consistent w ith this hyp othesis, very low rates of intoler-
positive p reop erative spu tum cu ltu res for Aspergillus are at ance and very low rates of fu ngal infection w ere seen in
higher risk for postoperative infections (96). p atients w ho received nebu lized ABLC (102). Although
Nocardia infections are increasingly recognized as com - fu rther stu d y is need ed , nebu lized ABLC seem s a p rom is-
plications of lu ng transplantation (97). Althou gh Nocardia ing ap proach to prevent fungal infections w ithout system ic
asteroides accou nts for the m ost transplant-related nocar- toxicities after lu ng transp lantation.
d iosis, a case of d issem inated infection w ith N. brasiliensis
(98) in a single-lu ng transplant recipient has been rep orted .
Although the m ortality is high for im m unocom p rom ised
■ PLEURAL SPACE COMPLICATIONS
patients w ith N. brasiliensis, prom pt d iagnosis and early ■ Hyperinflation
initiation of appropriate therapy m ay im prove ou tcom e.
Rep orts of other fungal infections su ch as H istop lasm a, Acute Native Lung Hyperinflation
Coccid iom ycosis, Mucorm ycosis, Zygom ycetes, and Cryp - Acu te native lu ng hyp erinflation is d efined as m ed iastinal
tococcu s are also d ocum ented (66). Scedosporium apiosper- shift tow ard the transplanted lung w ith flattening of the
mum is an u ncom m on cau se of d issem inated infection, and ip silateral d iap hragm cau sing graft com p ression. This is
im p ortantly, it is resistant to am photericin B (99). Pneumo- associated w ith resp iratory d ysfu nction, p ossible w eaning
cystis carinii, now classified as a fungu s, rem ains a rare d ifficu lties, or hem od ynamic instability (103). Acute native
cau se of infection becau se of the rou tine u se of effective lu ng hyp erinflation can occu r after single-lu ng transp lan-
prop hylaxis in all lung transplant recipients. Dem atiaceou s tation, esp ecially in p atients w ith chronic obstructive pu l-
fu ngi, su ch as Mu corm ycosis, are also infrequ ent cau ses of m onary d isease. The incid ence of acu te native lung
postop erative infection. hyp erinflation ranges from 26% to 64% (103–105), w ith an
Treatment for fungal infection is based on the specific associated m ortality rate of 42% (103). Patients w ith an
organism causing the infection; amphotericin B has been the obstru ctive com p onent, high m ean p u lm onary artery pres-
d rug of choice for Aspergillus and Fusarium. N ew er options su res, FEV1 15%, resid u al volu m e 200%, and a left lung
that may be as effective w ith less toxicity includ e liposomal transplant m ay have a greater tend ency tow ard acute
formulations of amphotericin, voriconazole, and caspofun- native lu ng hyp erinflation (103,104).
gin. Voriconazole must be used w ith caution in lung trans- Conservative treatm ent consists of su pportive therapy
plant recipients becau se of its extensive list of know n d ru g w ith vasop ressors, ventilatory strategies aim ed at prolong-
interactions. H igh-d ose azole therapy (itraconazole and ing exp iration, and early extu bation. Patients can be placed
voriconazole) may be used for Sced osporium. Nocardia in a lateral d ecu bitu s p osition, w ith the graft in a nond e-
infections are treated w ith trim ethoprim –su lfam ethoxazole. p end ent p osition, to red u ce hyp erinflation in the native
Most cand id al infections can be treated w ith fluconazole. lu ng. H ow ever, this is not effective as a long-term strategy
N on-albicans Candida species, how ever, are increasingly or in the w eaning p rocess. Differential ventilation allow s
resistant to Diflucan but can be effectively treated by new for a d ecrease in ventilation of the hyp erinflated lu ng; how -
d rugs such as voriconazole. Single-lung transplant should ever, the u se of a d ou ble-lu m en tu be and the need for d eep
probably not be performed in patients w ith mycetomas as sed ation also hind ers the w eaning p rocess. Surgical treat-
ad equ ate removal of fu ngal organisms cannot be achieved m ent cou ld inclu d e lu ng volu m e red u ction su rgery of the
and the new ly transp lanted lu ng w ill be at increased risk native lu ng or retransp lantation. Prevention strategies in
of colonization and infection (95). Prolonged therap y is p atients w ith em physem atou s lu ngs can inclu d e d ouble-
requ ired for all fu ngal infections. lu ng transp lant, single-lu ng transp lant w ith contralateral
Becau se of the p otential m orbid ity and m ortality associ- lu ng volu m e red u ction su rgery, or exclu sive right-sid ed
ated w ith fu ngal infections, several antifu ngal prop hylactic single-lu ng transp lants (104,105).
strategies have been u sed in lu ng transp lant recip ients,
often emp loying either system ic or inhaled antifu ngal Lung Hyperinflation in Undersized Grafts
agents, or both (100). H ow ever, enthusiasm for the u se of Rou tinely after lu ng transp lantation, p atients are tem -
system ic antifu ngal therap ies is lim ited by the lack of in p orarily maintained on positive p ressu re ventilation w ith
vitro activity against som e infections, d ru g interactions, thoracostom y tu bes in p lace. In lu ng transp lant recipients
w ith u nd ersized grafts, the negative pleural pressu re that

occu rs from thoracostom y tu bes on su ction can lead to
altered resp iratory m echanics. Presum ably, in the enlarged
pleu ral sp ace, the negative pleu ral p ressu re inhibits the
lung’s elastic recoil and lead s to d etrim ental hyperinfla-
tion. With the hyp erinflation, alveoli d o not com p letely
d ecom p ress d u ring exhalation, resulting in an increase in
fu nctional resid u al capacity. As more m echanical breaths
are d elivered , a stacking of the breaths occurs and the lu ngs
fu nction on a flatter portion of the volu m e–pressure cu rve.
This can m anifest as increased airw ay p ressu res w ith a
higher p otential for barotrau m a. In extrem e cases, this can
lead to d etrim ental alveolar hyperexpansion and hem od y-
nam ic instability. Aw areness of the potential for acu te
hyp erinflation can lead to preventive m easures su ch as
avoid ance of thoracostom y tu be su ction or by placing tho-
racostom y tu bes on w ater seal w hile the patient is on p osi-
tive pressu re ventilation (106).
FIGURE 50.6. Chest radiograph showing empyema of the native lung fol-
Pneumothorax lowing single-lung transplantation.
The m ost frequ ent p leu ral com p lication after lu ng trans-
plantation is p neu m othorax (107,108). Any new, persistent,
rep orted that early p ostop erative p leu ral effu sions are not
or enlarging p neu m othoraces shou ld be p rom p tly evalu -
concerning if the flu id ou tp u t is stead ily d ecreasing, and
ated to id entify the cau se of the air leak. Any significant
the rem aind er of the clinical cou rse is ap p rop riate.
pneum othoraces shou ld be initially treated w ith the inser-
tion of a thoracostom y tube until fu rther evaluation. In a
Empyema
retrosp ective review of their lu ng transp lant recip ients,
H errid ge et al. (108) found that the m ajority of pneum otho- Pleu ral em p yem a is an u ncom m on com p lication follow ing
races resolved sp ontaneou sly or w ith chest tu be thoracos- lu ng transp lantation, bu t its occu rrence is associated w ith a
tom y and there w as no associated increase in m ortality. significant m ortality (Fig. 50.6). Sp ontaneou s d evelopm ent
A pneum othorax is encountered prim arily in tw o cir- of an em p yem a is rare. More com m only, an em pyem a
cu m stances. The m ost com m on circum stance is the d evel- d evelop s after a p rolonged air leak or as a resu lt of op en
op m ent of insignificant p neu m othoraces in p atients w ith lu ng biop sy p erform ed on a p atient receiving high-d ose
obstru ctive lu ng d isease, either em physem a or cystic fibro- corticosteroid s. Persistent air leak and failu re to achieve re-
sis, w ho have u nd ergone bilateral replacem ent and have exp ansion of the lu ng and su bsequ ent p leu rod esis resu lt in
received lu ngs sm aller than the p leu ral sp ace into w hich a chronic p leu ral sp ace that eventu ally w ill becom e
they w ere im p lanted . Often a m inim al d egree of bilateral infected . N u nley et al. (112) p erform ed a retrosp ective
pneum othorax occu rs su bsequent to chest tube rem oval. In review of 392 transp lant recip ients and fou nd em pyema
general, these p neu m othoraces can be ignored and the d ocu m ented in 14 p atients (3.6%). In this series, em pyem as
pleu ral air w ill eventu ally reabsorb and any rem aining tend ed to occur early in the post-transp lant period and
space w ill fill w ith fluid . Pneu m othorax can occur infre- 28.6% (4 p atients) w ith em p yem as d ied second ary to
qu ently as a result of airw ay d ehiscence w ith com mu nica- related infectiou s com p lications. N o p red om inant organ-
tion into the p leu ral space. This is a rare occurrence and is ism w as isolated in em p yem ic flu id w ith Gram -p ositive,
usu ally read ily m anaged by intercostal tube d rainage w ith Gram -negative, and sap rop hytic organism s seen. There
app rop riate re-exp ansion of the und erlying lu ng. w as no relationship betw een the d evelopm ent of an
em p yem a and the typ e of transp lant p erform ed or w hether
Pleural Effusion the transplant w as d one for a septic or nonseptic lu ng d iag-
Pleural effu sions are com m on, w ith a reported incid ence of nosis. Su rgeons have treated a nu m ber of p atients w ho
25%, after lu ng transplantation (108,109). Effusions occu r d evelop ed em p yemas by op en d rainage by rib resection or
becau se of increased capillary p erm eability d u e to by creation of a Clagett w ind ow or Eloesser flap . Interest-
ischem ia–rep erfu sion injury of the allograft, d isrup tion of ingly, an em p yema rarely occu rs as a resu lt of bronchial
lym phatic flow, hem orrhage, and acute lung rejection or d ehiscence in com m u nication w ith the p leu ral sp ace.
infection. Early in the postoperative period , these effu sions
are u su ally exu d ative and blood y and com m only sm all to
mod erate in size. Most effu sions resolve w ithin 9 d ays in
■ REJ ECTION
single-lu ng transp lant recipients (110) and 14 d ays in bilat- Both acu te lu ng allograft rejection and chronic lu ng allo-
eral lu ng transp lant recipients (111). Most groups have graft rejection contribu te su bstantially to m orbid ity in lu ng
transp lant recip ients. Chronic lu ng rejection rem ains the has been show n to red u ce early rejection rates (132).
major lim itation to long-term success in lung transplanta- Becau se of ease of ad m inistration, a low rate of sid e effects,
tion tod ay. H yp eracute rejection has only anecd otally been sim ilar efficacy, and few er second ary infections, the IL-2R
rep orted in the literatu re (113–115). Saint Martin et al. (116) blockers are becom ing the ind u ction agents of choice for
perform ed im m u noflu orescence w ith C3, im m u noglobin centers ad hering to su ch a p rotocol.
M, and im m u noglobin G and fou nd no evid ence of Treatment of acute rejection has tw o goals: to treat the
hu m oral rejection in 106 biopsies. In this rep ort, only one acute p roblem and to red uce the likelihood of further acute
patient had a high reactivity p retransp lant panel of reactive rejection episod es. Conventional therapy has been intra-
antibod ies (PRA), su ggesting a low risk for hyp eracu te venous methylpred nisolone in a d ose of 10 to 15 mg/ kg for
rejection. Conversely, others have reported im m u nohisto- 3 to 5 d ays (133). Althou gh this strategy often accomplishes
chem ical find ings of hu m oral injury in som e recipients resolu tion of perivascular infiltrates, airw ay-centered
w ith high PRA (117). Interestingly, investigators have inflam m ation has been m ore refractory to therap y. Depend -
recently rep orted evid ence su ggesting that a frequ ently ing on the m aintenance steroid d ose, 2 to 3 w eeks of an oral
occu rring sep tal cap illary inju ry synd rom e m ay rep resent steroid taper is usually prescribed . As acute therapy is initi-
hu m oral inju ry in lu ng allografts (118). ated , the maintenance imm unosup pression regimen should
be scru tinized . A frequ ent first ad justment is a sw itch from
maintenance cyclosporine to tacrolimus in the event of
■ Acute rejection cyclosporine toxicity or acute rejection episod es d espite
Acu te allograft rejection is one of the m ost com m on com - ad equ ate cyclosporine d osage (134,135). The roles of new er
plications follow ing lu ng transp lantation. Most recip ients agents su ch as sirolimus or leflu nomid e, a pyrimid ine syn-
experience at least one episod e of acute rejection w ithin the thesis inhibitor, are evolving in lu ng transplantation based
first year follow ing transp lant (119,120). In 1990, the Lu ng on su ccess in other solid -organ transplants (136–139). Low
Rejection Stud y Grou p d eveloped a system to characterize calcineurin inhibitor d rug levels w arrant investigation,
lung allograft rejection based on histologic criteria d etected esp ecially for new m ed ications activating the cytochrom e
in lu ng biop sy specim ens, w ith em phasis on p erivascu lar P450 enzyme pathw ay and enhancing calcineurin inhibitor
and interstitial infiltration of m ononu clear cells. N ote is metabolism (e.g., d ilantin, rifamp in, and nafcillin) (140).
also m ad e of the coexistence of airw ay inflam mation (121).
Mod est revisions in this system w ere d escribed in 1995
(122). In recent years, airw ay-centered inflam m ation (lym -
■ Chronic Allograft Rejection/BOS
phocytic bronchitis/ bronchiolitis) has been associated w ith The d escrip tive term “bronchiolitis obliterans synd rom e”
su bsequ ent d evelop m ent of chronic lu ng allograft d ysfu nc- has been u sed to d escribe a late d ecline from a p ostop era-
tion characterized by the p athologic lesion of bronchiolitis tive baseline forced exp iratory volu m e in 1 second (FEV1)
obliterans (123). In ad d ition, it is clear that there is an asso- that is not attribu table to acu te rejection, infection, or
ciation betw een frequ ency and severity of acu te rejection m ech an ical obstru ction d u e to a bronchial anastom otic
episod es and the su bsequent d evelopm ent of bronchiolitis com p lication . Th e p ath ologic lesion associated w ith this
obliterans (123). Thu s, early d etection of acu te rejection and d ecline is bronchiolitis obliterans (Fig. 50.7). A w orking
alteration of im m u nosup pression to d eal w ith this p roblem form u lation w as created to characterize an d grad e BOS
may have a significant im pact in the su bsequ ent red uction (141) an d has been recen tly revised (142). BOS is a very
of chronic lu ng allograft d ysfu nction. com m on cond ition follow ing lu ng transp lantation (143).
In the early years of lu ng transplant experience, clinical
param eters w ere often used to establish a clinical d iagnosis
of acu te rejection. Unfortu nately, d yspnea, low -grad e fever,
perihilar infiltrates, leu kocytosis, hyp oxia, and the clinical
resp onse to intravenou s bolu s d oses of corticosteroid are
nonsp ecific find ings. Pathologic assessm ent of m u ltip le
transbronchial biop sy sp ecim ens has p roven to be the
“gold ” stand ard for the d iagnosis of acu te lu ng allograft
rejection (121,124,125). Ind eed , m any program s have
ad op ted a p rogram of prophylactic surveillance trans-
bronchial biop sy (119,125–129). H ow ever, this strategy is
controversial and a num ber of active lu ng transplant pro-
gram s have aband oned it (130,131).
Since acu te rejection is a pred ictor of BOS, ind u ction
and m aintenance im m unosu ppression regim ens, as w ell as
treatm ent strategies for d ocu m ented acute rejection, are
subjects of intense interest. Ind uction therapy w ith either a FIGURE 50.7. Transbronchial lung biopsy showing bronchiolitis obliterans
cytolytic agent or an interleu kin-2 recep tor (IL-2R) blocker with scarring and fibrosis of the small airways (hematoxylin and eosin).
Most observers believe that every recip ient w ill d evelop occu rrence, bow el p erforation, ap p end icitis, cholecystitis,
som e d egree of BOS w ith long-term follow -up . Actu arial colitis, and p neu m atosis intestinalis (151). Post-transplant
freed om from BOS at 1, 3, and 5 years p ost-transp lant is lym phoproliferative d isease (PTLD) m ay p resent as an
82%, 42%, and 25%, respectively (144). acu te abd om inal p rocess, second ary to intu ssu scep tion or
The specific causes of BOS are not clear. Evid ence sug- bow el p erforation. Recip ients w ith cystic fibrosis are at
gests that both alloimmune and nonalloimmune mecha- increased risk for ad d itional abd om inal com plications such
nisms are important (145). Recipients w ho have more as gastric bezoars and d istal intestinal obstru ction syn-
frequent and severe episod es of acute allograft rejection are d rom e (152). Su rgical GI com p lications can occur at any
more likely to d evelop subsequent BOS (123). N onimmune tim e after transp lantation, and imm u nosu p p ression m ay
mechanism s are also important. These includ e airw ay injury initially m ask their severity. When em ergent operative
from primary graft d ysfunction, allograft infections (CMV), exp loration is requ ired , su ch an intervention has significant
airway ischemia, single-lung transplantation, noncompli- associated [u 5]m orbid ity and m ortality. Elective abd om i-
ance w ith immunosuppression, and gastroesophageal reflux nal su rgical proced u res can be perform ed safely in this
disease (GERD). Lung transplant recipients appear to have a p op u lation w ith accep table m orbid ity (153).
high incidence of GERD. Patients w ithout GERD have a More recently, GERD has received significant attention
much low er incid ence of BOS than those w ith uncorrected because of its association with chronic lung rejection or bron-
GERD. Improvem ent of BOS has been noted in recipients chiolitis obliterans. Although prevalent in end -stage lung
w ith GERD w ho und erw ent corrective fund oplication (146). patients, its occurrence is very common after lung transplan-
In one series, the United N etw ork for Organ Sharing d ata- tation. Up to 75% of recipients have some d egree of reflux
base w as reviewed for donor factors associated with the based on pH studies (154). Factors causing post-transplant
development of BOS in lung transplant recipients. Female GERD includ e vagal d amage, impaired cough and airway
donors, d onors w ho w ere not current smokers, donors w ith- mucociliary clearance, an immunosuppression d rug effect
out a history of myocard ial infarction, and d onors w ith or the preexisting presence of GERD (146). Treatm ent w ith
immunologic similarity to their recipients had longer BOS- proton pump inhibitors has not shown to be promising in
free survival. Recipients w ho received lungs w ith higher the prevention of BOS w hen associated w ith GERD (154).
partial pressures of oxygen in arterial blood developed more Nissen fundoplication has successfully been used to treat
BOS (147). lung transplant patients with d ocumented GERD. Antire-
Currently, the link between acute cellular rejection and flux surgery in lung transplant recipients has show n a sur-
BOS has mad e augmentation or changing immunosuppres- vival benefit and a d elay in onset of BOS, particularly if
sive med ication the mainstay of therapy (148). Until w e have performed before the late stages of the BOS (146,155).
a better und erstanding of the molecular and cellular mecha-
nisms of BOS, w e are not likely to make much progress in its
treatment. This goal is hampered by the lack of a suitable
■ Post-transplant lymphoproliferative disease
experimental mod el of the bronchiolitis obliterans lesion. A PTLD is a w ell-recognized com p lication after solid -organ
definitive solution for chronic allograft rejection may come and bone m arrow transp lantation w ith an incid ence
through the d evelopment of strategies to promote immune betw een 4% and 10% after lu ng transp lantation (156–159).
tolerance or permanent acceptance of the graft by the recipi- Investigators have rep orted a 6.1% incid ence of PTLD
ent w ithout the need for immunosuppression. after lu ng transp lantation in the ad u lt p op u lation (159).
The incid ence of PTLD is rep orted to be tw o to six tim es
higher in lu ng transp lant recip ients than other solid organ
■ NONPULMONARY COMPLICATIONS transp lants (160,161). PTLD inclu d es a sp ectru m of d isease
entities ranging from atyp ical lym p hoid p roliferation to
■ GI complications m alignant non-H od gkin lym p hom a (162,163). Most com -
GI com p lications are frequ ent in lu ng transp lant recip ients, m only, the neop lastic cells are of B-cell origin and there are
occurring in as m any as 50% of patients in som e series often associations betw een PTLD and the p resence of
(149). Frequ ently reported nonsu rgical GI com plications Ep stein–Barr viru s (EBV) (164). Cytotoxic T cells are
includ e esop hagitis, pancreatitis, gastric atony, ad ynam ic involved in d estroying cells p resenting EBV in the context
colonic ileu s, gastroesophageal reflu x, p eptic ulcer d isease, of MH C I. It has been p rop osed that an im m u nocom pro-
gastritis, GI bleed ing, CMV hepatitis, CMV colitis, d ivertic- m ised recip ient exp eriencing a p rim ary EBV infection m ay
ulitis, cholecystitis, and Clostridium difficile colitis/ diarrhea. not be cap able of d estroying the viru s-infected B cells,
N au sea is the m ost com m on GI com pliant, w hich is likely resu lting in EBV-d riven B-cell p roliferation. In lu ng trans-
secon d ary to m ed ication sid e effects (150). The m ajority p lant recip ients, a strong correlation has been reported
of these nonsu rgical GI com p lications occu r in the first betw een negative EBV serology prior to transplantation
m on th p ostop eratively and m ost resp ond to conservative and the su bsequ ent d evelop m ent of PTLD. Stu d ies have
therap y (149). Acu te abd om inal p rocesses requ iring su r- rep orted a 6.8- to 20-fold increased risk of d evelop ment of
gical intervention have a rep orted incid ence of 4% to 17% PTLD in recipients w ho had EBV-negative pretransplanta-
in lu ng transp lant recip ients and inclu d e, in d ecreasing tion (156,165). Som e have p rop osed that EBV carried in the
d onor lu ng lym phocytes results in a p rim ary infection in 20% to 40% in m u ltip le series (173–175) w ith a p eak of
the recip ient. H ow ever, som e reports have show n the recip - onset at d ay 2 to 3 p ostop eratively w ith 70% occu rring by
ient to be the origin of the lym phocytes in PTLD (112,166). p ostop erative d ay 4 (176,177). Dysrhythm ias likely occu r
The u se of ind u ction therapy (167) and the presence of second ary to op erative trau m a and su rgical d issection of
CMV infection (168) have both been su ggested as con- the atriu m , local inflam m ation, and catecholam ine p ro-
tribu ting factors to the d evelop m ent of PTLD. d u ction (175).
PTLD often occu rs in the first year after transp lantation Mason et al. (175) rep orted that 68 of their 333 lung
and show s a p red ilection for the thorax, m ost com m only transp lant recip ients d evelop ed p ostop erative atrial fibril-
the lu ng allograft (156–159). Cases of PTLD that p resent lation. Risk factors for atrial fibrillation w ere old er age,
after the first year, in contrast, are usually extrathoracic, p rim ary p u lm onary hyp ertension, and extrem es of w eight.
com m only arising in the abd om en and pelvis (159). In one Rate-controlling d ru g agents w ere su ccessfu lly used in 27%
series, of the 16 reported cases of PTLD that occu rred after of recip ients, w hile 7.5% requ ired antiarrhythm ics and 66%
the first year, 14 of 16 (88%) w ere extrathoracic. Late cases requ ired both agents. Card ioversion w as requ ired in 36%
of PTLD in the abd om en and p elvis occu r at a m ed ian tim e of lu ng transp lant recip ients (175). Another series reported
of 5.8 years after transplantation (169). Interestingly, in all that p atients w ith atrial d ysrhythm ias had higher rates of
late cases occu rring in the abd om en and pelvis, the recip i- reintu bation, ad d itional op erative intervention, and longer
ents w ere EBV p ositive prior to transplant. Late-occu rring ICU and hosp ital stays. Use of card iop u lm onary bypass,
abd om inal and p elvic PTLD cases w ere m ost com m only age of recip ient, and tim e on the w aiting list w ere id entified
malignant non-H od gkin lym phom as, and d espite aggres- as significant risk factors for atrial d ysrhythm ias (178).
sive therap y the prognosis w as poor. In contrast, the
patients w ho p resented w ith early PTLD, u nless d issem i- Renal Failure
nated at d iagnosis, had a favorable prognosis and often Renal failu re is a com m on com p lication follow ing lu ng
resp ond ed to sim p ly d ecreasing the level of im m u nosu p - transplantation that carries a significant m orbid ity and
pression (169). m ortality. In ou r recent review of ou r 346 lu ng transplant
Treatment of PTLD is based on the stage and progression recip ients, 9.5% d evelop ed acu te p ostop erative renal fail-
of d isease. Initially, a trial of red uction of immunosuppres- u re w ith 4.6% of those requ iring d ialysis. N one of the
sion is attempted , particularly w ith d isease limited to the p atients w ho requ ired d ialysis had recovery of their renal
allograft. Many investigators have recommended the simul- fu nction, and of those requ iring d ialysis, 75% d ied d u ring
taneous use of antiviral therapy (165). Although chemother- initial hosp italization versu s only 5.8% of p atients w ho d id
apy has been used in patients w ith widespread disease or not p rogress to d ialysis. Ishani et al. (179) review ed the
w ho have progression of d isease, treatment-related m ortal- cou rse of 219 lu ng and heart–lu ng transp lant recipients
ity is considerable. In one reported study, 75% of PTLD su rviving at least 6 m onths p ost-transp lant and fou nd that
patients treated with chemotherapy died as a result of sepsis by 6 m onths 200 p atients (91.3%) had a d ecrease in renal
(165). Recently, rituximab, a humanized anti-CD20 mono- fu nction. Dou bling of creatinine from p retransp lant base-
clonal antibod y, has show n promise as a treatment option line occu rred in 34%, 43%, and 53% at 1, 2, and 5 years,
(170). Verschuuren et al. (170) reported complete remission resp ectively. End -stage renal d isease occu rred in 16 lu ng
in three lung transplant patients treated w ith rituximab. transplant recipients (7.3%) at a median duration of 28
Complications occurred in tw o, one relapsed w ith a partial months. The majority of recipients who developed ESRD
CD20-negative PTLD and the other d eveloped hypogamma- had received cyclosporine (13 of 16), compared to only three
globulinemia w ith subsequent sepsis and d eath. Another w ho had received tacrolimus. Of the patients who devel-
series used rituximab as first-line treatment in six lung trans- oped ESRD, 44% (33) received hemod ialysis alone and 56%
plant recipients w ith PTLD and demonstrated complete (35) received kid ney transp lants. Risk factors associated
remission in four patients (171). w ith tim e to d ou bling of creatinine by m u ltivariate analysis
Preventative strategies have been contemplated. In adult w ere seru m creatinine at 1-m onth p ost-transp lant and the
lung transplantation, it does not appear prudent to match nu m ber of cu m u lative follow -u p p eriod s w ith the d iastolic
recipient and donor EBV status because 90% of the popula- blood p ressu re 90 m m H g. Com p ared w ith cyclosporine,
tion is EBV positive by the time they are 35 years old. This the u se of tacrolim u s in the first 6 m onths follow ing trans-
strategy may have more value in children who have a higher p lantation w as associated w ith a d ecreased risk for d ou-
percentage of EBV-negative recipients. Malou f et al. (172) bling of seru m creatinine.
rep orted that p rop hylactic u se of antiviral therap y m ight Risk factors inclu d e p eriop erative hem od yn am ic
reduce the incidence of PTLD. instability, in fection s, u se of calcineu rin in hibitors, and
u se of nep hrotoxic antibiotics (180). It is ap p aren t that
p revention of su bsequ ent renal failu re in lu ng transp lant
■ Atrial dysrhythmias recip ients requ ires p reserving ren al fu nction early in the
Atrial d ysrhythm ias occu r frequ ently after lu ng trans- cou rse of transp lan tation . Early id en tification of h igh -
p lantation and have been show n to increase hosp ital stay risk recip ients for renal d ysfu nction sh ou ld p rom p t
and p eriop erative m ortality (173). Prevalence ranges from aggressive blood p ressu re control in these recip ients and
consid eration of change in immunosuppressive protocol ■ REFERENCES

(181). Other stud ies have found the und erlying pulmonary
d iagnosis to be a risk factor for the subsequent d evelopment 1. Battafarano RJ, And erson RC, Meyers BF, et al. Periop erative com p li-
cations after living d onor lobectom y. J Thorac Cardiovasc Surg 2000;
of renal insufficiency. Recipients w ith cystic fibrosis had the
120(5):909–915.
greatest impairment in renal function, and recipients w ith 2. Parekh K, Patterson GA. Technical consid erations in ad u lt lu ng trans-
pulmonary hyp ertension had the least impairment (182). p lantation. Semin Thorac Cardiovasc Surg 2004;16(4):322–332.
3. Casu la RP, et al. Pu lm onary vein au gm entation for single lu ng trans-
Hyperammonemia p lantation. Ann Thorac Surg 2001;71(4):1373–1374.
4. Dorffner R, Eibenberger K, You ssefzad eh S, et al. Diap hragm atic d ys-
Hyperammonemia follow ing lung transplantation has been fu nction after heart or lung transp lantation. J Heart Lung Transplant
1997;16(5):566–569.
reported as a potentially fatal complication (183–185). The
5. Sh erid an PH Jr, Cheriyan A, Dou d J, et al. In cid en ce of p h renic n eu -
development of hyperammonemia appears to occur early in rop athy after isolated lu ng transp lantation. The Loyola University
the post-transp lant p eriod . In one recent stud y, 6 (4.1%) of Lu ng Transp lant Grou p . J Heart Lung Transplant 1995;14(4):684–691.
6. Lau CL, Gu thrie TJ, Chap arro C, et al. Lu ng transp lantation in recip -
145 lu ng transp lant recipients d eveloped hyperam m one-
ients w ith p reviou s lu ng volu m e red u ction su rgery. J Heart Lung
mia, all w ithin the first 26 d ays after transplantation (184). Transplant 2003;22(1):S183.
A high m ortality rate w as seen in the population that 7. Ahya VN , Kaw ut SM. N oninfectiou s p u lm onary com p lications after
lu ng transp lantation. Clin Chest Med 2005;26(4):613–622, vi.
d evelop ed hyp eram m onem ia (67% vs. 17%). The m ajority
8. Pasqu e MK, Coop er JD, Kiaser LR, et al. Im p roved techniqu e for bilat-
of p atients w ith hyp eram m onem ia d evelop neu rologic eral lu ng transplantation: rationale and initial clinical exp erience. Ann
sym ptom s, inclu d ing encep halopathy, lethargy, agitation, Thorac Surg 1990;49(5):785–791.
9. Patterson GA, Coop er JD, Gold m an B, et al. Techniqu e of su ccessfu l
seizu re, trem ors, and com a. Risk factors for the d evelop -
clinical d ouble-lung transp lantation. Ann Thorac Surg 1988;45(6):
ment of hyperam m onemia includ e m ajor GI com plications, 626–633.
use of total p arenteral nu trition, and lung transplantation 10. Wright C. Transverse sternothoracotom y. Chest Surg Clin N Am 1996;
6(1):149–156.
for primary pulmonary hypertension. Treatment of hyper-
11. Karnak D, Shah SS, Rozas MS, et al. Rep air of sternal d ehiscence after
ammonemia includes: hemodialysis, the discontinuation of bilateral lu ng transp lantation. J Thorac Cardiovasc Surg 2006;132(2):
all exogenous nitrogen, the provision of high caloric intake 425–426.
12. Meyers BF, Su nd aresan RS, Gu thrie T, et al. Bilateral sequ ential lu ng
to depress catabolism, and the ad ministration of enteral lac-
transp lantation w ithou t sternal d ivision elim inates p osttransp lanta-
tulose, neomycin, and agents used to treat congenital urea tion sternal com p lications. J Thorac Cardiovasc Surg 1999;117(2):
cycle defects (sodium phenylacetate, sodium benzoate, and 358–364.
13. Oto T, Venkatachalam R, Morsi Y, et al. A reinforced sternal w iring
arginine hyd rochloride) (186).
techniqu e for transverse thoracosternotom y closu re in bilateral lu ng
transp lantation: from biom echanical test to clinical ap p lication. J Tho-
Thrombotic Thrombocytopenic Purpura–Hemolytic rac Cardiovasc Surg 2007;134(1):218–224.
Uremic Syndrome 14. Venu ta F, Rend ina EA, De Giacom o T, et al. Bilateral sequ ential lu ng
transp lantation w ithout sternal d ivision. Eur J Cardiothorac Surg 2003;
An infrequent but potentially serious com plication follow - 23(6):894–897.
ing lung transplantation is throm botic throm bocytopenic 15. Brow n RP, Esm ore DS, Law son C. Im p roved sternal fixation in the
purp u ra (TTP)–hem olytic u rem ic synd rom e (H US). More transsternal bilateral thoracotom y incision. J Thorac Cardiovasc Surg
1996;112(1):137–141.
com m on in other solid -organ transp lants, especially kid - 16. Macchiarini P, Lad u rie FL, Cerrina J, et al. Clam shell or sternotom y
ney transp lants, these synd rom es are characterized by for d ou ble lung or heart–lung transp lantation? Eur J Cardiothorac Surg
m icroangiop athic hem olysis, throm bocytop enia, and renal 1999;15(3):333–339.
17. Wu LC, Renu cci J, Song DH . Rigid -p late fixation for the treatm ent of
failu re (187). Disease is m ost com m on w ith in th e first sternal nonunion. J Thorac Cardiovasc Surg 2004;128(4):623–624.
3 m on th s p ost-tran sp lan tation , and 96% of cases occu r 18. Gold m an G, N estel R, Snir E, et al. Effective techniqu e of sternu m clo-
w ithin the first year. This complication is associated w ith su re in high-risk p atients. Arch Surg 1988;123(3):386–387.
19. Lau CL, Patterson GA. Technical consid erations in lu ng transp lanta-
the use of calcineurin inhibitor therapy. One single-center tion. Chest Surg Clin N Am 2003;13(3):463–483.
stud y reports eight cases of tacrolimus-attributed TTP in 20. H u ssey LC, Leeper B, H ynan LS. Develop m ent of the sternal w ou nd
257 lung transp lant recipients (188). The critical component infection p red iction scale. Heart Lung 1998;27(5):326–336.
21. Lee J, Yew WW, Chiu CS, et al. Delayed sternotom y w ou nd infection
of treatment is prompt initiation of plasma exchange. In d u e to Paecilomyces variotii in a lu ng transp lant recip ient. J Heart Lung
ad d ition to plasma exchange, aspirin, d ipyrid amole, or glu - Transplant 2002;21(10):1131–1134.
cocorticoid s can be u sed (189). H emod ialysis or renal trans- 22. Abid Q, Nkere UU, Hasan A, et al. Mediastinitis in heart and lung trans-
plantation: 15 years experience. Ann Thorac Surg 2003;75(5):1565–1571.
plantation is requ ired in lu ng transp lant recip ients w ho 23. Losanoff JE, Richm an BW, Jones JW. Disru p tion and infection of
d evelop renal failure from this synd rome. Mortality is in the m ed ian sternotom y: a com p rehensive review. Eur J Cardiothorac Surg
range of 13% (187). 2002;21(5):831–839.
24. Rid d erstolpe L, Gill H , Granfeld t H , et al. Su p erficial and d eep sternal
w ou nd com p lications: incid ence, risk factors and m ortality. Eur J Car-
■ CONCLUSION
diothorac Surg 2001;20(6):1168–1175.
25. Christie JD, Kotloff RM, Ahya VN , et al. The effect of p rim ary graft
d ysfu nction on survival after lu ng transp lantation. Am J Respir Crit
Complications occu r com monly in lung transplant recip i- Care Med 2005;171(11):1312–1316.
ents because of their general d ebilitation and the require- 26. Christie JD, Sager JS, Kim mel SE, et al. Impact of primary graft failure
on outcomes follow ing lung transplantation. Chest 2005;127(1):161–165.
ment for lifelong immunosuppression. Prevention and
27. Gu tierrez CA, Chap arro C, Krajd en M, et al. Cytom egaloviru s virem ia
early recognition of these com plications is im p ortant to pre- in lung transplant recipients receiving ganciclovir and im m une glob-
vent morbid ity and mortality in this high-risk population. u lin. Chest 1998;113(4):924–932.
28. King RC, Binns QA, Rod rigu ez F, et al. Rep erfu sion inju ry signifi- 53. Ailaw ad i G, Lau CL, Sm ith PW, et al. Does rep erfu sion inju ry still
cantly im pacts clinical ou tcom e after p u lm onary transp lantation. Ann cau se significant m ortality after lu ng transplantation? J Thorac Cardio-
Thorac Surg 2000;69(6):1681–1685. vasc Surg 2009;137(3):688–694.
29. Meyers BF, d e la Morena M, Sw eet SC, et al. Prim ary graft d ysfu nction 54. Eriksson LT, Steen S. Ind u ced hyp otherm ia in critical resp iratory fail-
and other selected com p lications of lu ng transp lantation: a single- u re after lu ng transplantation. Ann Thorac Surg 1998;65(3):827–829.
center experience of 983 p atients. J Thorac Cardiovasc Surg 2005;129(6): 55. Van De Wau w er C, Van Raem d onck D, Verled en GM, et al. Risk fac-
1421–1429. tors for airw ay com plications w ithin the first year after lu ng trans-
30. Dau d SA, Yu sen RD, Meyers BF, et al. Im p act of im m ed iate p rim ary plantation. Eur J Cardiothorac Surg 2007;31(4):703–710.
lu ng allograft d ysfu nction on bronchiolitis obliterans synd rom e. Am J 56. Usud a K, Gild ea TR, Pand ya C, et al. Bronchial d ehiscence. J Bronchol
Respir Crit Care Med 2007;175(5):507–513. 2005;12:164–165.
31. Lee JC, Christie JD. Prim ary graft d ysfu nction. Proc Am Thorac Soc 57. Santacru z JF, Mehta AC. Airw ay com p lications and m anagem ent after
2009;6(1):39–46. lung transp lantation: ischem ia, d ehiscence, and stenosis. Proc Am Tho-
32. Whitson BA, N ath DS, Johnson AC, et al. Risk factors for prim ary rac Soc 2009;6(1):79–93.
graft d ysfunction after lu ng transp lantation. J Thorac Cardiovasc Surg 58. King-Biggs MB, Du nitz JM, Park SJ, et al. Airw ay anastom otic d ehis-
2006;131(1):73–80. cence associated w ith u se of sirolim u s im m ed iately after lu ng trans-
33. Matsuzaki Y, Wad d ell TK, Pu skas JD, et al. Am elioration of p ost- p lantation. Transplantation 2003;75(9):1437–1443.
ischem ic lung rep erfu sion inju ry by p rostagland in E1. Am Rev Respir 59. H errera JM, McN eil KD, H iggins RS, et al. Airw ay com p lications after
Dis 1993;148(4 Pt 1):882–889. lu ng transplantation: treatm ent and long-term ou tcom e. Ann Thorac
34. Maccherini M, Keshavjee SH , Slu tsky AS, et al. The effect of low - Surg 2001;71(3):989–993; d iscu ssion 993–994.
p otassiu m -d extran versu s Eu ro-Collins solu tion for p reservation of 60. d e H oyos AL, Patterson GA, Mau rer JR, et al. Pu lm onary transp lanta-
isolated typ e II pneu m ocytes. Transplantation 1991;52(4):621–626. tion. Early and late resu lts. The Toronto Lu ng Transp lant Grou p .
35. Fischer S, Matte-Martyn A, De Perrot M, et al. Low -p otassiu m d extran J Thorac Cardiovasc Surg 1992;103(2):295–306.
preservation solu tion im p roves lu ng fu nction after hu m an lu ng trans- 61. De Gracia J, Cu lebras M, Alvarez A, et al. Bronchoscop ic balloon
plantation. J Thorac Cardiovasc Surg 2001;121(3):594–596. d ilatation in the m anagem ent of bronchial stenosis follow ing lu ng
36. Oto T, Griffiths AP, Rosenfeld t F, et al. Early ou tcom es com paring Per- transplantation. Respir Med 2007;101(1):27–33.
fad ex, Euro-Collins, and Pap w orth solu tions in lu ng transp lantation. 62. Kram er MR, Denning DW, Marshall SE, et al. Ulcerative tracheobron-
Ann Thorac Surg 2006;82(5):1842–1848. chitis after lu ng transp lantation. A new form of invasive asp ergillosis.
37. Stru ber M, Wilhelm i M, H arringer W, et al. Flu sh p erfu sion w ith low Am Rev Respir Dis 1991;144(3 Pt 1):552–556.
potassiu m d extran solu tion im p roves early graft fu nction in clinical 63. N u nley DR, Gal AA, Vega JD, et al. Sap rop hytic fu ngal infections and
lu ng transplantation. Eur J Cardiothorac Surg 2001;19(2):190–194. com plications involving the bronchial anastom osis follow ing hu m an
38. Zahrad nik JM, Ad enoviru s p neu m onia. Semin Respir Infect 1987;2(2): lu ng transplantation. Chest 2002;122(4):1185–1191.
104–111. 64. H ad jiliad is D, H ow ell DN , Davis RD, et al. Anastom otic infections in
39. Yam ashita M, Schm id RA, And o K, et al. N itrop ru ssid e am eliorates lu ng transplant recipients. Ann Transplant 2000;5(3):13–19.
lu ng allograft rep erfu sion inju ry. Ann Thorac Surg 1996;62(3):791–796; 65. Palm er SM, Perfect JR, H ow ell DN , et al. Cand id al anastom otic infec-
d iscussion 796–797. tion in lu ng transp lant recip ients: su ccessfu l treatm ent w ith a com bi-
40. Carter YM, Gelm an AE, Kreisel D. Pathogenesis, m anagem ent, and nation of system ic and inhaled antifu ngal agents. J Heart Lung
consequences of p rim ary graft d ysfu nction. Semin Thorac Cardiovasc Transplant 1998;17(10):1029–1033.
Surg 2008;20(2):165–172. 66. Chap arro C, Kesten S. Infections in lu ng transp lant recip ients. Clin
41. Bhabra MS, H op kinson DN , Shaw TE, et al. Controlled rep erfu sion Chest Med 1997;18(2):339–351.
protects lu ng grafts d u ring a transient early increase in perm eability. 67. Bassiri AG, Girgis RE, Theod ore J. Actinom yces od ontolyticu s thora-
Ann Thorac Surg 1998;65(1):187–192. copu lm onary infections. Tw o cases in lu ng and heart–lu ng transp lant
42. Clark SC, Sud arshan C, Khanna R, et al. Controlled rep erfu sion and recipients and a review of the literatu re. Chest 1996;109(4):1109–1111.
pentoxifylline m od u late rep erfu sion inju ry after single lu ng trans- 68. H u sain S, Chan KM, Palm er SM, et al. Bacterem ia in lu ng transp lant
plantation. J Thorac Cardiovasc Surg 1998;115(6):1335–1341. recip ients in the cu rrent era. Am J Transplant 2006;6(12):3000–3007.
43. Clark SC, Su d arshan CD, Dark JH . Controlled p erfu sion of the trans- 69. Palm er SM, Alexand er BD, Sand ers LL, et al. Significance of blood
planted lu ng. Ann Thorac Surg 2001;71(5):1755–1756. stream infection after lu ng transp lantation: analysis in 176 consecu -
44. Fiser SM, Kron IL, Long SM, et al. Controlled p erfu sion d ecreases tive p atients. Transplantation 2000;69(11):2360–2366.
reperfusion inju ry after high-flow rep erfu sion. J Heart Lung Transplant 70. Ettinger NA, Bailey TC, Trulock EP, et al. Cytomegalovirus infection and
2002;21(6):687–691. pneumonitis. Impact after isolated lung transplantation. Washington Uni-
45. H alld orsson A, Kronon M, Allen BS, et al. Controlled rep erfusion after versity Lung Transplant Group. Am Rev Respir Dis 1993;147(4):1017–1023.
lung ischem ia: im plications for im proved function after lu ng trans- 71. Kru ger RM, Paranjothi S, Storch GA, et al. Im p act of p rop hylaxis w ith
plantation. J Thorac Cardiovasc Surg 1998;115(2):415–424; d iscu ssion cytogam alone on the incid ence of CMV virem ia in CMV-seropositive
424–425. lu ng transp lant recipients. J Heart Lung Transplant 2003;22(7):754–763.
46. H alld orsson AO, Kronon M, Allen BS, et al. Controlled reperfusion 72. Avery RK. Valganciclovir versu s IV ganciclovir for therap y of
prevents p u lm onary inju ry after 24 hou rs of lu ng p reservation. Ann cytom egalovirus virem ia: has victory been achieved ? Am J Transplant
Thorac Surg 1998;66(3):877–884; d iscu ssion 884–885. 2007;7(9):2062–2063.
47. H alld orsson AO, Kronon MT, Allen BS, et al. Low ering reperfusion 73. Zam ora MR. Controversies in lung transplantation: m anagem ent of
pressu re red u ces the inju ry after p u lm onary ischem ia. Ann Thorac cytom egalovirus infections. J Heart Lung Transplant 2002;21(8):841–849.
Surg 2000;69(1):198–203; d iscu ssion 204. 74. Zed tw itz-Liebenstein K, Presterl E, Deviatko E, et al. Acu te renal fail-
48. Lick SD, Brow n PS Jr, Ku ru sz M, et al. Techniqu e of controlled rep er- u re in a lu ng transplant p atient after therap y w ith cid ofovir. Transpl
fusion of the transp lanted lu ng in hu m ans. Ann Thorac Surg 2000; Int 2001;14(6):445–446.
69(3):910–912. 75. Garantziotis S, H ow ell DN , McAd am s H P, et al. Influ enza p neu m onia
49. Date H , Triantafillou AN , Tru lock EP, et al. Inhaled nitric oxid e in lung transplant recipients: clinical features and association w ith
red u ces hu m an lu ng allograft d ysfu nction. J Thorac Cardiovasc Surg bronchiolitis obliterans synd rom e. Chest 2001;119(4):1277–1280.
1996;111(5):913–919. 76. H olt N D, Gou ld FK, Taylor CE, et al. Incid ence and significance of
50. Fiser SM, Cop e JT, Kron IL, et al. Aerosolized p rostacyclin noncytom egaloviru s viral respiratory infection after ad u lt lu ng trans-
(epoprostenol) as an alternative to inhaled nitric oxid e for patients p lantation. J Heart Lung Transplant 1997;16(4):416–419.
w ith rep erfusion inju ry after lu ng transp lantation. J Thorac Cardiovasc 77. Matar LD, McAd am s H P, Palm er SM, et al. Resp iratory viral infec-
Surg 2001;121(5):981–982. tions in lu ng transplant recipients: rad iologic find ings w ith clinical
51. Meyers BF, Su nd t TM 3rd , H enry S, et al. Selective u se of extracorpo- correlation. Radiology 1999;213(3):735–742.
real m em brane oxygenation is w arranted after lu ng transplantation. 78. McCu rd y LH , Milstone A, Du m m er S. Clinical featu res and ou tcom es
J Thorac Cardiovasc Surg 2000;120(1):20–26. of p aram yxoviral infection in lu ng transp lant recip ients treated w ith
52. Fischer S, Bohn D, Rycu s P, et al. Extracorp oreal m em brane oxygena- ribavirin. J Heart Lung Transplant 2003;22(7):745–753.
tion for prim ary graft d ysfu nction after lu ng transplantation: analysis 79. Palmer SM Jr, Henshaw NG, Howell DN, et al. Community respiratory
of the Extracorp oreal Life Su p p ort Organization (ELSO) registry. viral infection in ad u lt lu ng transp lant recip ients. Chest 1998;113(4):
J Heart Lung Transplant 2007;26(5):472–477. 944–950.
80. Wand strat TL. Resp iratory syncytial viru s im m u ne globu lin intra- 109. Wahid i MM, et al. Diagnosis and ou tcom e of early p leu ral sp ace infec-
venou s. Ann Pharmacother 1997;31(1):83–88. tion follow ing lu ng transplantation. Chest 2009;135(2):484–491.
81. Blu m berg EA, Albano C, Pru ett T, et al. The im m u nogenicity of 110. Ju d son MA, H and y JR, Sahn SA. Pleu ral effu sions follow ing lu ng
influ enza virus vaccine in solid organ transp lant recip ients. Clin Infect transplantation. Tim e cou rse, characteristics, and clinical im p lica-
Dis 1996;22(2):295–302. tions. Chest 1996;109(5):1190–1194.
82. Ju rad o M, N avarro JM, H ernánd ez J, et al. Ad enoviru s-associated 111. Chiles C, et al. H eart–lu ng transp lantation: the p ostop erative chest
haem orrhagic cystitis after bone m arrow transp lantation su ccessfu lly rad iograp h. Radiology 1985;154(2):299–304.
treated w ith intravenou s ribavirin. Bone Marrow Transplant 1995;15(4): 112. N u nley DR, et al. Em p yem a com p licating su ccessfu l lu ng transp lan-
651–652. tation. Chest 1999;115(5):1312–1315.
83. Maslo C, Girard PM, Urban T, et al. Ribavirin therap y for ad enoviru s 113. Bittner HB, et al. Hyperacute rejection in single lung transplantation–case
pneumonia in an AIDS patient. Am J Respir Crit Care Med 1997;156(4 Pt 1): report of successful management by means of plasmapheresis and
1263–1264. antithymocyte globulin treatment. Transplantation 2001;71(5):649–651.
84. McCarthy AJ, Bergin M, De Silva LM, et al. Intravenou s ribavirin ther- 114. Choi JK, et al. H yp eracute rejection of a p u lm onary allograft. Im m ed i-
ap y for d issem inated ad enoviru s infection. Pediatr Infect Dis J 1995; ate clinical and p athologic find ings. Am J Respir Crit Care Med 1999;
14(11):1003–1004. 160(3):1015–1018.
85. Shetty AK, Gans H A, So S, et al. Intravenou s ribavirin therap y for 115. Frost AE, Jam m al CT, Cagle PT. H yp eracu te rejection follow ing lu ng
ad enovirus p neum onia. Pediatr Pulmonol 2000;29(1):69–73. transplantation. Chest 1996;110(2):559–562.
86. The MIST (Managem ent of Influ enza in the Sou thern H em isp here Tri- 116. Saint Martin GA, et al. H u m oral (antibod y-m ed iated ) rejection in
alists) Stud y Grou p. Rand om ised trial of efficacy and safety of inhaled lu ng transp lantation. J Heart Lung Transplant 1996;15(12):1217–1222.
zanam ivir in treatm ent of influ enza A and B viru s infections. Lancet 117. Lau CL, et al. Influ ence of p anel-reactive antibod ies on p osttransp lant
1998;352(9144):1877–1881. ou tcom es in lu ng transp lant recip ients. Ann Thorac Surg 2000;69(5):
87. Cox N J, Su bbarao K. Influ enza. Lancet 1999;354(9186):1277–1282. 1520–1524.
88. Dengler TJ, Strnad N, Bühring I, et al. Differential immune response to 118. Magro CM, et al. H u m orally m ed iated p osttransp lantation sep tal cap -
influenza and pneumococcal vaccination in immunosuppressed patients illary injury synd rom e as a com m on form of pulm onary allograft
after heart transplantation. Transplantation 1998;66(10):1340–1347. rejection: a hypothesis. Transplantation 2002;74(9):1273–1280.
89. Grossi P, Farina C, Fiocchi R, et al. Prevalence and outcome of invasive 119. H opkins PM, et al. Prospective analysis of 1,235 transbronchial lu ng
fungal infections in 1,963 thoracic organ transplant recipients: a multicen- biop sies in lung transp lant recip ients. J Heart Lung Transplant 2002;
ter retrospective study. Italian Study Group of Fungal Infections in Tho- 21(10):1062–1067.
racic Organ Transplant Recipients. Transplantation 2000;70(1):112–116. 120. H u sain AN , et al. Analysis of risk factors for the d evelop m ent of bron-
90. Sole A, Salavert M. Fu ngal infections after lu ng transp lantation. Curr chiolitis obliterans synd rom e. Am J Respir Crit Care Med 1999;159(3):
Opin Pulm Med 2009;15(3):243–253. 829–833.
91. Rem und KF, Best M, Egan JJ. Infections relevant to lu ng transp lanta- 121. Berry GJ, et al. A w orking form u lation for the stand ard ization of
tion. Proc Am Thorac Soc 2009;6(1):94–100. nom enclatu re in the d iagnosis of heart and lung rejection: Lu ng Rejec-
92. Kanj SS, Welty-Wolf K, Mad d en J, et al. Fu ngal infections in lu ng and tion Stu d y Grou p. The International Society for H eart Transp lanta-
heart–lung transp lant recip ients. Rep ort of 9 cases and review of the tion. J Heart Transplant 1990;9(6):593–601.
literatu re. Medicine (Baltimore) 1996;75(3):142–156. 122. Yousem SA, et al. Revision of the 1990 w orking form u lation for the
93. Mehrad B, Paciocco G, Martinez FJ, et al. Sp ectru m of Aspergillus classification of pu lm onary allograft rejection: Lung Rejection Stud y
infection in lung transplant recipients: case series and review of the Grou p. J Heart Lung Transplant 1996;15(1 Pt 1):1–15.
literatu re. Chest 2001;119(1):169–175. 123. Sharples LD, et al. Risk factors for bronchiolitis obliterans: a system -
94. Westney GE, Kesten S, De H oyos A, et al. Aspergillus infection in sin- atic review of recent p u blications. J Heart Lung Transplant 2002;21(2):
gle and d ou ble lu ng transp lant recip ients. Transplantation 1996;61(6): 271–281.
915–919. 124. H igenbottam T, et al. Transbronchial lu ng biop sy for the d iagnosis of
95. H ad jiliad is D, Sporn TA, Perfect JR, et al. Ou tcom e of lu ng transp lan- rejection in heart–lu ng transp lant p atients. Transplantation 1988;46(4):
tation in p atients w ith m ycetom as. Chest 2002;121(1):128–134. 532–539.
96. N u nley DR, Ohori P, Grgu rich WF, et al. Pu lm onary asp ergillosis in 125. Tru lock EP, et al. The role of transbronchial lu ng biop sy in the treat-
cystic fibrosis lung transp lant recip ients. Chest 1998;114(5):1321–1329. m ent of lung transp lant recip ients. An analysis of 200 consecu tive
97. H u sain S, McCu rry K, Dau ber J, et al. Nocardia infection in lung trans- p roced u res. Chest 1992;102(4):1049–1054.
p lant recipients. J Heart Lung Transplant 2002;21(3):354–359. 126. Baz MA, et al. Diagnostic yield of bronchoscop ies after isolated lu ng
98. Palm er SM Jr, Kanj SS, Davis RD, et al. A case of d issem inated infec- transp lantation. Chest 1996;110(1):84–88.
tion w ith Nocardia brasiliensis in a lu ng transp lant recip ient. Transplan- 127. Boehler A, et al. Prosp ective stu d y of the valu e of transbronchial lu ng
tation 1997;63(8):1189–1190. biop sy after lung transp lantation. Eur Respir J 1996;9(4):658–662.
99. Raj R, Frost AE. Scedosporium apiospermum fu ngem ia in a lu ng trans- 128. Guilinger RA, et al. The im p ortance of bronchoscop y w ith trans-
p lant recipient. Chest 2002;121(5):1714–1716. bronchial biop sy and bronchoalveolar lavage in the m anagem ent of
100. Calvo V, Borro JM, Morales P, et al. Antifu ngal p rop hylaxis d u ring the lu ng transp lant recip ients. Am J Respir Crit Care Med 1995;152(6 Pt 1):
early p ostop erative p eriod of lu ng transp lantation. Valencia Lu ng 2037–2043.
Transp lant Group . Chest 1999;115(5):1301–1304. 129. Sibley RK, et al. The role of transbronchial biop sies in the m anage-
101. Erjavec Z, et al. Tolerance and efficacy of Am p hotericin B inhalations m ent of lu ng transplant recip ients. J Heart Lung Transplant 1993;12(2):
for prevention of invasive p ulm onary aspergillosis in haem atological 308–324.
p atients. Eur J Clin Microbiol Infect Dis 1997;16(5):364–368. 130. Tam m M, et al. Bronchiolitis obliterans synd rom e in heart–lu ng trans-
102. Palm er SM, et al. Safety of aerosolized am p hotericin B lip id com p lex plantation: surveillance biopsies. Am J Respir Crit Care Med 1997;155(5):
in lung transplant recip ients. Transplantation 2001;72(3):545–548. 1705–1710.
103. Yonan N A, et al. Single lu ng transp lantation for em p hysem a: p red ic- 131. Valentine VG, et al. Su ccess of lu ng transp lantation w ithou t su rveil-
tors for native lu ng hyp erinflation. J Heart Lung Transplant 1998;17(2): lance bronchoscop y. J Heart Lung Transplant 2002;21(3):319–326.
192–201. 132. Brock MV, et al. Ind uction therap y in lu ng transp lantation: a p rosp ec-
104. Angles R, et al. Lung transp lantation for em p hysem a. Lu ng hyperin- tive, controlled clinical trial com p aring OKT3, anti-thym ocyte globu -
flation: incid ence and ou tcom e. Transpl Int 2005;17(12):810–814. lin, and d aclizu m ab. J Heart Lung Transplant 2001;20(12):1282–1290.
105. Weill D, et al. Acu te native lu ng hyp erinflation is not associated w ith 133. Trulock EP. Lung transplantation. Am J Respir Crit Care Med 1997;155(3):
p oor outcom es after single lu ng transp lant for em p hysem a. J Heart 789–818.
Lung Transplant 1999;18(11):1080–1087. 134. H orning N R, et al. Tacrolim u s therap y for p ersistent or recu rrent
106. Kozow er BD, et al. Potential for d etrim ental hyp erinflation after lu ng acu te rejection after lu ng transp lantation. J Heart Lung Transplant 1998;
transplantation w ith ap plication of negative pleu ral pressure to 17(8):761–767.
u nd ersized lung grafts. J Thorac Cardiovasc Surg 2003;125(2):430–432. 135. Vitulo P, et al. Efficacy of tacrolim u s rescu e therap y in refractory acu te
107. Ferrer J, et al. Acu te and chronic p leu ral com p lications in lu ng trans- rejection after lu ng transp lantation. J Heart Lung Transplant 2002;21(4):
p lantation. J Heart Lung Transplant 2003;22(11):1217–1225. 435–439.
108. H errid ge MS, et al. Pleu ral com p lications in lu ng transp lant recip i- 136. H ong JC, Kahan BD. Sirolim u s rescu e therap y for refractory rejection
ents. J Thorac Cardiovasc Surg 1995;110(1):22–26. in renal transplantation. Transplantation 2001;71(11):1579–1584.
137. Kahan BD. Efficacy of sirolim u s com pared w ith azathioprine for 162. Schaar CG, et al. Su ccessfu l ou tcom e w ith a “qu intu p le ap p roach” of
red u ction of acute renal allograft rejection: a rand om ised m u lticentre posttransplant lym phoproliferative disorder. Transplantation 2001;71(1):
stu d y. The Rapam u ne US Stu d y Grou p . Lancet 2000;356(9225): 47–52.
194–202. 163. Sw erd low SH . Classification of the p osttransp lant lym p hop rolifera-
138. Snell GI, et al. Rescu e therap y: a role for sirolim u s in lu ng and heart tive d isord ers: from the p ast to the p resent. Semin Diagn Pathol 1997;
transplant recipients. Transplant Proc 2001;33(1/ 2):1084–1085. 14(1):2–7.
139. William s JW, et al. Exp eriences w ith leflu nom id e in solid organ trans- 164. Montone KT, et al. Analysis of Ep stein–Barr viru s-associated p ost-
p lantation. Transplantation 2002;73(3):358–366. transp lantation lym p hop roliferative d isord er after lu ng transp lanta-
140. Chakinala MM, Tru lock EP. Acu te allograft rejection after lu ng trans- tion. Surgery 1996;119(5):544–551.
p lantation: d iagnosis and therap y. Chest Surg Clin N Am 2003;13(3): 165. Wigle DA, et al. Epstein–Barr viru s serology and p osttransp lant lym -
525–542. p hop roliferative d isease in lu ng transp lantation. Transplantation
141. Coop er JD, et al. A w orking form u lation for the stand ard ization of 2001;72(11):1783–1786.
nom enclature and for clinical staging of chronic d ysfunction in lung 166. Wood BL, et al. The recip ient origin of p osttransp lant lym p hop rolifer-
allografts. International Society for H eart and Lu ng Transplantation. J ative d isord ers in p ulm onary transp lant p atients. A rep ort of three
Heart Lung Transplant 1993;12(5):713–716. cases. Cancer 1996;78(10):2223–2228.
142. Estenne M, H ertz MI. Bronchiolitis obliterans after hu m an lu ng trans- 167. Sw innen LJ, et al. Increased incid ence of lym p hop roliferative d isord er
p lantation. Am J Respir Crit Care Med 2002;166(4):440–444. after im m unosu pp ression w ith the m onoclonal antibod y OKT3 in car-
143. H ertz MI, et al. The registry of the international society for heart and d iac-transp lant recip ients. N Engl J Med 1990;323(25):1723–1728.
lung transplantation: nineteenth official rep ort—2002. J Heart Lung 168. Walker RC, et al. Pretransp lantation assessm ent of the risk of lym p ho-
Transplant 2002;21(9):950–970. p roliferative d isord er. Clin Infect Dis 1995;20(5):1346–1353.
144. Meyers BF, et al. Lu ng transp lantation: a d ecad e of experience. Ann 169. H achem RR, et al. Abd om inal-p elvic lym p hop roliferative d isease
Surg 1999;230(3):362–370; d iscu ssion 370–371. after lu ng transplantation: p resentation and ou tcom e. Transplantation
145. Estenne M, et al. Bronchiolitis obliterans synd rom e 2001: an up d ate of 2004;77(3):431–437.
the d iagnostic criteria. J Heart Lung Transplant 2002;21(3):297–310. 170. Verschu u ren EA, et al. Treatm ent of p osttransp lant lym p hop rolifera-
146. Davis RD Jr, et al. Im p roved lu ng allograft fu nction after fu nd op lica- tive d isease w ith ritu xim ab: the rem ission, the relap se, and the com -
tion in patients w ith gastroesophageal reflu x d isease u nd ergoing lung p lication. Transplantation 2002;73(1):100–104.
transplantation. J Thorac Cardiovasc Surg 2003;125(3):533–542. 171. Knoop C, et al. Post-transp lant lym p hop roliferative d isord ers after
147. H ennessy SA, Sw enson BR, Kozow er BD, et al. Donor hyp eroxia is lung transplantation: first-line treatm ent w ith rituxim ab m ay ind u ce
associated w ith d evelop m ent of bronchiolitis obliterans follow ing com p lete rem ission. Clin Transplant 2006;20(2):179–187.
lu ng transp lantation. Presented at the 56th Annu al Meeting of Sou th- 172. Malou f MA, et al. Anti-viral p rop hylaxis red u ces the incid ence of
ern Thoracic Su rgical Association, Marco Island , FL, N ovem ber 4–7, lym p hop roliferative d isease in lu ng transp lant recip ients. J Heart
2009. Lung Transplant 2002;21(5):547–554.
148. Belp erio JA, et al. Chronic lu ng allograft rejection: m echanism s and 173. N ielsen TD, et al. Atrial fibrillation after p u lm onary transp lant. Chest
therap y. Proc Am Thorac Soc 2009;6(1):108–121. 2004;126(2):496–500.
149. Lu betkin EI, et al. GI com p lications after orthotop ic lu ng transplanta- 174. Kogan A, et al. Atrial fibrillation after ad u lt lu ng transp lantation.
tion. Am J Gastroenterol 1996;91(11):2382–2390. Transplant Proc 2003;35(2):679.
150. Bravo C, et al. Prevalence and m anagem ent of gastrointestinal com - 175. Mason DP, et al. Atrial fibrillation after lu ng transp lantation: tim ing,
plications in lung transp lant p atients: MITOS stu d y group . Transplant risk factors, and treatm ent. Ann Thorac Surg 2007;84(6):1878–1884.
Proc 2007;39(7):2409–2412. 176. Aranki SF, et al. Pred ictors of atrial fibrillation after coronary artery
151. Hoekstra HJ, et al. Gastrointestinal complications in lung transplant sur- su rgery. Cu rrent trend s and im p act on hosp ital resou rces. Circulation
vivors that require surgical intervention. Br J Surg 2001;88(3):433–438. 1996;94(3):390–397.
152. Gilljam M, et al. GI com p lications after lu ng transp lantation in 177. Roselli EE, et al. Atrial fibrillation com p licating lu ng cancer resection.
patients w ith cystic fibrosis. Chest 2003;123(1):37–41. J Thorac Cardiovasc Surg 2005;130(2):438–444.
153. Pollard TR, et al. Abd om inal op erations after lu ng transp lantation. 178. Lau CL, Tru lock E, Gu thrie T. Post-op erative atrial d ysrhythm ias after
Ind ications and ou tcom e. Arch Surg 1997;132(7):714–717; d iscu ssion lu ng transplantation. J Heart Lung Transplant 2004;23:150A.
717–718. 179. Ishani A, et al. Pred ictors of renal fu nction follow ing lu ng or
154. Robertson AG, et al. A call for standardization of antireflux surgery in the heart–lu ng transp lantation. Kidney Int 2002;61(6):2228–2234.
lung transplantation population. Transplantation 2009;87(8):1112–1114. 180. Mason DP, et al. Dialysis after lu ng transp lantation: p revalence, risk
155. Cantu E III, et al. J. Maxw ell Cham berlain Mem orial Pap er. Early fun- factors and ou tcom e. J Heart Lung Transplant 2007;26(11):1155–1162.
d op lication prevents chronic allograft d ysfu nction in patients w ith 181. Soccal PM, et al. Im provem ent of d ru g-ind u ced chronic renal failu re
gastroesophageal reflux d isease. Ann Thorac Surg 2004;78(4):1142–1151; in lung transplantation. Transplantation 1999;68(1):164–165.
d iscu ssion 1142–1151. 182. Broekroelofs J, et al. Long-term renal ou tcom e after lu ng transp lanta-
156. Aris RM, et al. Post-transp lantation lym p hop roliferative d isord er in tion is p red icted by the 1-m onth p ostop erative renal fu nction loss.
the Epstein–Barr viru s-naive lu ng transp lant recip ient. Am J Respir Transplantation 2000;69(8):1624–1628.
Crit Care Med 1996;154(6 Pt 1):1712–1717. 183. Lichtenstein GR, et al. Fatal hyp eram m onem ia follow ing orthotop ic
157. Arm itage JM, et al. Posttransp lant lym p hop roliferative d isease in tho- lung transplantation. Gastroenterology 1997;112(1):236–240.
racic organ transplant patients: ten years of cyclosporine-based 184. Lichtenstein GR, et al. Fatal hyp eram m onem ia after orthotop ic lu ng
im m u nosup pression. J Heart Lung Transplant 1991;10(6):877–886; d is- transplantation. Ann Intern Med 2000;132(4):283–287.
cussion 886–887. 185. Tu chm an M, et al. H ep atic glu tam ine synthetase d eficiency in fatal
158. Levine SM, et al. A low incid ence of posttransplant lymphoproliferative hyp eram m onem ia after lu ng transp lantation. Ann Intern Med 1997;
disord er in 109 lung transplant recipients. Chest 1999;116(5):1273–1277. 127(6):446–449.
159. Paranjothi S, et al. Lym p hop roliferative d isease after lu ng transp lan- 186. Berry GT, et al. Su ccessfu l u se of alternate w aste nitrogen agents and
tation: com p arison of presentation and outcom e of early and late hem od ialysis in a patient w ith hyperam m onem ic com a after heart–
cases. J Heart Lung Transplant 2001;20(10):1054–1063. lung transp lantation. Arch Neurol 1999;56(4):481–484.
160. Angel LF, et al. Posttransp lant lym p hop roliferative d isord ers in lu ng 187. Singh N , Gayow ski T, Marino IR. H em olytic u rem ic synd rom e in
transplant recip ients: clinical exp erience at a single center. Ann Trans- solid -organ transplant recip ients. Transpl Int 1996;9(1):68–75.
plant 2000;5(3):26–30. 188. H achem RR, et al. Throm botic m icroangiop athy after lu ng transp lan-
161. Dharnid harka VR, et al. Post-transp lant lym p hop roliferative d isord er tation. Transplantation 2006;81(1):57–63.
in the United States: you ng Cau casian m ales are at highest risk. Am J 189. George JN . H ow I treat p atients w ith throm botic throm bocytop enic
Transplant 2002;2(10):993–998. p u rp u ra–hem olytic urem ic synd rom e. Blood 2000;96(4):1223–1229.
CHAPTER
51
Complications Following
Heart Transplantation
Sanjeev Aggarwal and Francis D. Pagani
■ INTRODUCTION long-term m echanical circulatory supp ort as an im portant

treatm ent op tion for p atients su ffering from ad vanced
The incid ence and p revalence of heart failu re continu e to heart failu re. Ventricu lar assist d evice therap y has been
rise, p resently affecting over 5 m illion p eop le, w ith over u sed su ccessfu lly as a brid ge to transp lantation as w ell as
500,000 new cases d iagnosed annu ally in the United for perm anent or “d estination therapy” for patients w ho
States (1). H eart transp lantation rem ains the gold stan- are not transp lant eligible (6–9).
d ard for card iac rep lacem ent therap y and rep resents the A tem p oral p attern for the d evelop m ent of sp ecific
m ost su ccessfu l long-term treatm ent op tion available for com p lications follow ing heart transp lantation is w ell rec-
p atients w ith end -stage heart d isease. Desp ite its su ccess ognized (Fig. 51.2) (2). Com p lications contribu ting d irectly
in im p roving both su rvival and qu ality of life for p atients to early m ortality and m orbid ity w ithin the first 30 d ays
w ith refractory congestive heart failu re, heart transp lan- follow ing heart transp lantation are generally d u e to p ri-
tation is associated w ith significant early and long-term m ary allograft failu re and , to a lesser extent, infection and
m orbid ity and m ortality. In d eterm ining su itability for allograft rejection. Within the first year, infection and com -
transp lantation, the p otential su rvival and qu ality-of-life p lications of acu te allograft rejection d om inate cau ses of
benefit m u st be w eighed against the p otential short- and mortality and m orbid ity. After the first year, the d evelop-
long-term m orbid ity and m ortality associated w ith heart ment of card iac allograft vascu lop athy and post-transplant
transp lantation. lym p hop roliferative d isord ers becom e significant cau ses
The overall exp ected 1-year su rvival for all patients fol- of m ortality, w ith infectiou s cau ses con tribu ting to a
low ing heart transp lantation is approxim ately 82% (2). lesser extent. Other long-term com p lications of transp lan-
Registry d ata from the International Society for H eart and tation that contribu te to late m orbid ity and ad versely
Lu ng Transp lantation (ISH LT) show im p rovem ents in su r- im p act qu ality of life inclu d e the d evelop m ent of renal
vival w hen ou tcom es are stratified by era. In the m ost insu fficiency, hyp ertension, and end ocrine and m etabolic
recent era (2002 to 2007), expected 1-year survival for all abnorm alities (i.e., d iabetes m ellitu s, osteop orosis, and
p atients is 86%. Fifty percent of heart transplant recip ients hyp erlipid em ia).
survive ap p roxim ately 10 years. There is a linear attrition
rate of 4% p er year, w hich has not changed d ram atically
over the p ast several years, ow ing to problem s su ch as
■ COMPLICATIONS IN THE EARLY
coronary allograft vascu lop athy and late allograft rejection PERIOPERATIVE PERIOD
and failu re (Fig. 51.1) (2–5). ■ Acute allograft failure
Desp ite the clinical su ccesses w ith card iac transp lanta-
tion, lim itations in d onor availability have m ad e this ther- Acu te allograft failure follow ing card iac transplantation
ap y a treatm ent op tion for only a sm all fraction of p atients represents the m ost comm on cau se of m ortality w ithin the
suffering from end -stage heart failu re. The total volu m e of first 30 d ays, accou nting for 41% of early d eaths (Fig. 51.3)
transplants being perform ed w orld w id e has rem ained (2,10–12). The incid ence of acu te allograft failure has
static over the p ast d ecad e, w ith a slight d ecrease in vol- remained relatively constant over the p ast 10 years,
u m es in recent years. Prolonged w aiting tim es and lim ita- betw een 2% and 5% in m ost large series (2,3,11). Mu ltiple
tions in the d onor pool have led to the em ergence of recipient and d onor characteristics that ad versely influence
the incid ence of acute allograft failu re have been reported
(Table 51.1) (11,13).
Sanjeev Aggarwal: Mid Am erica H eart and Vascu lar Insti- The etiology for acu te allograft failu re follow ing heart
tu te, Saint Luke’s H osp ital of Kansas City, Kansas City, MO tran sp lan tation is p red om inantly d u e to right-sid ed cir-
64111. cu latory failu re. This can be a consequ ence of either ele-
Francis D. Pagani: Section of Card iac Su rgery, Departm ent vated recip ient p u lm onary vascu lar resistance or intrinsic
of Su rgery, University of Michigan H ealth System s, Ann d onor right ventricu lar contractile d ysfu nction second ary
Arbor, MI 48109. to brain death, myocardial contusion (i.e., cardiopulm onary
674
Chapter 51 • Complications Following Heart Transplantation 675
FIGURE 51.1. Heart transplant survival for adult and pediatric heart transplants performed between J anuary 1982 and J une
2007. (Data obtained from the Registry of the International Society for Heart and Lung Transplantation—2009). (Reprinted from
Taylor DO, Stehlik J , Edwards LB, et al. Registry of the International Society for Heart and Lung Transplantation: twenty-sixth
official adult heart transplant report—2009. J Heart Lung Transplant 2009;28(10):1011 (Fig. 6).)
resu scitation or blunt thoracic traum a), or ischem ic inju ry d ial p rotection or p rolonged allograft ischem ic time. For
(14–16). Preoperative elevation of recipient pulmonary vas- allograft isch em ic tim es greater th an ap p roxim ately
cular resistance has been id entified as an ind epend ent pre- 2 hou rs, there is an increasing risk of d eath from allograft
d ictor for early mortality and correlates in a linear fashion failu re (Fig. 51.5) (2). When stratified by recipient age,
w ith mortality follow ing heart transplantation (Fig. 51.4) the effect of d onor heart ischem ia tim e is m ost p ronou nced
(2,5, 17–19). in old er-aged cohorts (2). More u nu su al is acute allograft
Acute allograft failure may also manifest as biventricular failu re second ary to accelerated or hyp eracute rejection.
dysfunction. This can be the result of ischemia–reperfusion In som e instances, the cau se of allograft failu re rem ains
injury to the d onor organ second ary to inad equ ate m yocar- u nexp lained .
50 CAV Acute rejection

Malignancy (non-lymph/PTLD) Graft failure
Infection (non-CMV)
40
Deaths (%)
30
20
10
0
0–30 days 31 days– >1 year– >3 years– >5 years– >10 years
(N = 3,531) 1 year 3 years 5 years 10 years (N = 3,677)
(N = 3,513) (N = 2,716) (N = 2,356) (N = 5,335)
FIGURE 51.2. Causes of death by time following heart transplantation. CAV, cardiac allograft vasculopathy; PTLD, post-transplant
lymphoproliferative disease; CMV, cytomegalovirus; NS, nonspecific. (Reprinted from Taylor DO, Stehlik J , Edwards LB, et al. Registry
of the International Society for Heart and Lung Transplantation: twenty-sixth official adult heart transplant report—2009. J Heart Lung
Transplant 2009;28(10):1018 (Fig. 12).)
Table 5 1 .1 Risk fa ct or s for ea r ly a cu t e

a llogr a ft fa ilu r e
Recipient Factors
Congenital etiology
Higher serum creatinine at transplant
Pulmonary vascular resistance
Mean right atrial pressure
Panel reactive antibody screen value 10%
Previous sternotomy
1 Previous sternotomy
Ventilator
Days on ventricular assist device
Donor Factors
Older donor age
Abnormal echo
FIGURE 51.3. Hazard functions for the specific causes of death during the Diabetes
first 4 months following heart transplantation. (Reprinted from Kirklin J K,
Naftel DC, Bourge RC, et al. Evolving trends in risk profiles and causes of
Longer ischemic time
death after heart transplantation: a ten-year multi-institutional study. J Thorac
Cardiovasc Surg 2003;125(4):883 (Fig. 2A).) Adapted from Young JB, Naftel DC, Ewald G, et al. Determinants of early graft fail-
ure following cardiac transplantation, a 10-year, multi-institutional, multivariable
analysis. J Heart Lung Transplant 2001;20(2):212 (abstract) and Naftel DC, Brown
RN. Survival after heart transplantation. In: Kirklin JK, Young JB, McGiffin DC, eds.
Heart transplantation: Medicine, surgery, immunology, and research. New York,
■ Arrhythmias NY: Churchill Livingstone; 2002:597 (Table 16–6).
Patients can su ffer from variou s rhythm d isord ers follow -

ing card iac transp lantation. Brad ycard ia follow ing trans-
p lant is m ost com m only the resu lt of transient sinu s nod e
d ysfu nction. This can be the resu lt of p rolonged allograft requ ires p acem aker imp lantation. Brad ycard ia occurring
ischem ic tim e, inad equ ate m yocard ial p reservation, su rgi- late is u ncom m on, bu t rep resents an ad verse p rognostic
cal trau m a, card iac d enervation, and intrinsic d onor sinu s sign.
nod e d ysfu nction (20,21). Clinically, brad ycard ia second - Early treatment of symptomatic brad ycard ia d ue to sinus
ary to sinu s nod e d ysfu nction is u su ally asym p tom atic nod e d ysfunction may includ e tem porary external pacing,
and self-lim iting, w ith resolu tion seen in 75% of p atients ad m inistration of beta-ad renergic agents, or treatm ent
by 3 m onths and 90% of patients at 1 year post-transp lant with aminophylline. Permanent pacemaker implantation is
(20). Brad yarrhythm ia second ary to atrioventricular block, required for brad ycardia second ary to sinus nod e dysfunc-
w hile less com m on, is m ore likely to be perm anent and tion that rem ains persistent and symptomatic. The incid ence
FIGURE 51.4. Actuarial survival for heart Kaplan–Meier survival by PVR (Transplants: 1/2002–6/2007)
transplants performed between J anuary 2002
and J une 2007 categorized by pulmonary vas- 100
cular resistance (Wood units). (Data obtained 1-<3 Wood units (N = 5,373) 3-<5 Wood units (N = 1,585)
from the Registry of the International Society 5+ Wood units (N = 548)
for Heart and Lung Transplantation—2009.) 90
(Reprinted from www.ishlt.org/registries/;
adult heart transplant slide set, no. 28. J Heart
Survival (%)
Lung Transplant 2009:28:989–1049.) 80
70
60
1-<3 vs. 3-<5: p =0.0018;
1-<3 vs. 5+: p =0.0180; 3-<5 vs. 5+: p = 0.7697
50
0 1 2 3 4 5
Years
FIGURE 51.5. Actuarial survival for heart transplants performed

between April 1994 and J une 2001 categorized by allograft ischemic time.
(Reprinted from Taylor DO, Edwards LB, Mohacsi PJ , et al. The Registry of
the International Society for Heart and Lung Transplantation: twentieth
official adult heart transplant report—2003. J Heart Lung Transplant
2003;22(6):620 (Fig. 12).)
of perm anent pacem aker implantation follow ing heart h ave in clu d ed atrial th rom bosis at th e su tu re lin e
transplantation is approximately 8% to 10% in most contem- (36,37), atrial d istortion w ith su bsequ ent atrioventricu lar
porary series (22–24). There d oes not appear to be any valvu lar incom p etence (38,39), acqu ired cor-triatriatu m
adverse impact on long-term outcomes in patients requiring w ith m itral inflow obstru ction (40,41), p u lm onary artery
pacemaker placement following transplant (23,25). The anastom otic d istortion (42), chronotrop ic insu fficiency or
reported incid ence of permanent pacemaker implantation heart block (43), and aneu rysm of the ascend ing aorta
follow ing heart transplantation is strongly influenced by (44). Minim izing the am ou nt of resid u al recip ient left
surgical technique and is significantly less w hen bicaval atriu m , p rop er alignm ent of the aortic and p u lm onary
anastomosis rather then biatrial technique is utilized anastom oses, u se of the bicaval techniqu e, and ensu ring
(23,26–28). Since the introd uction of the technique of bicaval ap p osition of recip ient end otheliu m to d onor end othe-
anastomosis, early sinus nod e dysfunction and the need for liu m d u ring creation of the atrial anastom osis can signifi-
permanent pacemaker implantation have been significantly cantly red u ce these technical p itfalls.
reduced . Recently, some authors have reported a decreased Several rep orts have com p ared the techniqu es of bia-
incidence of pacemaker implantation utilizing modifications trial versu s bicaval orthotop ic im p lantation. The biatrial
in the biatrial technique w ith improved methods of sinus techniqu e of heart transp lantation w as originally d escribed
node preservation (29). Other clinical predictors of the need by Low er et al. in the early 1960s (45). This technique has
for pacemaker insertion for symptomatic brad yarrhythmias been u sed w ith su ccess for m any years. Concerns w ith the
includ e increasing d onor and recipient age (22). u se of the biatrial techniqu e have inclu d ed atrial enlarge-
Tachyarrhythmias follow ing heart transplant are most m ent w ith im p aired atrial fu nction, throm bu s form ation,
commonly supraventricular in origin. The overall incid ence sinu s nod e d ysfu nction requ iring p erm anent p acem aker
of atrial arrhythmias is high w ith atrial flutter being the m ost im p lantation, and the d evelop m ent of tricuspid valve
common atrial arrhythmia reported (30–33). A relationship insu fficiency. This led to the introd u ction of the bicaval
between atrial arrhythmias and early allograft rejection and techniqu e of im p lantation in the m id -1990s (46). Several
subsequent late allograft vasculopathy has also been stu d ies have d em onstrated ad vantages of the bicaval tech-
reported , but this observation remains controversial (30,34). niqu e, inclu d ing im p roved p eriop erative hem od ynam ics
An association betw een atrial arrhythmias and an increased and atrial fu nction (28,47), d ecreased arrhythm ias and
risk of long-term mortality has also been reported (35). need for p acem aker im p lantation (27,48,49), and red u ced
The occu rrence of ventricu lar arrhythm ias early follow - tricu sp id regu rgitation (50–52). Since its introd uction, the
ing heart transplantation is unusual and m ay represent ad op tion of the bicaval techniqu e has becom e m ore w id e-
ischem ic allograft injury, electrolyte im balance, or signifi- sp read and now rep resents the m ost com m on techniqu e
cant allograft rejection. Late ventricu lar arrhythm ias may u sed (48). The effect of biatrial versu s bicaval im plantation
occu r in association w ith allograft ischem ia second ary to on long-term ou tcom es is less clear. Althou gh som e early
coronary artery vascu lopathy and represents a p oor prog- single-institu tion series d id show a su rvival benefit w ith
nostic sign. the bicaval m ethod (26,53), m ore contem p orary series have
not show n a significant survival d ifference w ith either tech-
niqu e (48,54).
■ Technical factors Tricu sp id regu rgitation in the card iac allograft rep re-
Alth ou gh tech n ical com p lication s d irectly related to th e sents the m ost com m on valvu lar abnorm ality follow ing
op erative p roced u re are u n u su al, th ey still h ave a sig- heart transp lant. The incid ence rep orted is variable, being
n ifican t im p act on early p ostop erative m orbid ity an d as high as over 80% in som e series, d ep end ing on the clas-
m ortality. Com p lication s related to op erative tech n iqu e sification u sed (55). Risk factors for the d evelop m ent of
tricu sp id regu rgitation inclu d e total nu m ber of end om y- Table 5 1 .2 Risk fa ct or s for occu r r en ce of ca r d ia c
ocard ial biop sies p erform ed , biatrial su rgical techniqu e, a llogr a ft r eject ion
early allograft rejection, and preoperative elevation in
recipient p u lm onary vascu lar resistance (52). Patients su f- Factors Influencing Earlier Initial Rejection Following
fering from severe tricu sp id regu rgitation follow ing trans- Heart Transplantation
plant have been show n to be at increased risk of renal Younger age (among adult recipients)
im pairm ent, right ventricular d ysfu nction, and ad verse Female gender (donor and recipient)
If white recipient: higher number of HLA mismatches
long-term ou tcom es (56). Prop hylactic tricu spid valve
Black recipient race
annu lop lasty at the tim e of im plantation has been show n to
d ecrease the incid ence of regurgitation both in the periop - Risk Factors for Increased Cumulative Number of Rejection
erative period and in the long term and has becom e stan- Episodes During First Year Following Heart Transplantation
Younger age of recipient
d ard p ractice in m any centers (51,57).
Female gender (donor and recipient)
HLA–DR mismatches
■ COMPLICATIONS IN THE FIRST YEAR Induction therapy (i.e., OKT3 therapy)
Risk Factors for Recurrent Rejection Episodes During the
■ Cardiac allograft rejection First Year Following Heart Transplantation
Acu te allograft rejection rem ains a significant cau se of m or- Female gender (donor and recipient)
tality and m orbid ity follow ing heart transp lantation w ithin Younger recipient age (except infant)
Positive CMVserology before transplant
the first year, accou nting for u p to 20% of early d eaths (Fig.
Induction therapy (i.e., OKT3 therapy)
51.2) (2,58,59). Ap p roxim ately 60% of ad u lt transp lant
Fewer months since transplant
recip ients w ill exp erience one or m ore ep isod es of acu te Fewer months since last rejection
allograft rejection w ithin 6 m onths follow ing heart trans- Greater number of previous infections
plantation, w hile ap proxim ately one-third of p atients Increased donor ischemic time
rem ain free of allograft rejection at 1 year (Fig. 51.6) (60).
Approxim ately 25% of p atients w ill experience another Adapted from Jarcho J, Naftel DC, Shroyer TW, et al. Influence of HLA mismatch
episod e of acu te allograft rejection w ithin 1 m onth of the on rejection after heart transplantation: a multiinstitutional study. The Cardiac
Transplant Research Database Group. J Heart Lung Transplant 1994;13(4):583–595;
previou s ep isod e. The greatest risk for recurrence of allo-
discussion 595–596 and Kubo SH, Naftel DC, Mills RM Jr, et al. Risks factors for
graft rejection is w ithin 1 m onth of the p reviou s rejection late recurrent rejection after heart transplantation: a multiinstitutional, multivari-
episod e (60). Beyond 1 year, there is a significant d ecrease able analysis. Cardiac Transplant Research Database Group. J Heart Lung Trans-
in num ber of ep isod es of acu te allograft rejection (61). plant 1995;14(3):409–418.
Patients exp eriencing late episod es of acu te allograft rejec-
tion are typ ically those p atients w ho have exp erienced Mu ltip le recip ient and d onor characteristics that
recu rrent ep isod es of rejection d u ring the first year follow - ad versely influ ence the occu rrence of acu te allograft rejec-
ing heart transp lantation (62). tion have been rep orted (Table 51.2) (60,63,64). The m ost
significant risk factor for the d evelop m ent of hyp eracu te
or early acu te allograft rejection is the p resence of p re-
100 CTRD: JAN, 1990–JUNE 1993: n = 1,251 form ed recip ient anti-hu m an leu kocyte antigen (H LA)
90 antibod ies d irected against the d onor allograft. A p anel-
Months Free from
reactive antibod y (PRA) valu e 10% su ggests significant
Free from first rejection (%)
first rejection (%)

80
1 61 sensitization in card iac allograft recip ients and is a signifi-
70 6
12
38
34
cant risk factor for the d evelop m ent of acu te allograft
60 24 31 rejection d u ring the early p ost-transp lant p eriod . H igh
36 29
50 reactivity is also a risk for early d eath from acu te or
chronic rejection, p articu larly if d irected against class I
40
H LA antigens (p ositive T-cell crossm atch) (65–69). A
30 recent registry analysis d em onstrated ad verse effects on
20 su rvival w ith PRA valu e 25% (70). This find ing also
10
ap p lies to heart transp lant recip ients w ho have d evelop ed
anti-H LA class II antibod ies against the d onor organ,
0 althou gh the d egree of risk is less clearly d efined (65,71). A
0 6 12 18 24 30 36 42
consensu s p anel w as convened in 2008 to ad d ress issu es of
Months after transplantation
sensitization in p atients aw aiting heart transp lantation
FIGURE 51.6. Actuarial and parametric freedom from initial rejection fol- (72). Gu id elines regard ing the frequ ency for antibod y
lowing heart transplantation. (Reprinted from Kubo SH, Naftel DC, Mills RM J r,
screening, testing m ethod ology, d esensitization, and p ost-
et al. Risks factors for late recurrent rejection after heart transplantation: a
multiinstitutional, multivariable analysis. Cardiac Transplant Research Data- transp lant m anagem ent w ere established . Recently, the
base Group. J Heart Lung Transplant 1995;14(3):410 (Fig. 1).) u se of virtu al crossm atching has been show n to be a u sefu l
The inflam m atory resp onse w ithin the allograft d u ring

acu te cellu lar rejection is p rom oted by a nu m ber of p roin-
flam m atory m olecu les, su ch as interleu kin-2, that correlate
w ith ep isod es of rejection (76–79). In ad d ition to cytokines,
increased expression of a nu m ber of ad hesion m olecu les
that correlate w ith the d evelop m ent of rejection (intercellu -
lar ad hesion m olecu le 1 and E-selectin) or the response to
therap y (vascu lar ad hesion m olecu le 1) has been reported
(76,80–86). The ind u ction of chem okine-gene and protein
exp ression w ithin the allograft, d etected w ith serial
end om yocard ial biop sies, also coincid es w ith leu kocyte
graft infiltration (87–90). These chem okines inclu d e the
T-cell chemoattractants ind ucible protein (IP)-10, monokine
ind u ced by IFN -(gam m a) (Mig), interferon ind u cible-T cell
FIGURE 51.7. Endomyocardial biopsy representative of Grade 1 R rejection alp ha chem oattractant (I-TAC), regu lated on activation
(previously Grade 2) showing mononuclear infiltrate extending from perivas- norm al T-cell exp ressed and secreted (RAN TES), and their
cular position to adjacent myocardium causing damage to myocytes and dis-
tortion of architecture. (Reprinted from Stewart S, Winters GL, Fishbein MC, recep tors CXCR3 and CCR5.
et al. Revision of the 1990 working formulation for the standardization of Antibody-mediated rejection is an increasingly recog-
nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant nized cause of morbid ity and mortality follow ing heart
2005;24(11): 1713 (Fig. 8).) transplantation. It can occur w ith or w ithout accom panying
cellular rejection, w ith a reported incid ence of 15% to 23%
(69,76,91,92). With the increasing use of mechanical circula-
ad ju nct in sensitized p atients aw aiting transp lant (73). For
tory support as a brid ge to transplantation, a greater per-
p atients w ith significant elevations in PRA, d esensitiza-
centage of patients are allosensitized preoperatively, placing
tion therap y w ith m od alities su ch as IVIg, ritu xim ab, and
them at increased risk for both antibod y-med iated and cellu-
p lasm ap heresis shou ld be consid ered (72).
lar rejection. Antibody-mediated rejection has been shown
Acute allograft rejection is a cellu lar process character-
to increase the risk of coronary artery vasculopathy and
ized by a m ononuclear inflam m atory response com posed
have an ad verse impact on survival. H umoral rejection can
pred om inantly of a lym p hocytic cell type that is d irected
be the result not just of presensitization to HLAs, but also of
against the d onor allograft (Fig. 51.7) (74). The rejection
primary antibody formation to HLA antigens post-trans-
phenom enon is a d iffuse p rocess and typ ically involves
plant (91). Presentation is most commonly within the first
both the left and right ventricles, perm itting d iagnosis of
month follow ing transplant, but may occur as early as sev-
rejection by rep resentative end om yocard ial biop sies of the
eral days follow ing transplant, or as late as 6 months or
right ventricu lar septum . Criteria w ere established in 1990
greater (92,93). When compared w ith cell-med iated allograft
for the histological analysis of m yocard ial biopsies in ord er
rejection, hu m oral-m ed iated allograft rejection typ ically
to grad e rejection (75). A revision of these original criteria
occu rs earlier follow in g h eart transp lantation, is m ore
w as p u blished in 2004, w hich serves as the current classifi-
highly associated w ith hem od ynam ic abnorm alities or
cation system for grad ing card iac allograft rejection (Table
u nexp lained left ventricu lar d ysfu nction, is m ore resistant
51.3) (74).
to au gm ented im m u nosu p p ression, is associated w ith a
higher frequ ency of allograft loss and m ortality, and is
m ore often associated w ith the d evelop m ent of coronary
allograft vascu lop athy (69). Risk factors for the d evelop -
m ent of hu m oral-m ed iated allograft rejection inclu d e
Table 5 1 .3 ISH LT st a n d a rd ized ca r d ia c biop sy recip ient fem ale gend er, p atients w ith a history of retrans-
gr a d in g: a cu t e cellu la r r eject ion p lan tation , elevated recip ien t PRA screen , recip ien t
Grade 0R No Rejection cytom egaloviru s (CMV) serop ositivity, p ositive p eriop er-
ative T-cell flow cytom etry crossm atch, and p ossibly those
Grade 1 R, mild Interstitial and/or perivascular infiltrate with up
to 1 focus of myocyte damage w ith p rior sensitization to OKT3 (69).
The m ain histologic featu res of hu m oral rejection
Grade 2 R, moderate Two or more foci of infiltrate with associated
inclu d e intravascu lar polym orphonu clear leukocytes and
myocyte damage
m acrop hages w ith or w ithou t associated end othelial
Grade 3 R, severe Diffuse infiltrate with multifocal myocyte sw elling; vascu locentric, lym p hocyte-p oor inflam m atory
damage / edema, / hemorrhage, infiltrate; and m yocyte inju ry, inclu d ing m yocyte necrosis
/ vasculitis
in areas ad jacent to affected vessels w ith infiltrates (76).
Adapted from Stewart S, Winters GL, Fishbein MC, et al. Revision of the 1990
Further evaluation of end om yocard ial biopsies from the
Working Formulation for the Standardization of Nomenclature in the Diagnosis of allograft w ith imm u nohistochem ical techniqu es id entify
Heart Rejection. J Heart Lung Transplant 2005;24:1710–20 (Table 1, page 1711) . d ep osition near cap illaries, arterioles, and sm all arteries of
FIGURE 51.8. Representative gross

anatomical and histological analysis of
humoral-mediated cardiac allograft rejection.
A:Cross section of a heart from a patient who
died of humoral rejection. There is diffuse
myocardial hemorrhage within both the
left and right ventricular walls. B and C:
Microscopic sections show intravascular
macrophages and neutrophils. There is con-
gestion of capillaries with focal interstitial
hemorrhage (original magnification, 33).
D–F: Immunofluorescence studies show
capillary positivity (green fluorescence) for
IgM (D), C1q (E), and HLA–DR (F). Yellow
fluorescence represents lipofuscin gran-
ules in myocytes (original magnification,
120). (Reprinted from Michaels PJ , Espejo
ML, Kobashigawa J , et al. Humoral rejec-
tion in cardiac transplantation: risk factors,
hemodynamic consequences and relation-
ship to transplant coronary artery disease.
J Heart Lung Transplant 2003;22(1):61 (Fig. 1).)
B C
D E F
p athological m arkers of hu m oral rejection that inclu d e Right ventricu lar end om yocard ial biop sy rem ains the
IgG, IgM, IgA, C1q, C3d , C4d , fibrinogen, and fibrin. The gold stand ard m ethod to assess allograft rejection in heart
p resence of sw ollen m acrop hages w ithin cap illaries can be transp lant recip ients. End om yocard ial biop sies are ini-
d istingu ished by staining w ith CD68/ KP1 (m onocytes/ tially p erform ed w eekly in ad u lts for the first m onth and
macrophages) and CD34 (end othelium) antibod y (Fig. 51.8) then every 2 to 4 w eeks over the next 2 m onths (94).
(69,76). The histological featu res of hu m oral-m ed iated The frequ ency of end om yocard ial biop sies are generally
allograft rejection are not necessarily u nique, and sp ecific d ecreased to every 3 to 4 m onths for the rem aind er of the
care m u st be taken in the interpretation of the m icroscopy first year and less frequ ently d u ring the second year in
and im m u nohistochem ical find ings (76). The d iagnosis of recip ients w ho d em onstrate no ep isod es of allograft rejec-
hu m oral-m ed iated rejection is further su pported by the tion (95). End om yocard ial biop sies are ind icated for sig-
find ing of d onor-sp ecific anti-H LA antibod ies in the seru m nificant changes in clin ical statu s su ch as u nexp lain ed
of the recip ient. tachycard ia, arrhythm ia, hyp otension, fever, abnorm al
hem od ynamics, or new echocard iographic abnorm alities. Table 5 1 .4 St ra t egies for t r ea t m en t of r ecu r r en t
Lim itations in the ability of end om yocard ial biopsy to or p er sist en t r eject ion w it h ou t
d etect allograft rejection are present d u e to significant sam - h em odyn a m ic com p rom ise
pling error as a result of sm all fragm ent or biopsy size, the
heterogeneou s natu re of acu te cellular rejection, and inter- Initial Treatment with Intravenous Methylprednisolone Plus
observer variability and skill (96,97). A failu re rate as high Cytolytic Therapy (OKT3 or ATGAM)
as 14% has been reported in the ability to d etect m od er- Consider one or more of the following:
ate–severe rejection w hen at least three fragm ents show Convert from azathioprine to mycophenolate or cyclophosphamide
(if evidence of humoral rejection)
mild rejection (96). Biopsies obtained w ithin the first 4 to
Convert from cyclosporine to tacrolimus
6 w eeks follow ing transplantation frequently d em onstrate
Raise maintenance prednisone to 0.2 mg/kg/d
changes consistent w ith ischem ic m yocard ial necrosis. Initiate photophoresis
Other lim itations of end om yocard ial biop sy inclu d e the Add methotrexate (rarely needed)
need for an invasive proced ure and the potential for inju ry Total lymphoid radiation (only as last resort because of potential for
to the tricu sp id valve w ith the d evelop m ent of tricu sp id late megakaryocytic leukemia)
insu fficiency.
Gene expression profiling has in recent years been Adapted from Bourge RC, Rodriguez ER, Tan CD. Cardiac allograft rejection. In: Kirklin
explored as a potential method for noninvasive immune sur- JK, Young JB, McGiffin DC, eds. Heart transplantation: Medicine, surgery, immunology,
and research. New York, NY: Churchill Livingstone; 2002:511 (Table 14–16).
veillance (98,99). This concept was valid ated in the Card iac
Allograft Rejection Gene Expression Observation (CARGO)
stud y (100). The Invasive Monitoring Attenuation Through gend er, d egree of H LA m ism atch, and p rior history of fre-
Gene Expression trial rand omized 602 patients w ho had qu ent allograft rejection are ad verse factors influ encing the
undergone transplantation 6 months prior to rejection sur- su ccess of corticosteroid w ithd raw al. Treatm ent of an acute
veillance using either gene expression profiling or endomy- episod e of cell-m ed iated allograft rejection is com plex,
ocard ial biopsy (101,102). A noninferiority comparison w as based on factors that inclu d e clinical featu res su ch as
performed between the two techniques w ith respect to a the p resence of abnorm al myocard ial fu nction, histologic
composite primary end point of rejection w ith hemod ynamic grad e or severity of the rejection ep isod e, and the tim e
compromise, graft d ysfunction d ue to other causes, d eath, or cou rse follow ing heart transp lantation d u ring w hich the
retransplantation. In this study, gene expression profiling, rejection ep isod e occu rs (Tables 51.4 and 51.5).
w hen compared w ith routine m yocard ial biopsy, w as not The infrequent occurrence of humoral rejection and the
associated w ith an increased incid ence of ad verse outcomes difficulty in diagnosis have made it difficult to evaluate the
and did result in the use of fewer endomyocardial biopsies. most effective form of treatment. Anecdotal reports have doc-
Another emerging technique of noninvasive immune moni- umented resolution with pulsed high-dose corticosteroids,
toring involves the measurement of T-cell function. The cytolytic therapy with OKT-3 or ATG, cyclophosphamide,
ImmuKnow test (Cylex, Columbia, MD) measures adeno- IVIg, and plasmapheresis (106). Cyclophosphamide is effec-
sine triphosphate release from activated T lymphocytes, tive in inhibiting B-cell activity, and it may reduce recipient
provid ing a w ay of assessing T-cell function and immune antibody prod uction and improve outcome. Intermittent
responsiveness. The assay has received FDA approval for therapeutic plasmapheresis is particularly important in
the assessment of cell-mediated immunity. The role of this removing circulating antibod ies against HLA and end othe-
assay in heart transp lantation h as yet to be d efined . lial antigens. H ep arin ad m inistration has been p rop osed
Kobashigaw a et al. (103) recently published a series examin- as u sefu l by inhibiting vascu lar sm ooth m u scle cell p rolif-
ing its use in 296 heart transplant patients, demonstrating eration. H ep arin bind ing to the end otheliu m m ay inhibit
some pred ictive value for infectious risk, but inconclusive
results w ith regards to rejection risk. Further studies w ill be
necessary to more clearly d efine the role of these emerging Table 5 1 .5 Th er a p eu t ic st r a t egy for r eject ion
noninvasive mod alities in the managem ent of heart trans- w it h h em odyn a m ic com p rom ise
plant recipients. Always Consider This a Life-Threatening Event
The p rim ary m ethod of m anagem ent of allograft rejec- Methylprednisolone 1 g IVdaily for 3 days
tion is p revention w ith m aintenance im m u nosu p p ressive Prompt inotropic support
therap y. The m ost com m on m anagem ent strategy is trip le- Swan–Ganz catheter for hemodynamic monitoring
d ru g therap y based on a calcineu rin inhibitor (cyclosp orine Prompt plasmapheresis daily for 3 days
or tacrolim u s) accom p anied by an antip roliferative agent Cytolytic therapy with ATGAM or OKT3
(m ycop h en olate or less com m on ly azath iop rin e or Heparin therapy
cyclop hosp ham id e) and corticosteroid s. More recently, Continue maintenance immunosuppression
Schedule photophoresis
evid ence su ggests a d ecreased incid ence of card iac allo-
graft vascu lop athy and rejection ep isod es w ith the u se of Adapted from Bourge RC, Rodriguez ER, Tan CD. Cardiac allograft rejection. In: Kirklin
sirolim u s or everolim u s (104,105). Attem p ts to w ean cor- JK, Young JB, McGiffin DC, eds. Heart transplantation: Medicine, surgery, immunology,
ticosteroid therap y are m ad e after 3 to 6 m onths. Fem ale and research. New York, NY: Churchill Livingstone; 2002, 513 (Table 14–18).
Table 5 1 .6 Fa ct or s a ffect in g t h e The risk of infection and su sceptibility to d ifferent

im m u n osu p p r essive st a t e organism s follow s a tem p oral p attern (Fig. 51.9) (112). The
of t h e t ra n sp la n t r ecip ien t source of infection can be grou p ed into fou r m ajor cate-
gories as has been p reviou sly d escribed (112). These are
Immunosuppressive therapy: dose, duration, and temporal sequence d onor-d erived infection, recip ient-d erived infection, noso-
Underlying immune deficiency: autoimmune disease, functional immune comial infections, and com m u nity-acqu ired infections. The
deficits risk of first infection follow ing heart transp lantation is
Integrity of the mucocutaneous barrier: catheters, epithelial surfaces highest d u ring the first m onth as a resu lt of the intensity of
im mu nosu p p ression. In general, infections d u ring the first
Devitalized tissue, fluid collections
m onth follow ing transp lant are m ost com m only nosoco-
Neutropenia, lymphopenia m ial or technical in origin. Com m on p athogens includ e
Metabolic conditions m ethicillin-resistant Staphylococcus sp ecies, vancom ycin-
Uremia resistant Enterococcus, and som e Cand id al sp ecies. Infec-
tiou s com p lications occu rring 1 to 6 m onths follow ing
Malnutrition
transplant are usually the result of opportu nistic p athogens
Diabetes or reactivation of latent infection. Op p ortu nistic p athogens
Alcoholism with cirrhosis have inclu d ed Pneumocystis carinii, Listeria monocytogenes,
Infection with immunomodulating viruses Nocardia asteroides, Cryp tococcal infection, and invasive
Aspergillosis. Comm u nity-acqu ired infection accou nts for a
Cytomegalovirus
greater p ortion of infections after 6 m onths. Risk factors for
Epstein–Barr virus infection early follow ing heart transp lantation inclu d e
Hepatitis B and C viruses old er recip ient age, ventilator su p p ort at the tim e of trans-
Human immunodeficiency virus p lantation, ventricu lar assist d evice at the tim e of trans-
p lantation, the u se of OKT3 ind u ction therap y, and p ositive
Adapted from Fishman JA, Rubin RH. Infection in organ-transplant recipients. d onor CMV serology (114). The lu ng is consistently the
N Engl J Med 1998;338(24):1742 (Table 1). m ost comm on site of infection (28%), follow ed by blood -
stream (26%), gastrointestinal tract (17%), u rinary tract
allogeneic recognition of receptors on the endothelial surface (12%), skin (8%), and w ou nd (7%) (107).
and improve coronary flow. Photopheresis with ultraviolet A Infection w ith CMV is of particular concern in heart
light following treatment with 8-methoxypsoralen has been transplant recip ients and is responsible for significant m or-
effective in treating cellular rejection in highly sensitized bid ity and m ortality (107,112,115). CMV infection is associ-
transplant recipients and may also be useful in the treatment ated w ith increased rejection ep isod es and card iac
of humoral rejection. Humoral-mediated allograft rejection allograft vascu lop athy (112). The increased u se of oral val-
frequently recurs and overall allograft loss exceeds 20%. ganciclovir for p rop hylaxis has been an im p ortant factor
in d ecreasing the incid ence of CMV infection in the recent
era (116,117). The tw o critical step s in the p athogenesis of
■ Infection CMV infection inclu d e reactivation from latency and sys-
Infection rem ains a lead ing cau se of m ortality d u ring the tem ic d issem ination. The p eak incid ence of infection w ith
first year follow ing heart transplantation (Fig. 51.3) CMV occu rs betw een the first and second m onth follow -
(107–112). The risk of infection is d epend ent on the cu m u la- ing heart transp lantation; how ever, the d u ration of tim e
tive risk of m u ltip le factors that alter the net state of to onset of CMV d isease has been stead ily increasing
im m unosupp ression of the patient and intensity of expo- (118). Risk factors for the d evelop m ent of CMV infection
sure to the p otential pathogen (Table 51.6) (111,112). In inclu d e the serologic statu s of the d onor and recip ient
recent years, ow ing to changing im m unosuppression w ith a seronegative recip ient and serop ositive d onor
strategies, the u se of antiviral and antibacterial p rop hy- m anifesting the greatest risk (Fig. 51.10). The u se of
laxis, and the em ergence of im proved antim icrobial thera- ind u ction therap y or treatm ent of rejection ep isod es w ith
pies, the p atterns of infection seen follow ing solid -organ OKT-3 or antilym p hocyte globu lin significantly increases
transp lantation have changed (109,112,113). Strategies for the risk of sym p tom atic CMV d isease and activation from
prophylaxis and ad vances in im m unosuppression p roto- latency (119).
cols have resulted in a d ecreased incid ence of infections The effects of acu te CMV infection in heart transp lant
from Pneumocystis carnii, CMV, and invasive fu ngal d isease recip ients u su ally inclu d e fever w ith constitu tional sym p -
(112,113). There also has been em ergence of antim icrobial- tom s and laboratory abnorm alities, inclu d ing leu kop enia,
resistant p athogens and the id entification of new infectiou s throm bocytop enia, atyp ical lym p hocytosis, and elevations
d isease synd rom es associated w ith transplantation and of liver transam inases. The sites of involvem ent of CMV
chronic im m u nosu pp ression. Gram -positive bacterial infection m ost com m only inclu d e the blood stream (43% of
infections continu e to be an im portant cau se of post-trans- infections), lu ngs (CMV p neu m onitis; 30% of CMV infec-
plant infections in recent eras (112). tions), and gastrointestinal tract (8% of infections). Other
Donor-derived Nosocomial, technical Activation of latent infection

Community-acquired
infection (donor or recipient) (relapsed, residual, opportunistic)
Dynamic assessment of risk of infection

Transplantation
Common infections in solid-organ transplant recipients
Recipient-derived <1 month 1–6 months >6 months

infection Infection with antimicrobial- With PCP and antiviral (CMV, HBV) Community-acquired pneumonia,
resistant species: prophylaxis: urinary tract infection
MRSA Polyomavirus BK infection, nephropathy Infection with Aspergillus, atypical
VRE C, difficile colitis molds, Mucor species
Candida species (non-albicans) HCV infection Infection with Nocadia Rhodo-
Aspiration Adenovirus infection, influenza coccus species
Catheter infection Cryptococcus neoformans infection Late viral infections:
Wound infection Mycobacterium tuberculosis infection CMV infectioon (colitis and
Anastomotic leaks and ischemia Anastomotic complications retinitis)
Clostridium difficile colitis Hepatitis (HBV, HCV)
Without prophylaxis: HSv encephalitis
Donor-derived infection Pneumocystis Community-acquired (SARS,
(uncommon): Infection with herpesviruses (HSV, West Nile virus infection)
HSV, LCMV, rhabdovirus VZV, CMV, EBV) Jc polyomavirus infection (PML)
(rabies), West Nile virus, HBV infection Skin cancr, lymphoma (PTLD)
HIV, Trypanosoma cruzi Infection with listeria nocardia, toxo-
plasma, strongyloides, leishmania,
Recipient-derived infection T. cruzi
(colonization):
Aspergillus, pseudomonas
FIGURE 51.9. Changing time course of infections following organ transplantation. HSV, herpes simplex virus; CMV,
cytomegalovirus; EBV, Epstein–Barr virus; HCV, hepatitis C virus; VZV, varicella zoster virus; RSV, respiratory syncytial virus; PTLD,
post- transplantation lymphoproliferative disease; MRSA, methicillin-resistant Staphylococcus aureus; VRE, vancomycin-resistant
Enterococcus faecalis; HIV, human immunodeficiency virus; PCP, Pneumocystis carinii pneumonia; HBV, hepatitis B virus; PML, pro-
gressive multifocal leukoencephalopathy. (Reprinted from Fishman J A. Infection in solid-organ transplant recipients. N Engl J Med
2007;357(25):2606 (Fig. 4).)
100
Negative–negative
Negative–positive
80 Positive–positive
Positive–negative
60
Freedom (%)
40
Donor to recipient
20 CMV status
0
0 6 12 18 24 30
Months after transplantation
FIGURE 51.10. Actuarial freedom from initial CMV infection according to CMV serologic status of donor and recipient before
transplantation. Dashed lines indicate duration of follow-up. Error bars indicate standard error. (Reprinted from Kirklin J K, Naftel
DC, Levine TB, et al. Cytomegalovirus after heart transplantation. Risk factors for infection and death: a multiinstitutional study.
The Cardiac Transplant Research Database Group. J Heart Lung Transplant 1994;13(3):394–404.)
FIGURE 51.11. CMV infection. (Reprinted from Fishman J A. Infection in solid-organ transplant recipients. N Engl J Med 2007; 357(25):
2609 (Fig. 5).)
less com m on featu res of CMV infections m ay inclu d e consensu s on the op tim al prophylactic regim en; how ever,
hep atitis, m yocard itis, chorioretinitis, and central nervou s there are im p ortant gu id elines. The intensity of prophy-
system involvem ent. Long-term sequelae of CMV infection laxis m ust be proportional to the intensity of the im m uno-
includ e an association w ith card iac allograft vascu lop athy, su p p ression and to the risk of viral reactivation;
post-transplant lymphoproliferative disorder, and increased p rop hylaxis m u st be initiated before reactivation of the
risk of d eveloping opportunistic infections (Fig. 51.11). The viru s; and effective antiviral p rop hylaxis w ith negative
use of CMV prophylaxis has been shown to decrease the su rveillance stu d ies m u st be m aintained for at least 3
incidence of cardiac allograft vasculopathy and the inci- m onths to p revent relap ses after p rematu re term ination of
dence of acute rejection (120). p rop hylaxis. There are cu rrently significant d ata available
The d iagnosis of d isease d u e to CMV is accom p lished to establish that antiviral therap y w ith ganciclovir red u ces
by d em onstrating virem ia or tissue invasion. CMV anti- the incid ence of CMV d isease in CMV-p ositive recip ients
genem ia assay is com m only utilized for d etection of CMV (123). H ow ever, there is no consensu s on d osing regim ens
in p erip heral blood w hile qu antitative PCR or hybrid cap - for heart transp lant recip ients, and sp ecific agents u sed
tu re assay for CMV DN A p rovid es the m ost sensitive vary across centers.
technology available for d etection of CMV in virtu ally any Antiviral therap y is u tilized in a th erap eu tic m od e to
tissu e or flu id . Ad d itionally, d em onstration of viru s on treat established infection w ith the aim of therap y to
biopsy of infected tissu e is u tilized in som e cases. erad icate the active infection, lim it any lasting p athologic
Antiviral agents are u tilized in three m od es to treat the effect, and p revent recu rrence. The generally accep ted
sequelae of CMV infection and d isease: prophylaxis, treat- stand ard for treatm ent of CMV d isease is 2 to 3 w eeks of
ment of established infection, and preemp tive therap y for intravenou s ganciclovir (ad ju sted for renal fu nction). Prior
high-risk p atients (112,119). The prevention of CMV infec- to availability of ganciclovir, the m ortality associated w ith
tion and CMV d isease throu gh the u se of an op tim al regi- CMV p neu m onitis w as as high as 75%. More recently, w ith
men of prophylaxis is an imp ortant strategy for heart the availability of ganciclovir, the m ortality of CMV p neu -
transp lant recip ients. Prophylactic therapy has been show n m onitis is 15%. The d u ration of therap y has not been
to d ecrease the risk of invasive infection in solid -organ clearly established , bu t trad itionally 2 to 3 w eeks is recom -
transp lant p atients (112,121,122). There is currently no clear m end ed . Many clinicians feel that tissu e-invasive d isease
shou ld be treated for longer p eriod s of tim e (u p to 6 The sequ elae of transm ission of hep atitis C viru s
w eeks). With the cu rren t availability of qu antitative (H CV) infection from d onor to the recip ient has been d if-
m easu res of CMV viral load , it m ay be ad visable to con- ficu lt to assess d u e to the lim ited d ata available. Lake et al.
tinu e treatm ent u ntil at least one viral load m easu re is (126) have rep orted on the long-term ou tcom e of H CV-
zero, w ith all sym p tom s h aving resolved . In p atients p ositive recip ients and fou nd no d ifference in su rvival
w ith severe d isease, p articu larly CMV p neu m onitis, com p ared w ith UN OS control grou p . There w as a 50%
CMV h yp erim m u ne globu lin m ay be u sed in com bina- incid ence of liver d ysfu nction and greater p rop ortion of
tion w ith ganciclovir, althou gh this com bination has not d eaths d u e to liver d isease in the H CV-p ositive recip ients.
been clearly su bstantiated ou tsid e of bone m arrow trans- Ong et al. (127) review ed the ou tcom es of H CV antibod y-
p lan t recip ients. The CMV in fection relap se rate can be as negative card iac recipients receiving H CV antibod y-positive
high as 20% in serop ositive in d ivid u als and even h igh er d on or h earts. Tw enty-th ree of 28 p atients d evelop ed
am ong p atien ts w ith p rim ary infection. d etectable virem ia, of w h om seven d evelop ed H CV-
The ad m inistration of antiviral therap y can be u tilized related liver d isease. Fou r of the seven p atients d evelop ed
in a preem ptive m od e in a select population of patients at severe cholestatic hep atitis, w hich contribu ted to a signif-
very high risk of d evelop ing clinical infection and d isease. icantly p oorer su rvival com p ared w ith those p atients
This p op u lation of p atients is generally d efined as having receiving hearts from H CV antibod y-negative d onors
received cytolytic therap y for ind u ction or treatm ent of (127). Based on the lim ited d ata available, it is reasonable
rejection, or having a high likelihood of d eveloping clinical to avoid the transp lantation of H CV-p ositive d onor hearts
infection by d em onstrating laboratory evid ence of CMV into H CV-negative recip ients.
infection by CMV antigenem ia or quantitative PCR testing, Transm ission of p rotozoal infection w ith Toxoplasma
bu t lacking clinically ap parent d isease. Antiviral therap y is gondii is an im portant consid eration for heart transp lant
then initiated on the basis of virem ia. recip ients. Pneu monitis, m yocard itis, and encephalitis are
Transm ission of infection from the d onor to recip ient the com m onest clinical synd rom es that u su ally first p res-
rem ains a significant concern follow ing heart transp lan- ent w ith u nd ifferentiated fever. In heart transplant recipi-
tation. This risk is m inim ized by rou tine screening of the ents, the risk of toxop lasm osis d u e to reactivation of the
d on or for a n u m ber of infectiou s agen ts (Table 51.7). Th e latent infection is low (128). The highest risk of d evelop ing
consequ ences of seroconversion from hep atitis B viru s d isease is in the setting of p rim ary infection (seronegative
(H BV) in recip ients su ggest that in fection resu lts in sig- recip ient w ho acqu ires the p arasite from a serop ositive
nificant long-term sequ elae. In h eart tran sp lant recip ien ts d onor) via infectiou s transm ission from the card iac allo-
w h o acqu ired H BsAg p ositivity after transp lan tation , graft (129). In a stu d y by Montoya et al. (118), a higher inci-
56% of p atients d evelop ed severe fibrosis and cirrh osis d ence of p reviou s T. gondii infection w as observed am ong
w ithin a m ean of 7.4 years after infection . Eighteen p er- recip ients (16%) com p ared w ith that of d onors (6%),
cent of d eaths in H BsAg-p ositive p atients w ere d u e to reflecting the increasing serop revalence of the infection
H BV-related liver failu re w ith th e ad verse effect of H BV w ith increasing age (118). Only 5.6% of p atients w ere
infection on su rvival ap p arent beyond 10 years (124). The d on or serop ositive/ recip ient seronegative. Of th e 32
u se of organs from d onors w ho are IgG H BcAb p ositive, d onor-p ositive/ recip ient-negative p atients for serology
IgM H BcAb negative, and H BsAg negative h as been testing, 16 w ere receiving trim ethop rim -su lfam ethoxazole
rep orted and su ggests a low risk of H BV transm ission and / or p yrim etham ine p rop hylaxis, and none of those
(125). Th e u se of organs from d on ors w ho are H BsAb 16 p atients d evelop ed toxop lasm osis. H ow ever, 4 (25%)
p ositive p robably carries a very significan t risk of H BV of the 16 d onor-p ositive/ recip ient-negative p atients w ho
transm ission. w ere not taking either trimethop rim -su lfam ethoxazole or
p yrim etham ine d evelop ed toxop lasm osis, and all d ied of
the infection. N one of the 98 p atients w ho w ere seroposi-
tive for T. gondii p reop eratively d evelop ed clinical evid ence
Table 5 1 .7 Rou t in e serology scr een in g of t h e
of reactivation of the infection. Whether a single tablet
d on or or ga n
(d ou ble strength) taken tw ice d aily, three tim es each w eek,
HIVantibody is sufficient to p revent toxoplasm osis in the d onor-positive/
HTLV-1 antibody recip ient-n egative grou p is u n clear at th is tim e an d it
Hepatitis B virus surface antigen (HBsAg) seem s p ru d ent that for those p atients a 6-w eek cou rse of
Hepatitis B virus surface antibody (anti-HBs) p yrim etham ine be ad d ed (130).
Hepatitis B virus core antibody (anti-HBc)
Hepatitis C virus (HCV) antibody
Cytomegalovirus (CMV)
Treponemal antigen (syphilis)
■ COMPLICATIONS AFTER THE FIRST YEAR
Toxoplasma antibody ■ Transplant coronary artery disease
Epstein–Barr antibody
West Nile virus Card iac allograft vascu lop ath y is a m ajor cau se of late
m orbid ity an d m ortality follow ing heart tran sp lantation.
Registry d ata from the International Society of H eart and

Lu ng Transp lantation ind icate the p resence of angiograph-
ically d etectable allograft vascu lop athy in 8% of patients
d u ring the first year, 32% by 5 years, and in 43% by 8 years
follow ing transp lant (2–4,131). Beyond 1 year, allograft
coronary artery d isease and post-transplant m alignancies
accou nt for the m ajority d eaths (Fig. 51.12) (2).
Card iac allograft vascu lopathy is an accelerated and
d iffused form of obliterative coronary arteriosclerosis,
resu lting in narrow ing and occlu sion of the coronary arter-
ies. It d iffers p athologically from typ ical coronary artery
atherosclerosis that is characterized by a m ore focal d istri-
bu tion (Fig. 51.13). End othelial d ysfu nction is an early fea-
tu re of card iac allograft vascu lop athy and p rogresses over
tim e. Im m u nologic and nonim m u nologic factors are
FIGURE 51.12. Hazard functions for specific causes of death after the first believed to resu lt in a rep etitive end othelial cell injury that
year following heart transplantation. (Reprinted from Kirklin J K, Naftel DC, elicits a su stained inflam m atory response w ithin the arte-
Bourge RC, et al. Evolving trends in risk profiles and causes of death after
heart transplantation: a ten-year multi-institutional study. J Thorac Cardio-
rial w all that is follow ed by intense intim al hyp erp lasia
vasc Surg 2003;125(4):883 (Fig. 2B).) in large and sm all caliber vessels, p roliferation of vascu lar
FIGURE 51.13. Morphological characteristics of cardiac

allograft vasculopathy. (Reprinted from Avery RK. Cardiac-
allograft vasculopathy. N Eng J Med 2003;349(9):830 (Fig. 1).)
Table 5 1 .8 Risk fa ct or s for t h e d evelop m en t of Table 5 1 .9 Recom m en d ed n om en cla t u r e for

ca r d ia c a llogra ft va scu lop a t hy ca rd ia c a llogr a ft va scu lop a t h y
Risk Factor ISHLT CAV0 (not significant): No detectable angiographic lesion
Diagnosis: coronary artery disease ISHLT CAV1 (mild): Angiographic left main (LM) 50%, or primary vessel
PRA screen value 20% with maximum lesion of 70% (including diffuse narrowing) without
Donor history of hypertension allograft dysfunction
Female donor
Hospitalized for rejection within 5 years of transplant ISHLT CAV2 (moderate): Angiographic LM 50%, a single primary vessel
70%, or isolated branch stenosis 70% in branches of two systems,
Adapted Taylor DO, Edwards LB, Mohacsi PJ, et al. The Registry of the without allograft dysfunction
International Society for Heart and Lung Transplantation: twentieth official adult ISHLT CAV3 (severe): Angiographic LM 50%, or two or more primary
heart transplant report—2003. J Heart Lung Transplant 2003;22(6):623 (Fig. 15). vessels 70% stenosis, or isolated branch stenosis 70% in all three
systems; or ISHLT CAV1 or CAV2 with allograft dysfunction (defined as
LVEF 45% usually in the presence of regional wall motion abnormali-
sm ooth mu scle cells, and m ononu clear cell infiltration. ties) or evidence of significant restrictive physiology
Concentric, circu m ferential, and longitu d inal intim al thick-
ening affect the epicard ial arteries w ith pruning of extra- Adapted from Mehra MR, Crespo-Leiro MG, Dipchand A, et al. International Soci-
ety for Heart and Lung Transplantation working formulation of a standardized
mu ral and intram yocard ial branches. Severe intim al
nomenclature for cardiac allograft vasculopathy—2010. J Heart Lung Transplant
thickening is associated w ith an increased rate of card iac 2010;29(7):719 (Table 2).
events su ch as sud d en d eath, m yocard ial infarction, allo-
graft d ysfu nction, and failu re (132).
Mu ltip le risk factors for the d evelop m ent of card iac d on or age, brain d eath, and viral in fection s, p articu larly
allograft vascu lopathy have been id entified , w hich su ggest CMV, are also thou gh t to be im p ortant in in flu encin g the
a com p licated interrelationship betw een possible im m u no- d evelop m ent of card iac allograft vascu lop ath y (131–135).
logic and nonim m u nologic m echanism s that com bine to Infection w ith CMV h as been associated w ith the d evel-
create an environm ent that facilitates end othelial inju ry op m ent of card iac allograft vascu lop athy, m ore severe
and p athological rem od eling (Table 51.8). The exact contri- an giograp hic d isease, an d a 5-year graft loss tw ice th at
bu tions from im m unologic and nonim m unologic m echa- of CMV-negative p atients (147). Recently, d ep letion of
nism s to the d evelopm ent of card iac allograft vascu lopathy vascu lar tissu e p lasm inogen-activator, occu rring w ithin
rem ain controversial (133–136). Data sup porting the role of 3 m onths follow ing tran sp lan tation , has been associated
early recu rrent rejection ep isod es in the d evelop m ent w ith an 8.3-fold in crease in risk of th e d evelop m en t of
of card iac allograft vascu lop athy have not consistently an giograp hically evid ent coronary d isease an d a greater
d em onstrated a clear association betw een rejection and car- likelihood of d eath or retran sp lan tation .
d iac allograft vasculopathy (136–138). Other d ata su ggest A con sen su s statem en t from th e ISH LT w orkin g
that the d evelop m ent of card iac allograft vascu lop athy is grou p on Classification of Card iac Allograft Vascu lop athy
associated w ith chronic allograft rejection throu gh d irect recently ou tlined a fram ew ork for the stand ard ization of
and ind irect p athw ays of allorecognition that resu lt in CD4 nom enclatu re for allograft vascu lar d isease in heart trans-
T-cell activation and expansion of T-cell clones w ith speci- p lant recip ients (Table 51.9) (148). Cu rrent consensu s rec-
ficity for mu ltip le H LA–DR allop eptid es, d espite treatm ent om m end ations inclu d e the u se of coronary angiograp hy
w ith im m u nosu p pressive d rugs (131,139–142). Activation cou p led w ith assessm ent of card iac allograft fu nction as
of T cells throu gh the ind irect p athw ay can elicit B-cell acti- the basis for cu rrent nom enclatu re. Intravascu lar u ltra-
vation w ith d e novo d evelop m ent of anti-H LA IgG anti- sou nd (IVUS), in com bination w ith conventional angiog-
bod ies to the allograft. The d evelopm ent of anti-H LA rap hy, has been show n to enhance sensitivity in early-stage
antibod ies, as w ell as antibod ies to antigens exp ressed by d isease an d to id entify con cen tric lu m in al n arrow ing
end othelial cells, has been show n to be pred ictive of the (Fig. 51.14) (149–151). IVUS h as h ad an increasin g role in
d evelop m ent of graft atherosclerosis (143–145). Anti-H LA recent years in the d iagnosis of CAV. Silent p rogression of
antibod y p rod u ction in the recip ient m ay thu s correlate CAV d etected by IVUS h as been show n to be an im p or-
w ith a high risk for transp lantation-related vascu lop athy tant p red ictor of long-term m orbid ity and m ortality
by both reflecting an activated ind irect T-cell recognition (150). Althou gh u sefu l as an ad ju nctive tool, cu rren t con-
pathw ay and an efficient alloantigen-presentation arm of sensu s recom m end ations d o not ad vocate the rou tine u se
the im m u ne resp onse. H ow ever, evid ence imp licating the of IVUS as a su rveillance m od ality (148). Dobu tam in e
d egree of m ajor histocom patibility com plex (MH C) m is- ech ocard iograp h y is also h elp fu l in id en tifying m yocar-
match w ith su bsequent d evelopm ent of card iac allograft d ial ischem ia in p atien ts w ith coronary allograft vascu -
vascu lop athy has not been uniformly observed (146). lop athy, bu t is lim ited by its sensitivity. Recent d ata have
N on im m u n ologic factors su ch as hyp erlip id em ia, d em onstrated a correlation betw een circu lating chem okine
hyp ertension , obesity, d iabetes, organ p reservation , allo- levels and d evelop m ent of coronary artery vascu lop athy
graft ischem ia/ rep erfu sion inju ry, su rgical trau m a, old er in hu m ans (152). ITAC/ CXCL11, a CXCR3 ligand , w as
FK506-bind ing p rotein 12 (FKBP12). The sirolim us–

FKBP12 d im eric m olecu le inhibits the m am m alian target of
rap am ycin and u p regu lates the cyclin-d ep end ent kinase
inhibitor p 27kip 1, lead ing to inhibition of cell cycle p ro-
gression at the G1 to S p hase (164,165). Use of sirolimu s in
d e novo kid ney allograft recip ients has been show n to be
effective in red u cing allograft rejection (166,167). Use of
sirolim u s in heart transp lantation recip ients is m ore lim -
ited . In a recent, rand om ized stu d y of 46 p atients by
A B Mancini et al. (104), sirolim u s ap p eared to slow the pro-
gression of established card iac allograft vasculopathy
FIGURE 51.14. IVUS for the evaluation of cardiac allograft vasculopathy.
Identical site in the left circumflex artery from a baseline (A) and 1-year (104). Other stu d ies have d em onstrated sim ilar find ings
follow-up (B) study. There is no intimal thickening at baseline. However, (168). Eisen et al. (105) recently rep orted on the resu lts of a
when the same site is identified using pericardium and a branch vessel as a large, m u lticenter, rand om ized trial com p aring everolim us
landmark, significant intimal thickening (0.6 mm) is identified at the same site. (at tw o d oses, 1.5 and 3.0 m g/ d ) and azathiop rine, each in
This is an example of de novo lesion of transplant vasculopathy. (Reprinted
from Kapadia SR, Nissen SE, Ziada KM, et al. Development of transplantation com bination w ith p red nisone and cyclosp orine, for the
vasculopathy and progression of donor transplant atherosclerosis: a com- p reven tion of vascu lop athy after heart tran sp lan tation
parison by serial intravascular ultrasound imaging. Circulation 1998; 98(24): (105). Statin lip id -low ering agents w ere ad m inistered to
2672–78.)
all p atien ts. Intravascu lar u ltrasonograp h y w as p er-
form ed at base line (w ith in th e first 6 w eeks after trans-
associated w ith coronary artery vascu lop athy becau se of p lan tation ) and at 12 m on ths. In th e grou p s receivin g
elevated seru m levels and im m u nohistochem ical localiza- everolim u s, significantly few er p atients reached the com -
tion. ITAC/ CXCL11 m ay have a cau sative role in the p osite p rim ary end p oin t of d eath , graft loss or retrans-
p athogenesis of this d isease and m ay p rovid e a w ay to p lan tation , loss to follow -u p , rejection of grad e 3A or
p rosp ectively id entify p atients at risk for the d evelop m ent higher, or rejection involving hem od yn am ic com p ro-
of coronary artery vascu lop athy. Becau se of lim itations in m ise. Rates of graft loss an d d eath d id n ot d iffer signifi-
sp ecificity and lack of stand ard ization in m easu rem ents, cantly am ong the stu d y grou p s, bu t the grou p receiving
the consensu s p anel has not inclu d ed end om yocard ial azath iop rin e h ad a higher incid en ce of rejection of at least
biop sy find ings, biom arkers, card iac trop onins, C-reactive grad e 3A than d id the everolimus grou ps. The results of
p rotein levels, m icrovascu lar fu nction testing, and stress- intravascu lar u ltrasonography show ed that the change in
based im aging in the cu rrent gu id elines for nom enclatu re intim al variables, inclu d ing the increase in the m axim al inti-
(148). mal thickness, w as significantly sm aller in both everolim u s
Therapy for treatment of allograft vasculopathy has been grou p s. The incid ence of vascu lop athy w as low er in the
disappointing, and strategies are usually d irected tow ard its everolim u s grou p s, p articu larly the higher-d ose grou p .
prevention. The use of calcium antagonists, ACE inhibitors, This is the first stu d y to d em onstrate the effect of a p artic-
hydroxymethylglutaryl Co-A reductase inhibitors, antioxi- u lar im m u nosu p p ressive regim en on the d evelop m ent of
dants, and intensified immunosuppression provid es mod est allograft vascu lop ath y. If th ese d ifferen ces p ersist in su b-
benefit and has been suggested to limit disease progression sequ ent years, this effect of everolim u s cou ld translate
and improve outcome (153–157). Because of the diffuse into a su bstantial long-term benefit for p atients w ho
nature of cardiac allograft vasculopathy, percutaneous and received th e d ru g.
surgical revascularization proced ures have a limited role.
Transmyocard ial revascularization has been performed , but
there has been little reported long-term success. Retrans-
■ Malignancies
plantation for significant coronary allograft vasculopathy is H eart transp lant recip ients have a m arked ly increased
the only method of treatment. Post-transplant outcomes fol- risk of d evelop ing a m alignant d isord er follow ing heart
lowing retransplantation for cardiac allograft vasculopathy transp lantation, p articu larly lym p hop roliferative d isor-
approach that of primary transplantation. d ers, cu taneou s m alignancies, and carcinom a of the lu ng
Cellu lar p roliferation has been id entified as a central (109,169). Malignancies are a m ajor cau se of late m ortality
process to the p athogenesis of allograft vascu lop athy. follow ing heart transp lantation (Fig. 51.12). Lym p hom as
Sirolim u s and everolim u s, d rugs of a new class of m acro- occu r in ap p roxim ately 6% of heart transp lant recip ients
cyclic im m unosup pressive agents w ith u nique antiprolifer- and constitu te 22% of all m alignancies com p ared to 5% of
ative activity, have recently been show n to red u ce the the general p op u lation (170,171). Cancers of the p rostate,
incid ence and progression of card iac allograft vasculopa- colon and rectu m , fem ale breast, and u terine cervix occu r
thy (158–163). Unlike calcineu rin inhibitors, sirolim us d oes at a sim ilar prevalence com pared to the general p opu lation.
not inhibit interleukin prod u ction from antigen-ind uced T- The com bination of im m u nosu p p ression and a history of
cell activation, bu t rather inhibits cellu lar proliferation and p rior sm oking accou nt for an increased risk of d evelop -
migration in resp onse to alloantigens. Sirolim us bind s to ing lu n g can cer in heart tran sp lan t recip ien ts (172). N o
relationship has been d em onstrated betw een the typ e of has been sh ow n to slow th e p rogression of certain p ost-
m aintenance im m u nosu p p ression and the risk of m alig- transp lant m alignancies (178).
nancy (173). The m ost im p ortant factors associated w ith In ad d ition to lym p hop roliferative d isord ers, there is a
the d evelop m ent of neop lasm s follow ing heart transp lan- significantly increased risk of d evelop ing nonm elanom a
tation are alterations in im m u ne fu nction and oncogenic skin cancers follow ing heart transp lantation. Squam ous
viru ses [i.e., Ep stein–Barr viru s (EBV)]. cell carcinom a of the skin is m ore prevalent as com pared
Over 90% of p ost-transplant lym phom as are non- w ith basal cell carcinom a. This trend is op p osite of w hat is
H od gkin’s typ e and consist m ostly of abnorm al prolifera- observed in the general p op u lation (169). Therapy for treat-
tions of B lym p hocytes. These tum ors d isplay a variety of m ent of skin cancers after heart transp lantation follow s tra-
morphologies ranging from sim ple B-cell hyperplasia to d itional d erm atologic ap p roaches based on histology and
aggressive m onoclonal im m unoblastic varieties and are clinical stage of the d isease.
more correctly characterized as a post-transplant lym pho-
proliferative d isord er (PTLD). PTLD is m ore com m on in
heart and heart-lu ng recipients than in kid ney recipients, ■ OTHER MAJ OR COMPLICATIONS OCCURRING
and it is m ore com m on in p ed iatric patients com p ared w ith FOLLOWING HEART TRANSPLANTATION
ad ults (170). Extranod al involvement is seen in 70% of
cases; central nervous system and intra-abd ominal involve-
■ Chronic renal insufficiency
ment are p articu larly comm on (170,174). EBV is believed to Acu te and chronic renal insufficiency accounts for signifi-
have a relationship to PTLD through ind u ction of B-cell cant m orbid ity and rep resents a risk factor for m ortality
proliferation, and infection is acquired m ost com m only follow ing heart transp lantation. In earlier cohorts, 40% of
from a serop ositive d onor. EBV-seronegative recip ients are transplant recipients suffered from severe renal d ysfu nc-
at greater risk of acquiring PTLD (24 to 33 tim es greater tion at 10 years. Recent d ata from the ISH LT registry, how -
than serop ositive recipient), bu t PTLD m ay also occu r d u r- ever, d em onstrates a d ecreased rate of renal d ysfunction in
ing EBV reactivation (169). Ind uction therapy or treatm ent m ore contem p orary cohorts, w ith a red u ction of app roxi-
of rejection ep isod es w ith cytolytic agents such as antilym - m ately 11% at 5 years (Fig. 51.15) (2). As m any as 4% to 8%
phocyte globu lin or OKT3 increases the risk of PTLD (175). of p atients w ill d evelop severe renal d ysfu nction, requ iring
Sw innen et al. (176) reported a m arked ly increased inci- rep lacem ent therap y w ithin 5 to 10 years (179–183). In a
d ence w hen the cum u lative OKT-3 d ose exceed ed 75 m g; significant nu m ber of p atients, there is a d ecrease in the
how ever, this observation has not been consistently glom eru lar filtration rate by 30% to 50% d u ring the first
d em onstrated . There is general consensu s that cytotoxic 6 m onths after transp lantation that is follow ed by stabiliza-
im m unosupp ressive d ru gs m ay p erm anently elim inate T- tion or a slow er rate of loss of renal fu nction (180). This
cell clones that are necessary for controlling m alignant cells d ecline is alm ost 10 tim es as great as exp ected in a healthy
or latent oncogenic viru ses. p op u lation (184). Su bsequ ent initiation of d ialysis has a
The clinical p resentation of PTLD is very heterogeneou s significantly ad verse influ ence on su rvival w ith only 60%
(169,177). Early d isease generally occu rs w ithin the first of p atients su rviving 1 year follow ing the start of d ialysis
12 m onths and is a frequ ently localized or nod al d isease. (181). Risk factors for early acu te renal failu re inclu d e recip-
Focal lym phad enopathy is a com m on initial presentation. ient d iabetes, ad vanced recip ient age, p retransplant creati-
Early PTLD is generally polyclonal by DN A analysis and nine, and p reexisting recip ient hyp ertension. Recipient
often regresses follow ing red u ction in im m u nosu p p res- creatinine and d iabetes rem ain strong risk factors for the
sion. In contrast, late PTLD often presents w ith d isseminated d evelop m ent of late chronic renal d ysfu nction ( 7 years
disease, d emonstrates monoclonal B-cell proliferation, fails p ost-transp lant) (3).
to respond to red uced immunosuppression, and carries a Calcineurin inhibitors (i.e., cyclosp orine and tacrolimus)
1-year mortality rate in excess of 75%. CNS involvement are significantly associated w ith both the acute functional
may occur in up to 27% of patients (169,177). Gastrointesti- nephrotoxicity and chronic structural nephrotoxicity that
nal tract and pulmonary involvement also occur. Aggressive occu rs follow ing heart transp lantation (185–187). Cal-
monoclonal B-cell types of PTLD may occur w ithin the first cineurin inhibitors contribute to acute nephrotoxicity by
year. cau sing constriction of the afferent renal arterioles that
The association betw een PTLD and viral infections resu lts in a d ecrease in glom eru lar filtration rate (187).
has p rom p ted the u se of antiviral p rop hylaxis d u ring the Cyclosp orine has also been show n to ind u ce an elevation
early p ost-transp lant p eriod and d u ring p eriod s of au g- of the end othelin-1 level (188), and to stim u late the ren-
m en ted im m u nosu p p ression. Red u ction in im m u n osu p - nin–angiotensin–ald osterone system (189). This acu te
p ression m ay be effective in ap p roxim ately 60% of cases nep hrotoxicity is d ose d ep end ent and reversible. Previ-
(169,177). Ad d ition al treatm en ts m ay inclu d e excision ou s rep orts h ave su ggested that early ren al inju ry resu lts
of the lesion if localized , localized rad iation therap y for in long-term p rogressive nep hrop athy. The chronic effects
d iscrete m asses or cen tral n ervou s system lesions, or of cyclosp orine nep h rotoxicity are ch aracterized by a
m od ified n on-H od gkin ’s ch em otherap y for w id esp read p rogressive afferent arteriolopathy and interstitial fibrosis
d isease. Th e u se of new er p roliferation signal inh ibitors (186,190,191). The chronic nephrotoxic effects of calcineurin
FIGURE 51.15. Kaplan–Meier 100
Freedom from severe renal dysfunction (%)

freedom from severe renal dysfunc-
tion, stratified by era, for transplants 90
performed from April 1994 to J une
2007. (Reprinted from Taylor DO, 80
Stehlik J, Edwards LB, et al. Registry
70
of the International Society for Heart
and Lung Transplantation: twenty-
60 * Severe renal dysfunction = creatinine > 2.5 mg/dl, dialysis or
sixth official adult heart transplant
report—2009. J Heart Lung Trans- renal transplant
50
plant 2009;28(10):1020 (Fig. 16).)
40
p < 0.0001
30
20
Freedom from severe renal dysfunction 2001–6/2007 (N = 10,751)
10
Freedom from severe renal dysfunction 4/1994–2000 (N = 11,181)
0
0 1 2 3 4 5 6 7 8 9 10
Years
inhibitors are thou ght to be irreversible and d ose ind e- factors, and other risk factors for chronic renal insu ffi-
pend ent (186,192). Risk factors for the d evelopm ent of ciency su ch as hyp ertension, d iabetes m ellitu s, and hyperc-
renal insu fficiency w ith calcineu rin inhibitors u se follow - holesterolem ia. This concep t is su p p orted by the find ing
ing heart transp lantation have not been clearly d efined but that althou gh there w as a strong association betw een p re-
may includ e recipient age at the tim e of heart transplanta- op erative seru m creatinine and d evelop m ent of chronic
tion and glom eru lar-filtration rate at 1 year follow ing heart renal insu fficiency in the stu d y by Vossler et al. (193), 19%
transp lantation. Vossler et al. (193) cond ucted a 5-year ret- of p atients w ith norm al p reop erative creatinine also exp eri-
rosp ective analysis of heart transp lant recip ients w ho su r- enced chronic renal insufficiency follow ing heart trans-
vived for 1 year follow ing operation. Patients w ere p lantation. Renal fu nctional reserve before transp lantation
d ivid ed into three grou ps based on perioperative renal is probably an im portant factor in d eterm ining w hether a
function: (1) preoperative creatinine concentration 1.5 mg/ p atient w ill tolerate long-term treatm ent w ith calcineurin
d L and a p ostop erative (first 4 d ays) creatinine 2.0 m g/ inhibitors. H istologic evid ence of p rogressive glom eru-
d L; (2) p reop erative creatinine of 1.5 m g/ d L but a p ost- losclerosis and loss of functioning glom eruli is present in
op erative creatinine of 2.0 m g/ d L; (3) preoperative crea- p atients treated w ith calcineu rin inhibitors d esp ite m ain-
tinine of 1.5 m g/ d L. N early 30% of patients experienced taining a stable seru m creatinine (194). Thu s, all patients
chronic renal insufficiency (serial serum creatinine 2.0 mg/ treated w ith calcineu rin inhibitors are likely to have som e
d L) on tw o or m ore m on th ly exam in ations. The m ean renal d am age, bu t that the d egree of fu nctional im pairm ent
preoperative seru m creatinine w as 1.6 m g/ d L in patients is highly d epend ent on the d egree of p retransplant renal
w ho exp erienced chronic renal insu fficiency, w hereas it d isease.
w as 1.3 mg/ d L in p atients w ho d id not (p 0.01). The frac- There is no effective treatm ent to reverse p rogressive
tion of p atients in w hom chronic renal insu fficiency d evel- renal d ysfu nction follow ing heart transp lantation. Alter-
oped w as highest in Group 3 (55.3%), low er in Grou p 2 ations in cyclosp orine d osing regim ens have been pro-
(25.5%), and low est in Grou p 1 (18.7%) (p 0.01). After p osed bu t have not been consistently d em onstrated to
ad justing for m u ltiple p otential confou nd ing variables, have a significant im p act (195). There are no consistent
includ ing cyclosp orine d osage, the risk of chronic renal d ata to su ggest that treatm ent w ith calciu m channel block-
insu fficiency linearly d ecreased in the three grou p s, strat- ers, statins, or ACE inhibitors has a significant benefit on
ified by p eriop erative renal fu nction (relative risk, 1.82; long-term renal fu nction (180,196). Calcineu rin-sp aring
95% confid ence interval, 1.23–2.7). Althou gh p retrans- im m u nosu p p ressive p rotocols have been p rop osed as one
p lant seru m creatinine w as the best p red ictor of the d evel- alternative to red u ce the risk of chronic renal insu fficiency
op m ent of chronic renal insu fficiency in the stu d y by second ary to calcineu rin inhibitors. Alternative strategies
Vossler et al. (193), the p athop hysiology of chronic renal involve red uction of d oses of calcineurin inhibitors w ith
insu fficiency ap p ears m ore com p lex and p robably resu lts introd u ction of non-nephrotoxic im m unosu ppressants su ch
from m u ltip le interacting factors. These factors inclu d e as m ycop henolate m ofetil and sirolim u s. This strategy is
the acu te and chronic nep hrotoxic effects of calcineu rin cu rrently being investigated extensively in renal transp lan-
inhibitors, the abnorm al renal fu nction in p atients w ith tation, and it has been show n to im p rove renal fu nction, at
ad vanced heart failu re, transp lant op eration w ith associ- least in the short term (197,198). More recently, som e bene-
ated card iop u lm onary byp ass, recip ient age, im m u nologic fit has been show n w ith calcineu rin-free p rotocols utilizing
sirolim u s in com bination w ith m ycop henolate m ofetil ■ METABOLIC AND ENDOCRINE DISORDERS
(199). The su bstitu tion of m ycophenolate m ofetil for aza-
thiop rine, w ith a concom itant red uction in the d ose of ■ Hyperlipidemia
calcineu rin inhibitors, has been reported to im p rove renal
The incid ence of hyp erlip id em ia follow ing heart transp lan-
fu nction, w ithou t increasing the rate of allograft rejection
tation has been rep orted to be as high as 60% to 80% of
(200,201). In ad d ition to changes in im m unosu p p ressive
heart transplant recip ients and is m anifest by elevated
therap y, continu ed long-term m anagem ent of nonim -
seru m levels of total cholesterol, low -d ensity lipoprotein
mu nologic factors, (i.e., hypertension and d iabetes m elli-
(LDL) cholesterol, ap olip op rotein B, and triglycerid e (211).
tu s) rem ain im p ortant.
The etiology of hyp erlip id em ia follow ing heart transp lan-
tation is attribu table to several factors that inclu d e d iets
■ Hypertension high in fat, fam ilial p red isp osition, and im m unosup pres-
sive therap y w ith corticosteroid s and calcineu rin inhibitors
The d evelopment of systemic hypertension is a significant
(212,213). Cyclosp orine blood levels have been show n
complication follow ing heart transplantation. The incid ence
to correlate d irectly w ith total p lasm a cholesterol, LDL
of hypertension has been reported to range from 40% to 90%
cholesterol, and ap oB and inversely w ith high-d ensity
in the era of calcineurin inhibitors (202). The overwhelming
lip op rotein (H DL) cholesterol and ap oA-I (the antiathero-
factor responsible for the d evelopment of hypertension fol-
genic p rotein com p onent of H DL). In ad d ition, significant
lowing heart transplantation is the use of calcineurin
correlation w ith the total cholesterol/ H DL ratio and
inhibitors. Add itional risk factors thought to be important
cyclosp orine levels have been rep orted (213). Tacrolim us
includ e male gend er, a family history of hypertension, and
ap p ears to have less ad verse effects on lip id m etabolism
recipient age 20 years (203). How ever, the additional influ-
w hen com p ared w ith cyclosp orine (207).
ence of these factors in the setting of calcineurin use may
The benefits of cholesterol red u ction in p atients w ith
be relatively m inor (203,204). Calcineurin inhibitors are
coronary artery d isease and in high-risk patients w ithout
thou ght to contribu te to the d evelop m ent of hyp ertension
established coronary artery d isease are w ell established .
by a d irect effect on sym pathetic stim ulation (205), neu ro-
All-cau se m ortality is significantly red u ced d ue to a d ra-
horm onal activation (189), and p eripheral vasoconstriction
matic red u ction in coronary end p oints. The benefit of
throu gh release of end othelin-1 (206). Corticosteroid s may
treatm ent of hyp erlip id em ia in heart transp lant recip ients
also contribu te to the d evelopm ent of hypertension sec-
has been d em onstrated by Kobashigaw a et al. (156) in a
ond ary to their m ineralocorticoid effect; how ever, heart
stu d y of 97 heart transp lant recip ients rand om ized to ther-
transp lant recipients on steroid -free immunosuppressive
ap y w ith or w ithou t p ravastatin. Pravastatin at d oses of 20
regim ens have a sim ilar d egree of p ostop erative hyp er-
to 40 m g d aily p rod u ced a 22% low ering of total plasm a
tension. Recently, several stu d ies have d em onstrated the
cholesterol. There w as no change in the nu m ber of episod es
d evelopment of less-severe hypertension w ith the use of
of rejection, bu t there w as a d ram atic red u ction in episod es
tacrolim us w hen compared w ith cyclosporine in heart trans-
of rejection associated w ith hem od ynam ic com prom ise,
plant recipients (207–209). Patients receiving tacrolimus-
as well as a marked improvement in survival. There was
based im m u nosu p p ression have been show n to have a
also a lower incidence of coronary vasculopathy, as deter-
low er incid ence of new onset hyp ertension and requ ire
mined by angiography or IVUS. The mechanism of this
few er antihypertensive agents for m anagement (207).
effect w as most likely related to cholesterol reduction. H ow -
The treatm ent of p ost-transp lant hyp ertension is sim ilar
ever, a significant decrease w as noted in the cytotoxicity of
to that of essential hypertension. Calcium channel–blocking
natural killer cells, suggesting that an immunologic mecha-
agents are u su ally the first line of therapy for hyp ertension
nism may contribute to the effectiveness of this intervention.
in patients treated w ith cyclosporine. Diltiazem has the
Despite the potential for rhabd omyolysis in patients receiv-
ad vantage of d ecreasing the cyclosporine d ose and there-
ing pravastatin together w ith cyclosporine, no elevation in
fore d ecreasing im m u n osu p p ression costs. Angiotensin-
creatine kinase, transaminases, myositis, or rhabdomyolysis
con vertin g en zym e (ACE) in h ibitors are also u sed for
w ere d ocumented over the 12 months of stud y.
treatm ent of hyp ertension in transp lant recip ients. A ran-
d om ized trial com p aring d iltiazem an d lisin op ril in th e
treatm ent of p ost-transp lant hyp ertension d em onstrated
■ Hyperglycemia
equal efficacy (210). Monotherapy is effective in 50% of The rep orted incid ence of d iabetes m ellitu s follow ing
patients. Therapy with both agents is generally required to transplantation has varied w id ely (from 2% to 46%), largely
obtain ad equate blood pressure regulation, and peripheral d u e variations in the criteria u sed to d efine d iabetes m elli-
alpha-adrenergic blocking agents such as doxazosin, periph- tu s after transp lantation. The onset of d iabetes m ellitus
eral arterial d ilators such as hydralazine and minoxid il, and after organ transp lantation is related to exogenou s glu co-
centrally acting sympathetic inhibitors such as clonid ine corticoid ad ministration. Glucocorticoid s impair hepatic
may be useful ad juvants to therapy w ith calcium channel and extrahepatic actions of insulin, probably at the p ostre-
blockers and ACE inhibitors if first-line therapy is not suffi- ceptor level as neither bind ing of insulin to its receptor nor
cient in controlling blood pressure. the number of insulin receptors is affected by glucocorticoid
ad m inistration. Glu cocorticoid s stim u late hepatic synthe- directly related to dose and duration of corticosteroid expo-
sis of glu cose from am ino acid s and glycerol, stim ulate the sure. However, the process of bone loss in heart transplant
d eposition of glu cose in the liver as glycogen, d im inish recipients is believed to be multifactorial and includes the
glu cose u tilization, increase protein breakd ow n, and acti- effects of corticosteroid s in addition to the adverse effects of
vate lip olysis. The net effect of these physiologic alterations cyclosporine on bone remodeling and the high prevalence of
is to increase blood glu cose levels. post-transplant renal insufficiency (215,221,222).
Calcineurin inhibitors, cyclosporine and tacrolimu s, also Early therap eu tic m easu res to red u ce the d egree of bone
ind u ce glucose intolerance. Cyclosporine accu m ulates in loss follow ing heart transp lantation is essential. Therapy
pancreatic islet cells cau sing d ecreased B-cell volu me, focu ses on (a) su p p lem entation of elem ental calciu m
d iminished insu lin secretion, and hyperglycemia (214). (15,000 m g/ d ), (b) ad m inistration of vitam in D prepara-
These effects are reversible w ith d iscontinuation of the tions (i.e., calcitriol), (c) u se of bisp hosp honates to inhibit
d rug. In ad d ition, cyclosporine may potentiate the d iabeto- bone resorp tion, and (d ) institu tion of a p hysical exercise
genic effects of glucocorticoid s by d ecreasing their clear- training p rogram. In selected p atients, m easu rem ent of
ance, as both d ru gs are metabolized by the cytochrome P450 gonad al horm ones w ith appropriate replacement therapy
system. Tacrolimus has been show n to have a d irect toxic and u tilization of calcitonin for p atients that d o not tolerate
effect on p ancreatic islet cells sim ilar to that of cyclosp orine. bisp hosp honates m ay be ind icated . Patients in w hom
H ow ever, w ith more conservative d osing, this agent can be osteop orosis is d iagnosed by p retransp lant bone m ineral
effectively used w ithout an excessive risk of d iabetes. d ensity m easu rem ents shou ld be treated w ith antiresorp -
tive therap y p rior to transp lantation.
■ Osteoporosis
Osteoporosis is a disease characterized by low bone mass ■ ABDOMINAL AND GASTROINTESTINAL
that results in a significantly increased risk of fracture. Osteo- COMPLICATIONS
porosis is diagnosed by bone mineral d ensity criteria devel-
Minor and m ajor life-threatening gastrointestinal com pli-
oped by the World Health Organization that is generally
cations occu r at a relatively high frequ ency follow ing heart
obtained from evaluation with dual-energy x-ray absorp-
transp lantation (Table 51.10). The rep orted incid ence of
tiometry. Heart transplant recipients are at particular risk for
gastrointestinal com p lications in several series has varied
developing osteoporosis due to a number of pre- and post-
from 9% to 34% (223–226). The large variability in the
transplants risk factors that include prolonged periods of
reported incid ence is p artly attribu ted to the d efinitions,
immobilization, poor nutrition, and corticosteroid therapy
associated with postoperative immunosuppression. Corti-
costeroids suppress osteoblast function, inhibit bone forma-
Table 5 1 .1 0 G a st roin t est in a l com p lica t ion s
tion, inhibit intestinal calcium absorption, and stimulate
follow in g h ea r t t ra n sp la n t a t ion
renal calcium excretion. These effects may lead to secondary
hyperparathyroidism w ith increased osteoclastic bone Risk Factor Complications
resorption, d ecreased production of skeletal grow th factors,
Immunosuppression
and alteration of the hypothalamic–pituitary–gonadal axis, Corticosteroids Peptic ulceration, bleeding, perforation,
resulting in hypogonadism. Postmenopausal w omen, chil- toxic megacolon, intestinal perforation,
dren, and patients 50 years of age are at greatest risk of pancreatitis
osteoporosis following heart transplantation; however, Cyclosporine Hepatocellular injury, cholelithiasis
almost all heart transplant recipients have some degree of Azathioprine Cholestatic/hepatocellular injury,
bone mineral d ensity loss (215). pancreatitis
The most rapid d emineralization occurs during the first 6 Mycophenolate mofetil Diarrhea, nausea, vomiting, abdominal
to 12 months follow ing transplantation, w ith less or no sub- pain
sequent bone loss thereafter (216–218). Some stud ies have Infection
demonstrated recovery of bone mineral density during the CMV Esophagitis, gastritis with gastric
second and third post-transplant years (219). The overall bleeding or ulceration, colitis, hepatitis
incidence of severe osteoporosis at 2 years following heart HSV Oral ulceration, esophagitis, colitis
transplantation w as 28% as m easured in the lum bar spine Adenovirus Colitis
Clostridium difficile Pseudomembranous colitis
and 20% by measurements from the femoral neck (217).
Salmonella Diarrhea
Fracture prevalence approximates 5% to 30% (220). Frac-
Candida albicans Pharyngitis, esophagitis
tures most commonly involve the spine and occur during the
first 6 months after transplantation. Women are at increased Post-transplant Bowel obstruction, perforation
lymphoproliferative disease
risk to sustain a fracture, perhaps because their pretransplant
bone mineral d ensity is low er than men. No pretransplant Adapted from Rayburn BK. Other long-term complications. In: Kirklin JK, Young JB,
biochemical or d ensitometric measurement reliably predicts McGiffin DC, eds. Heart transplantation: medicine, surgery, immunology, and research.
fracture in the individual patient. The amount of bone loss is New York, NY: Churchill Livingstone; 2002:Chapter 18, 693 (Tables 18 and 19).
w hich au thors u tilize to id entify p atients in retrosp ective only d iagnosed by end oscop ic p roced u res, ind icating an
review s. If one consid ers presentation of gastrointestinal ad van tage of end oscop y over bariu m stu d ies in these
sym p tom s requ iring investigation w ith end oscop y or bar- p atients. Tw en ty-th ree p atients (15%) u nd erw ent su rgical
ium enem a, as op p osed to id entifying patients by op erative p roced u res for gastroin testin al com p lication s w ith a 2.5%
events, the incid ence of gastrointestinal abnorm alities or m ortality.
com plications follow ing heart transp lantation m ay be as Gastrointestinal d isease follow ing heart transp lantation
high as 42% (225). N early tw o-third s of patients d evelop is thou ght to occu r as a consequ ence of (a) operation in
minor comp lications su ch as abd ominal p ain, nau sea, vom - d ebilitated p atients w ith sequ elae of long-stand ing heart
iting, d iarrhea, constipation, stom atitis, and reflu x d isease. failu re, (b) u tilization of card iop u lm onary bypass w ith
The m ajority of gastrointestinal com p lications occu r w ithin p otential for low flow states, and (c) the effects of postoper-
the first 3 to 5 years follow ing heart transplantation, w ith ative im m u nosu p p ression. Corticosteroid s have been asso-
70% occu rring w ithin 1 year. The greatest risk occu rs ciated w ith an increased risk of p ep tic u lceration, bow el
w ithin the first 30 d ays (223,224). At least one-half of these p erforation, gastrointestin al bleed ing, an d p ancreatitis.
com plications appear to requ ire operative intervention Sharm a et al. (224) observed a higher m aintenance d ose of
(224). p red nisone in p atients w ith gastrointestinal com plications
In a retrosp ective review of 240 heart transplant recip i- as com p ared w ith th ose p atien ts w ithou t gastroin testin al
ents from Decem ber 1985 to Ju ne 1994, Sharma et al. (224) com p lications (224). H ow ever, the relationship betw een
rep orted an incid ence of gastrointestinal com p lications in p u lse corticosteroid therap y and the onset of abd om inal
21 p atients (9.3%), w ith hep atobiliary (29%), pep tic u lcer com plications has not been consistently found am ong large
d isease (14%), and p ancreatic (14%) com plications being series of p atients. In ad d ition to corticosteroid s, other fac-
the m ost p revalent (224). Tw elve proced ures (63%) w ere tors that m ay in crease th e risk for gastroin testin al com -
either em ergently or urgently perform ed , and seven p roce- p lication s requ irin g a gen eral su rgical p roced u re inclu d e
d u res (37%) w ere carried ou t electively. The operative m or- a pretransplant d iagnosis of ischem ic card iom yopathy and
tality w as 33% in patients requ iring an em ergent or u rgent history of p reviou s abd om inal op eration (226).
intervention, w hile there w as no operative m ortality Gastrointestinal com p lications follow ing heart trans-
am ong those p atients w ho had an elective p roced u re. p lantation requ ire p rom p t and aggressive therapy to lim it
Au gu stine et al. (223) reported on 131 heart or heart-lu ng the d egree of m orbid ity and m ortality. The presence of
transp lant recip ients from Ju ly 1983 to Decem ber 1989. im m unosupp ression w ith higher d oses of steroid s in the
Tw enty-eight p atients (21%) had 38 gastrointestinal com - early p eriop erative p eriod m ay m ask the m anifestations of
plications that includ ed visceral perforations (6), gastrocu - gastrointestinal com p lications, thu s d elaying institu tion of
taneou s fistu la (1), retroperitoneal abscess (1), cholecystitis therap y. The m ortality of gastrointestinal com plications is
(5), gastric atony (1), perianal abscess (1), gastrointestinal greatest in the first 30 d ays follow ing heart transplantation
bleed ing (4), esophagitis (2), p ancreatitis (2), p ancreatic (226–228).
abscess (2), hep atitis (2), CMV infection (3), and d iarrhea
(8). Thirteen (46%) of 28 patients requ ired 17 operative p ro-
ced u res for treatm ent and inclu d ed cholecystectom y (5),
■ CONCLUSION
colon resection w ith colostom y (3), closu re of p erforated H eart transp lantation continu es to rem ain the m ost effica-
gastrod u od enal u lcer (3) and rep air of gastrocutaneou s fis- ciou s form of card iac rep lacem ent therap y for patients suf-
tu la (1), d rainage of pancreatic abscess (2), pylorop lasty (1), fering from ad vanced heart failu re. The p ast several
and incision and d rainage of perianal abscess (1). Age, gen- d ecad es have d em onstrated im p rovem ents in overall su r-
d er, race, and nu m ber of rejection episod es d id not corre- vival and a d ecreased incid ence of many of the com plica-
late w ith the occurrence of a gastrointestinal com plication. tions associated w ith heart transp lantation. Continued
Steck et al. (225) investigated the incid ence of gastrointesti- research and ad vances in the u nd erstand ing of the alloim -
nal com plications by review ing the ind ications and find - m u ne resp onse, im m u nosu p p ression strategies, im m u ne
ings of end oscopic and surgical proced ures involving the su rveillance, p atient selection, organ p reservation, and the
gastrointestinal tract in 159 heart transplant recip ients m anagem ent of long-term com p lications w ill likely lead to
(225). Sixty-seven patients (42%) had gastrointestinal continu ed im p roved ou tcomes.
sym p tom s significant enou gh to w arrant either end o-
scop ic, rad iologic, or surgical proced ures. Forty-seven
patients (30%) u nd erw ent esophagogastrod u od enoscop y ■ REFERENCES
or u p p er gastrointestinal roentgenograp hy that d em on- 1. H unt SA, et al. ACC/ AH A 2005 Gu id eline Up d ate for the Diagnosis
strated a high p revalence of esophagitis, gastritis, d u od eni- and Managem ent of Chronic H eart Failu re in the Ad u lt: a report of the
Am erican College of Card iology/ Am erican H eart Association Task
tis, and gastrod u od enal u lcers. Thirty-tw o p atients (20%) Force on Practice Gu id elines (Writing Com m ittee to Up d ate the 2001
u nd erw ent bariu m enem a or end oscop ic p roced u res of Gu id elines for the Evalu ation and Managem ent of H eart Failu re):
the low er gastrointestinal tract, w ith the m ost frequ ent d evelop ed in collaboration w ith the Am erican College of Chest Physi-
cians and the International Society for H eart and Lung Transplanta-
find ings being benign p olyp s and colitis. Op p ortu nistic tion: end orsed by the H eart Rhythm Society. Circulation 2005;112(12):
infections, esp ecially w ith CMV, w ere frequ ent and w ere e154–e235.
2. Taylor DO, et al. Registry of the International Society for H eart and 27. Brand t M, et al. Influence of bicaval anastom oses on late occu rrence of
Lu ng Transp lantation: tw enty-sixth official ad u lt heart transp lant atrial arrhythm ia after heart transp lantation. Ann Thorac Surg
rep ort—2009. J Heart Lung Transplant 2009;28(10):1007–1022. 1997;64(1):70–72.
3. Taylor DO, et al. Registry of the International Society for H eart and 28. Milano CA, et al. Evalu ation of early p ostop erative resu lts after
Lu ng Transp lantation: tw enty-fifth official ad u lt heart transp lant bicaval versu s stand ard card iac transp lantation and review of the lit-
rep ort—2008. J Heart Lung Transplant 2008;27(9):943–956. eratu re. Am Heart J 2000;140(5):717–721.
4. Taylor DO, et al. Registry of the International Society for H eart and 29. Borkon AM, Kao A, Stuart S, et al. Biatrial im p lantation w ith m od ified
Lu ng Transp lantation: tw enty-fou rth official ad u lt heart transp lant cabrol technique provid es sim ilar outcom es com pared to bicaval
rep ort—2007. J Heart Lung Transplant 2007;26(8):769–781. anastom osis. J Heart Lung Transplant 2009;28(2):S191 (abstract).
5. Marelli D, et al. Seventeen-year exp erience w ith 1,083 heart trans- 30. Cu i G, et al. Increased incid ence of atrial flu tter associated w ith the
p lants at a single institu tion. Ann Thorac Surg 2002;74(5):1558–1566; rejection of heart transp lantation. Am J Cardiol 2001;88(3):280–284.
d iscussion 1567. 31. Scott CD, Dark JH , McCom b JM. Arrhythm ias after card iac transp lan-
6. Pagani FD, et al. Extend ed m echanical circu latory su p p ort w ith a con- tation. Am J Cardiol 1992;70(11):1061–1063.
tinuou s-flow rotary left ventricu lar assist d evice. J Am Coll Cardiol 32. Jacqu et L, et al. Card iac rhythm d istu rbances early after orthotop ic
2009;54(4):312–321. heart transplantation: prevalence and clinical im p ortance of the
7. Miller LW, et al. Use of a continu ou s-flow d evice in p atients aw aiting observed abnorm alities. J Am Coll Cardiol 1990;16(4):832–837.
heart transplantation. N Engl J Med 2007;357(9):885–896. 33. Ahm ari SA, et al. Prevalence, p athop hysiology, and clinical signifi-
8. Aggarw al S, Pagani FD. Brid ge to transp lantation: cu rrent outcom es. cance of post-heart transp lant atrial fibrillation and atrial flu tter.
J Card Surg 2010;25(4):455–461. J Heart Lung Transplant 2006;25(1):53–60.
9. Slau gh ter MS, et al. Ad vanced h eart failu re treated w ith con tin u - 34. Tahara K, et al. The significance of atrial m onop hasic action p otentials
ou s-flow left ven tricu lar assist d evice. N Engl J Med 2009;361(23): for m onitoring rat card iac allograft rejection. J Heart Lung Transplant
2241–2251. 1998;17(10):954–958.
10. Kirklin JK, et al. Evolving trend s in risk p rofiles and cau ses of d eath 35. Pavri BB, et al. Prevalence and p rognostic significance of atrial
after heart transp lantation: a ten-year m u lti-institu tional stu d y. J Tho- arrhythm ias after orthotop ic card iac transp lantation. J Am Coll Cardiol
rac Cardiovasc Surg 2003;125(4):881–890. 1995;25(7):1673–1680.
11. You ng JB, et al. Determ inants of early graft failu re follow ing card iac 36. Casted o E, et al. Left atrial throm bosis after h eart tran sp lan tation.
transp lantation, a 10-year, m u lti-institu tional, m u ltivariable analysis. Cardiovasc Surg 2003;11(3):247–249.
J Heart Lung Transplant 2001;20(2):212. 37. Deru m eau x G, et al. Stand ard orthotop ic heart transp lantation versu s
12. Jahania MS, et al. Acu te allograft failu re in thoracic organ transp lanta- total orthotop ic heart transp lantation. A transesop hageal echocard io-
tion. J Card Surg 2000;15(2):122–128. grap hy stu d y of the incid ence of left atrial throm bosis. Circulation
13. N aftel DC, Brow n RN . Su rvival after heart transp lantation. In: Kirklin 1995;92(9 Su p pl):II196–II201.
JK, You ng JB, McGiffin DC, ed s. Heart transplantation: medicine, sur- 38. Sahar G, et al. Etiological factors influ encing the d evelop m ent of atri-
gery, immunology, and research. N ew York, N Y: Chu rchill Livingstone; oventricu lar valve incom p etence after heart transp lantation. Trans-
2002:587–614. plant Proc 1997;29(6):2675–2676.
14. Bittner H B, et al. Right ventricu lar d ysfu nction after card iac trans- 39. De Sim one R, et al. Atrioventricu lar valve insu fficiency and atrial
p lantation: p rim arily related to statu s of d onor heart. Ann Thorac Surg geom etry after orthotop ic heart transp lantation. Ann Thorac Surg
1999;68(5):1605–1611. 1995;60(6):1686–1693.
15. Bittner H B, et al. Brain d eath alters card iop u lm onary hem od ynam ics 40. Law Y, et al. Su pram itral valve obstru ction from hyp ertrop hied native
and im pairs right ventricu lar p ow er reserve against an elevation of atrial tissu e as a com plication of orthotop ic heart transp lantation.
p u lm onary vascu lar resistance. Chest 1997;111(3):706–711. J Heart Lung Transplant 1997;16(9):922–925.
16. Bittner H B, et al. Preload -recru itable stroke w ork relationships and 41. Oaks TE, et al. Acquired cor triatriatu m after orthotop ic card iac trans-
d iastolic d ysfu nction in the brain-d ead organ d onor. Circulation plantation. Ann Thorac Surg 1995;59(3):751–753.
1996;94(9, Su ppl):II320–II325. 42. Dreyfu s G, et al. Kinking of the p u lm onary artery: a treatable cau se of
17. Mu rali S, et al. Preop erative p u lm onary hem od ynam ics and early acute right ventricu lar failu re after heart transp lantation. J Heart
m ortality after orthotopic card iac transp lantation: the Pittsburgh Transplant 1990;9(5):575–576.
experience. Am Heart J 1993;126(4):896–904. 43. Laske A, et al. Mod ified op eration techniqu e for orthotop ic heart
18. Chen JM, et al. Reevalu ating the significance of p u lm onary hyp erten- transp lantation. Eur J Cardiothorac Surg 1995;9(3):120–126.
sion before card iac transp lantation: d eterm ination of op tim al thresh- 44. Defraigne JO, et al. Aneu rysm of the ascend ing aorta after card iac
old s and quantification of the effect of reversibility on perioperative transp lantation. Ann Thorac Surg 1992;54(5):983–984.
m ortality. J Thorac Cardiovasc Surg 1997;114(4):627–634. 45. Low er RR, Stofer RC, Shu m w ay N E. H om ovital transp lantation of the
19. Chen EP, et al. Effects of nitric oxid e after card iac transp lantation in heart. J Thorac Cardiovasc Surg 1961;41:196–204.
the setting of recip ient p u lm onary hyp ertension. Ann Thorac Surg 46. Sievers H H , et al. An alternative techniqu e for orthotop ic card iac
1997;63(6):1546–1555. transplantation, w ith p reservation of the norm al anatom y of the right
20. H olt N D, McCom b JM. Card iac transp lantation and p acem akers: atrium . Thorac Cardiovasc Surg 1991;39(2):70–72.
w hen and w hat to im p lant. Card Electrophysiol Rev 2002;6(1/ 2): 47. Traversi E, et al. The bicaval anastom osis techniqu e for orthotop ic
140–151. heart transplantation yield s better atrial function than the stand ard
21. Miyam oto Y, et al. Brad yarrh ythm ia after heart tran sp lantation . technique: an echocard iographic autom atic bou nd ary d etection
Incid ence, tim e cou rse, and ou tcom e. Circulation 1990;82(5 Su p p l): stu d y. J Heart Lung Transplant 1998;17(11):1065–1074.
IV313–IV317. 48. Weiss ES, et al. Ou tcom es in bicaval versu s biatrial techniqu es in heart
22. Cantillon DJ, et al. Long-term ou tcom es and clinical p red ictors for transplantation: an analysis of the UN OS d atabase. J Heart Lung Trans-
p acem aker-requiring brad yarrhythm ias after card iac transp lantation: plant 2008;27(2):178–183.
analysis of the UN OS/ OPTN card iac transp lant d atabase. Heart 49. Meyer SR, et al. Declining need for p erm anent p acem aker insertion
Rhythm 2010;7(11):1567–1571. w ith the bicaval techniqu e of orthotop ic heart transp lantation. Can J
23. Cantillon DJ, et al. Long-term ou tcom es and clinical p red ictors for Cardiol 2005;21(2):159–163.
p acing after card iac transp lantation. J Heart Lung Transplant 2009; 50. Park KY, et al. Bicaval anastom osis red uces tricuspid regurgitation
28(8): 791–798. after heart transplantation. Asian Cardiovasc Thorac Ann 2005;13(3):
24. DiBiase A, et al. Frequ ency and m echanism of brad ycard ia in card iac 251–254.
transp lant recipients and need for p acem akers. Am J Cardiol 1991; 51. Jeevanand am V, et al. Donor tricu sp id annu lop lasty d u ring ortho-
67(16):1385–1389. topic heart transplantation: long-term resu lts of a prosp ective con-
25. Raghavan C, et al. Long-term follow -u p of heart transp lant recipients trolled stu d y. Ann Thorac Surg 2006;82(6):2089–2095; d iscu ssion 2095.
requ iring perm anent p acem akers. J Heart Lung Transplant 1995;14(6 Pt 52. Aziz TM, et al. Risk factors for tricuspid valve regurgitation after ortho-
1):1081–1089. topic heart transplantation. Ann Thorac Surg 1999;68(4):1247–1251.
26. Blanche C, et al. H eart transp lantation w ith bicaval and p u lm onary 53. Aziz T, et al. Bicaval and stand ard techniqu es in orthotop ic heart
venou s anastom oses. A hem od ynam ic analysis of the first 117 patients. transplantation: m ed iu m -term experience in card iac perform ance and
J Cardiovasc Surg (Torino) 1997;38(6):561–566. su rvival. J Thorac Cardiovasc Surg 1999;118(1):115–122.
54. Solom on N A, et al. Biatrial or bicaval techniqu e for orthotopic heart 78. Torry RJ, et al. Vascu lar end othelial grow th factor exp ression in trans-
transplantation: w hich is better? Heart Lung Circ 2004;13(4):389–394. planted hu m an hearts. Transplantation 1995;60(12):1451–1457.
55. Wong RC, et al. Tricu sp id regu rgitation after card iac transp lantation: 79. Van H offen E, et al. In situ exp ression of cytokines in hu m an heart
an old problem revisited . J Heart Lung Transplant 2008;27(3):247–252. allografts. Am J Pathol 1996;149(6):1991–2003.
56. Aziz TM, et al. Clinical significance of tricu sp id valve d ysfu nction 80. Deng MC, et al. Card iac allograft vascu lar d isease. Relationship to
after orthotopic heart transp lantation. J Heart Lung Transplant m icrovascu lar cell surface m arkers and inflam m atory cell phenotypes
2002;21(10):1101–1108. on end om yocard ial biop sy. Circulation 1995;91(6):1647–1654.
57. Brow n N E, et al. Tricu sp id annu lop lasty significantly red u ces early 81. Ohtani H , et al. Intercellu lar ad hesion m olecu le-1 ind u ction: a sensi-
tricu sp id regurgitation after biatrial heart transp lantation. J Heart tive and qu antitative m arker for card iac allograft rejection. J Am Coll
Lung Transplant 2004;23(10):1160–1162. Cardiol 1995;26(3):793–799.
58. Young JB, et al. Matching the heart d onor and heart transp lant recip i- 82. H erskow itz A, et al. Patterns of m yocard ial cell ad hesion m olecu le
ent. Clu es for su ccessfu l exp ansion of the d onor p ool: a m ultivariable, expression in hum an end om yocard ial biopsies after card iac trans-
m u ltiinstitu tional rep ort. The Card iac Transp lant Research Database plantation. Ind u ced ICAM-1 and VCAM-1 related to im p lantation
Grou p. J Heart Lung Transplant 1994;13(3):353–364; d iscu ssion and rejection. Am J Pathol 1994;145(5):1082–1094.
364–365. 83. Briscoe DM, et al. Pred ictive valu e of ind u cible end othelial cell ad he-
59. Kirklin JK, et al. Cu rrent ou tcom es follow ing heart transp lantation. sion m olecu le exp ression for acu te rejection of hu m an card iac allo-
Semin Thorac Cardiovasc Surg 2004;16(4):395–403. grafts. Transplantation 1995;59(2):204–211.
60. Ku bo SH , et al. Risk factors for late recu rrent rejection after heart 84. Qiao JH , et al. Expression of cell ad hesion m olecu les in hu m an card iac
transplantation: a m u ltiinstitu tional, m u ltivariable analysis. Card iac allograft rejection. J Heart Lung Transplant 1992;11(5):920–925.
Transplant Research Database Group. J Heart Lung Transplant 1995;14(3): 85. Ferran C, et al. Implications of de novo ELAM-1 and VCAM-1 expression
409–418. in human cardiac allograft rejection. Transplantation 1993;55(3):605–609.
61. Miller LW. Long-term com p lications of card iac transp lantation. Prog 86. Tanio JW, et al. Differential exp ression of the cell ad hesion m olecu les
Cardiovasc Dis 1991;33(4):229–282. ICAM-1, VCAM-1, and E-selectin in norm al and p osttransp lantation
62. Winters GL, et al. Pred ictors of late acu te orthotop ic heart transp lant m yocard iu m . Cell ad hesion m olecu le exp ression in hu m an card iac
rejection. Circulation 1989;80(5 Pt 2):III106–III110. allografts. Circulation 1994;89(4):1760–1768.
63. Jarcho J, et al. Influ ence of H LA m ism atch on rejection after heart 87. Melter M, et al. Expression of the chem okine recep tor CXCR3 and its
transplantation: a m u ltiinstitu tional stu d y. The Card iac Transp lant ligand IP-10 d u ring hu m an card iac allograft rejection. Circulation
Research Database Grou p . J Heart Lung Transplant 1994;13(4):583–595; 2001;104(21):2558–2564.
d iscussion 595–596. 88. Zhao DX, et al. Differential exp ression of the IFN -gam m a-ind u cible
64. De Mattos AM, et al. H LA–DR m ism atching correlates w ith early car- CXCR3-bind ing chem okines, IFN -ind u cible p rotein 10, m onokine
d iac allograft rejection, incid ence, and graft su rvival w hen high-confi- ind u ced by IFN , and IFN -ind u cible T cell alp ha chem oattractant in
d ence-level serological DR typ ing is u sed . Transplantation 1994;57(4): hum an card iac allografts: association w ith card iac allograft vascu-
626–630. lop athy and acu te rejection. J Immunol 2002;169(3):1556–1560.
65. Kobashigaw a JA, et al. Pretransp lant p anel reactive-antibod y screens. 89. Fahm y N M, et al. Chem okine and recep tor-gene exp ression d u ring
Are they truly a m arker for p oor outcom e after card iac transplanta- early and late acute rejection episod es in hum an card iac allografts.
tion? Circulation 1996;94(9 Su p p l):II294–II297. Transplantation 2003;75(12):2044–2047.
66. George JF, et al. Utility of p osttransp lantation panel-reactive antibod y 90. Fahm y N M, et al. Chem okine and chem okine recep tor gene exp res-
m easurem ents for the pred iction of rejection frequency and survival of sion ind icates acu te rejection of hu m an card iac transp lants. Transplan-
heart transplant recipients. J Heart Lung Transplant 1995;14(5):856–864. tation 2003;75(1):72–78.
67. Lavee J, et al. Influ ence of p anel-reactive antibod y and lym phocyto- 91. Reed EF, et al. Acute antibod y-m ed iated rejection of card iac trans-
toxic crossm atch on su rvival after heart transp lantation. J Heart Lung p lants. J Heart Lung Transplant 2006;25(2):153–159.
Transplant 1991;10(6):921–929; d iscu ssion 929–930. 92. Taylor DO, et al. Allograft coronary artery d isease: clinical correla-
68. Loh E, et al. Role of p anel-reactive antibod y cross-reactivity in p re- tions w ith circu lating anti-H LA antibod ies and the im m u no-
d icting su rvival after orthotop ic heart transp lantation. J Heart Lung histop athologic pattern of vascu lar rejection. J Heart Lung Transplant
Transplant 1994;13(2):194–201. 2000;19(6):518–521.
69. Michaels PJ, et al. H u m oral rejection in card iac transp lantation: risk 93. Lones MA, et al. Clinical-p athologic featu res of hu m oral rejection in
factors, hem od ynam ic consequ ences and relationship to transp lant card iac allografts: a stu d y in 81 consecu tive p atients. J Heart Lung
coronary artery d isease. J Heart Lung Transplant 2003;22(1):58–69. Transplant 1995;14(1 Pt 1):151–162.
70. N w akanm a LU, et al. Influ ence of p retransp lant p anel-reactive anti- 94. Sethi GK, et al. Is it necessary to p erform su rveillance end om yocard ial
bod y on outcom es in 8,160 heart transplant recip ients in recent era. biop sies in heart transp lant recip ients? J Heart Lung Transplant 1995;
Ann Thorac Surg 2007;84(5):1556–1562; d iscu ssion 1562–1563. 14(6 Pt 1):1047–1051.
71. Itescu S, et al. Preform ed IgG antibod ies against m ajor histocom p ati- 95. White JA, et al. Routine su rveillance m yocard ial biop sies are u nneces-
bility com plex class II antigens are m ajor risk factors for high-grad e sary beyond one year after heart transp lantation. J Heart Lung Trans-
cellular rejection in recip ients of heart transp lantation. Circulation plant 1995;14(6 Pt 1):1052–1056.
1998;98(8):786–793. 96. Sharples LD, et al. Error rates w ith w hich end om yocard ial biop sy
72. Kobashigaw a J, et al. Rep ort from a consensu s conference on the sen- sp ecim ens are grad ed for rejection after card iac transp lantation. Am J
sitized patient aw aiting heart transp lantation. J Heart Lung Transplant Cardiol 1992;70(4):527–530.
2009;28(3):213–225. 97. N ielsen H , et al. Rep rod u cibility of the acu te rejection d iagnosis in
73. Stehlik J, et al. Utility of virtu al crossm atch in sensitized p atients hu m an card iac allografts. The Stanford Classification and the Interna-
aw aiting heart transp lantation. J Heart Lung Transplant 2009;28(11): tional Grad ing System . J Heart Lung Transplant 1993;12(2):239–243.
1129–1134. 98. Deng MC, et al. N oninvasive d iscrim ination of rejection in card iac
74. Stew art S, et al. Revision of the 1990 w orking form u lation for the stan- allograft recip ients using gene exp ression p rofiling. Am J Transplant
d ard ization of nom enclatu re in the d iagnosis of heart rejection. J Heart 2006;6(1):150–160.
Lung Transplant 2005;24(11):1710–1720. 99. Starling RC, et al. Molecu lar testing in the m anagem ent of card iac
75. Billingham ME, et al. A w orking form u lation for the stand ard ization transp lant recip ients: initial clinical exp erience. J Heart Lung Trans-
of nom enclature in the d iagnosis of heart and lu ng rejection: H eart plant 2006;25(12):1389–1395.
Rejection Stu d y Grou p . The International Society for H eart Transplan- 100. Mehra MR, et al. Clinical im p lications and longitu d inal alteration of
tation. J Heart Transplant 1990;9(6):587–593. p erip heral blood transcriptional signals ind icative of fu tu re card iac
76. Rod riguez ER. The p athology of heart transp lant biop sy sp ecim ens: allograft rejection. J Heart Lung Transplant 2008;27(3):297–301.
revisiting the 1990 ISH LT w orking form u lation. J Heart Lung Trans- 101. Pham MX, et al. Gene-exp ression p rofiling for rejection su rveillance
plant 2003;22(1):3–15. after card iac transp lantation. N Engl J Med 362(20):1890–1900.
77. Ruan XM, et al. Cytokine exp ression and end othelial cell and lym pho- 102. Pham MX, et al. Molecu lar testing for long-term rejection su rveillance
cyte activation in hu m an card iac allograft rejection: an im m u nohisto- in heart transplant recipients: d esign of the Invasive Monitoring
chem ical stu d y of end om yocard ial biop sy sam p les. J Heart Lung Attenu ation Throu gh Gene Exp ression (IMAGE) trial. J Heart Lung
Transplant 1992;11(6):1110–1115. Transplant 2007;26(8):808–814.
103. Kobashigaw a JA, et al. Benefit of im m u ne m onitoring in heart trans- 132. Kapad ia SR, et al. Developm ent of transplantation vasculopathy and
p lant p atients u sing ATP p rod u ction in activated lym p hocytes. J Heart progression of d onor-transm itted atherosclerosis: com parison by serial
Lung Transplant 29(5):504–508. intravascular ultrasound im aging. Circulation 1998;98(24):2672–2678.
104. Mancini D, et al. Use of rap am ycin slow s p rogression of card iac trans- 133. Gou ld DS, Au chincloss H Jr. Direct and ind irect recognition: the role
p lantation vascu lopathy. Circulation 2003;108(1):48–53. of MH C antigens in graft rejection. Immunol Today 1999;20(2):77–82.
105. Eisen H J, et al. Everolim u s for the p revention of allograft rejection and 134. Avery RK. Viral triggers of card iac-allograft d ysfu nction. N Engl J Med
vasculopathy in card iac-transplant recipients. N Engl J Med 2003;349(9): 2001;344(20):1545–1547.
847–858. 135. You ng JB. Allograft vascu lop athy: d iagnosing the nem esis of heart
106. De Marco T, et al. Su ccessfu l im m u nom od u lation w ith intravenous transp lantation. Circulation 1999;100(5):458–460.
gam m a globu lin and cyclop hosp ham id e in an alloim m u nized heart 136. Mehra MR, et al. The prognostic im p act of im m u nosu p p ression and
transplant recip ient. J Heart Lung Transplant 1997;16(3):360–365. cellular rejection on card iac allograft vascu lopathy: tim e for a reap-
107. Miller LW, et al. Infection after heart transp lantation: a m u ltiinstitu - p raisal. J Heart Lung Transplant 1997;16(7):743–751.
tional stu d y. Card iac Transp lant Research Database Grou p . J Heart 137. Kobashigaw a JA, et al. Does acu te rejection correlate w ith the d evel-
Lung Transplant 1994;13(3):381–392; d iscu ssion 393. op m ent of transp lant coronary artery d isease? A m u lticenter stu d y
108. H unt SA, Current status of card iac transplantation. JAMA 1998;280(19): u sing intravascular u ltrasou nd . Sand oz/ CVIS Investigators. J Heart
1692–1698. Lung Transplant 1995;14(6 Pt 2):S221–S226.
109. H u nt SA, H ad d ad F. The changing face of heart transp lantation. J Am 138. Stovin PG, et al. Lack of association betw een end om yocard ial evi-
Coll Cardiol 2008;52(8):587–598. d ence of rejection in the first six m onths and the later d evelop m ent of
110. Robbins RC, et al. Thirty years of card iac transp lantation at Stanford transp lant-related coronary artery d isease. J Heart Lung Transplant
u niversity. J Thorac Cardiovasc Surg 1999;117(5):939–951. 1993;12(1 Pt 1):110–116.
111. Fishm an JA, Ru bin RH . Infection in organ-transp lant recip ients. N 139. Liu Z, et al. Contribu tion of d irect and ind irect recognition p athw ays
Engl J Med 1998;338(24):1741–1751. to T cell alloreactivity. J Exp Med 1993;177(6):1643–1650.
112. Fishm an JA. Infection in solid -organ transp lant recip ients. N Engl J 140. Liu Z, et al. Ind irect recognition of d onor H LA–DR p ep tid es in organ
Med 2007;357(25):2601–2614. allograft rejection. J Clin Invest 1996;98(5):1150–1157.
113. H ad d ad F, et al. Changing trend s in infectiou s d isease in heart trans- 141. Tu gu lea S, et al. N ew strategies for early d iagnosis of heart allograft
p lantation. J Heart Lung Transplant 29(3):306–315. rejection. Transplantation 1997;64(6):842–847.
114. Sm art FW, et al. Risk factors for early, cu m u lative, and fatal infections 142. Vand erlu gt CJ, Miller SD. Ep itop e sp read ing. Curr Opin Immunol
after heart transp lantation: a m u ltiinstitu tional stu d y. J Heart Lung 1996;8(6):831–836.
Transplant 1996;15(4):329–341. 143. Rose EA, et al. Relation of H LA antibod ies and graft atherosclerosis in
115. Macd onald PS, et al. A d ou ble-blind p lacebo-controlled trial of low - hum an card iac allograft recip ients. J Heart Lung Transplant 1992;11(3
d ose ganciclovir to p revent cytom egaloviru s d isease after heart trans- Pt 2):S120–S123.
p lantation. J Heart Lung Transplant 1995;14(1 Pt 1):32–38. 144. Reed EF, et al. Monitoring of solu ble H LA alloantigens and anti-H LA
116. Potena L, Valantine H A. Cytom egaloviru s-associated allograft rejec- antibod ies id entifies heart allograft recipients at risk of transplant-
tion in heart transp lant p atients. Curr Opin Infect Dis 2007;20(4): associated coronary artery d isease. Transplantation 1996;61(4):566–572.
425–431. 145. Du nn MJ, et al. Anti-end othelial antibod ies and coronary artery d is-
117. Potena L, et al. Prophylaxis versu s p reem p tive anti-cytom egaloviru s ease after card iac transp lantation. Lancet 1992;339(8809):1566–1570.
ap proach for prevention of allograft vascu lop athy in heart transplant 146. Rickenbacher PR, et al. Coronary artery intim al thickening in the
recipients. J Heart Lung Transplant 2009;28(5):461–467. transplanted heart. An in vivo intracoronary u ltrasou nd stu d y of
118. Montoya JG, et al. Infectiou s com p lications am ong 620 consecutive im m unologic and m etabolic risk factors. Transplantation 1996;61(1):
heart transplant patients at Stanford University Med ical Center. Clin 46–53.
Infect Dis 2001;33(5):629–640. 147. Low ry RW, et al. What are the im p lications of card iac infection w ith
119. Ru bin RH . Prevention and treatm ent of cytom egaloviru s d isease in cytom egalovirus before heart transplantation? J Heart Lung Transplant
heart transp lant patients. J Heart Lung Transplant 2000;19(8):731–735. 1994;13(1 Pt 1):122–128.
120. Potena L, et al. Acu te rejection and card iac allograft vascu lar d isease is 148. Mehra MR, et al. International Society for H eart and Lu ng Transp lan-
red u ced by suppression of subclinical cytom egalovirus infection. tation w orking form u lation of a stand ard ized nom enclatu re for car-
Transplantation 2006;82(3):398–405. d iac allograft vascu lopathy—2010. J Heart Lung Transplant 29(7):
121. Kalil AC, et al. Meta-analysis: the efficacy of strategies to prevent 717–727.
organ d isease by cytom egaloviru s in solid organ transp lant recip i- 149. Mehra MR, et al. The prognostic significance of intim al p roliferation
ents. Ann Intern Med 2005;143(12):870–880. in card iac allograft vascu lop athy: a p arad igm shift. J Heart Lung Trans-
122. H od son EM, et al. Antiviral m ed ications to p revent cytom egaloviru s plant 1995;14(6 Pt 2):S207–S211.
d isease and early d eath in recip ients of solid -organ transp lants: a sys- 150. Tuzcu EM, et al. Intravascu lar u ltrasou nd evid ence of angiograp hi-
tem atic review of rand om ised controlled trials. Lancet 2005;365(9477): cally silent progression in coronary atherosclerosis p red icts long-term
2105–2115. m orbid ity and m ortality after card iac transp lantation. J Am Coll Car-
123. Merigan TC, et al. A controlled trial of ganciclovir to prevent diol 2005;45(9):1538–1542.
cytom egalovirus d isease after heart transp lantation. N Engl J Med 151. Kobashigaw a JA, et al. Mu lticenter intravascu lar u ltrasou nd valid a-
1992;326(18):1182–1186. tion stu d y am ong heart transp lant recip ients: ou tcom es after five
124. Wed em eyer H , et al. Long-term ou tcom e of chronic hep atitis B in years. J Am Coll Cardiol 2005;45(9):1532–1537.
heart transp lant recipients. Transplantation 1998;66(10):1347–1353. 152. Kao J, et al. Elevated seru m levels of the CXCR3 chem okine ITAC are
125. Wachs ME, et al. The risk of transm ission of hep atitis B from associated w ith the d evelopm ent of transp lant coronary artery d is-
H BsAg( ), H BcAb( ), H BIgM( ) organ d onors. Transplantation 1995; ease. Circulation 2003;107(15):1958–1961.
59(2):230–234. 153. Mehra MR, et al. An intravascu lar u ltrasou nd stu d y of the influ ence
126. Lake KD, et al. Ou tcom es of hep atitis C p ositive (H CV ) heart trans- of angiotensin-converting enzym e inhibitors and calcium entry block-
p lant recip ients. Transplant Proc 1997;29(1/ 2):581–582. ers on the d evelopm ent of card iac allograft vascu lop athy. Am J Cardiol
127. Ong JP, et al. Outcom e of d e novo hep atitis C viru s infection in heart 1995;75(12):853–854.
transplant recip ients. Hepatology 1999;30(5):1293–1298. 154. Lam ich R, et al. Efficacy of au gm ented im m u nosu p p ressive therap y
128. Israelski DM, Rem ington JS. Toxop lasm osis in the non-AIDS for early vascu lopathy in heart transp lantation. J Am Coll Cardiol
im m unocom prom ised host. Curr Clin Top Infect Dis 1993;13:322–356. 1998;32(2):413–419.
129. Luft BJ, Billingham M, Rem ington JS. End om yocard ial biop sy in the 155. Schroed er JS, et al. A prelim inary stu d y of d iltiazem in the p revention
d iagnosis of toxop lasm ic m yocard itis. Transplant Proc 1986;18(6): of coronary artery d isease in heart-transp lant recip ients. N Engl J Med
1871–1873. 1993;328(3):164–170.
130. Wreghitt TG, et al. Efficacy of p yrim etham ine for the p revention of 156. Kobashigaw a JA, et al. Effect of p ravastatin on ou tcom es after card iac
d onor-acqu ired Toxoplasma gondii infection in heart and heart-lung transplantation. N Engl J Med 1995;333(10):621–627.
transplant patients. Transpl Int 1992;5(4):197–200. 157. Wenke K, et al. Sim vastatin red u ces graft vessel d isease and m ortality
131. Schm auss D, Weis M. Card iac allograft vascu lop athy: recent d evelop - after heart transplantation: a fou r-year rand om ized trial. Circulation
m ents. Circulation 2008;117(16):2131–2141. 1997;96(5):1398–1402.
158. Marx SO, et al. Rap am ycin-FKBP inhibits cell cycle regu lators of p ro- 187. And oh TF, Bu rd m ann EA, Bennett WM. N ep hrotoxicity of im m u no-
liferation in vascu lar sm ooth m u scle cells. Circ Res 1995;76(3):412–417. su p pressive d ru gs: exp erim ental and clinical observations. Semin
159. Poon M, et al. Rap am ycin inhibits vascu lar sm ooth m u scle cell m igra- Nephrol 1997;17(1):34–45.
tion. J Clin Invest 1996;98(10):2277–2283. 188. Grieff M, et al. Cyclosp orine-ind u ced elevation in circu lating
160. Sehgal SN . Rap am u ne (RAPA, rap am ycin, sirolim u s): m echanism of end othelin-1 in patients w ith solid -organ transp lants. Transplantation
action im m u nosu p p ressive effect resu lts from blockad e of signal 1993;56(4):880–884.
transd u ction and inhibition of cell cycle p rogression. Clin Biochem 189. Ju lien J, et al. Cyclosp orine-ind u ced stim u lation of the renin–
1998;31(5):335–340. angiotensin system after liver and heart transp lantation. Transplanta-
161. Poston RS, et al. Rap am ycin reverses chronic graft vascu lar d isease in tion 1993;56(4):885–891.
a novel card iac allograft m od el. Circulation 1999;100(1):67–74. 190. Feutren G, Mihatsch MJ. Risk factors for cyclosp orine-ind u ced
162. Gallo R, et al. Inhibition of intim al thickening after balloon angio- nephrop athy in p atients w ith au toim m u ne d iseases. International
p lasty in porcine coronary arteries by targeting regu lators of the cell Kid ney Biop sy Registry of Cyclosp orine in Au toim m u ne Diseases.
cycle. Circulation 1999;99(16):2164–2170. N Engl J Med 1992;326(25):1654–1660.
163. Sousa JE, et al. Lack of neointim al p roliferation after im p lantation of 191. You ng EW, et al. A p rosp ective stu d y of renal stru ctu re and fu nction
sirolim u s-coated stents in hu m an coronary arteries: a qu antitative in psoriasis p atients treated w ith cyclosp orin. Kidney Int 1994;46(4):
coronary angiography and three-d im ensional intravascular ultra- 1216–1222.
sound stu d y. Circulation 2001;103(2):192–195. 192. Waser M, et al. Irreversibility of cyclosp orine-ind u ced renal fu nction
164. Lu o Y, et al. Rap am ycin resistance tied to d efective regu lation of im p airm ent in heart transp lant recip ients. J Heart Lung Transplant
p 27Kip 1. Mol Cell Biol 1996;16(12):6744–6751. 1993;12(5):846–850.
165. Marx SO, Marks AR. Bench to bed sid e: the d evelop m ent of rap am ycin 193. Vossler MR, et al. Pre-op erative renal fu nction p red icts d evelop m ent
and its app lication to stent restenosis. Circulation 2001;104(8):852–855. of chronic renal insu fficiency after orthotop ic heart transp lantation.
166. Kahan BD, et al. Im m u nosu p p ressive effects and safety of a J Heart Lung Transplant 2002;21(8):874–881.
sirolim us/ cyclosporine com bination regim en for renal transplanta- 194. Falkenhain ME, Cosio FG, Sed m ak DD. Progressive histologic inju ry
tion. Transplantation 1998;66(8):1040–1046. in kid neys from heart and liver transplant recipients receiving
167. Groth CG, et al. Sirolim u s (rap am ycin)-based therap y in hu m an renal cyclosp orine. Transplantation 1996;62(3):364–370.
transplantation: sim ilar efficacy and d ifferent toxicity com pared w ith 195. Fu rlan u t M, et al. Effect of flu ctu ation s of blood cyclosp orin e
cyclosp orine. Sirolim u s Eu rop ean Renal Transp lant Stu d y Grou p . con cen tration s on ren al fu n ction . Transplant Proc 1994;26(5):
Transplantation 1999;67(7):1036–1042. 2574–2575.
168. Raichlin E, et al. Conversion to sirolim u s as p rim ary im m u nosu p p res- 196. Chan C, et al. A rand om ized controlled trial of verap am il on
sion attenuates the progression of allograft vascu lopathy after card iac cyclosporine nephrotoxicity in heart and lung transplant recipients.
transplantation. Circulation 2007;116(23):2726–2733. Transplantation 1997;63(10):1435–1440.
169. H unt SA. Malignancy in organ transp lantation: heart. Transplant Proc 197. Pascu al M, et al. Strategies to im p rove long-term ou tcom es after renal
2002;34(5):1874–1876. transp lantation. N Engl J Med 2002;346(8):580–590.
170. Penn I. Incid ence and treatm ent of neop lasia after transp lantation. 198. Pascual M, et al. A prospective, randomized clinical trial of cyclosporine
J Heart Lung Transplant 1993;12(6 Pt 2):S328–S336. reduction in stable patients greater than 12 months after renal trans-
171. H ald as J, Wang W, Lazarchick J. Post-transp lant lym p hop roliferative p lantation. Transplantation 2003;75(9):1501–1505.
d isord ers: T-cell lym p hom a follow ing card iac transp lant. Leuk Lym- 199. Bestetti R, et al. Sw itch from calcineu rin inhibitors to sirolim u s-
phoma 2002;43(2):447–450. ind u ced renal recovery in heart transplant recipients in the m id term
172. Johnson WM, Bald u rsson O, Gross TJ. Dou ble jeop ard y: lu ng cancer follow -u p. Transplantation 2006;81(5):692–696.
after card iac transp lantation. Chest 1998;113(6):1720–1723. 200. Ted oriya T, et al. Reversal of chronic cyclosp orine nep hrotoxicity after
173. Cou etil JP, et al. Malignant tu m ors after heart transp lantation. J Heart heart transp lantation-potential role of m ycop henolate m ofetil. J Heart
Transplant 1990;9(6):622–626. Lung Transplant 2002;21(9):976–982.
174. Penn I, Porat G. Central nervou s system lym p hom as in organ allo- 201. Soccal PM, et al. Im p rovem ent of d ru g-ind u ced chronic renal failu re
graft recipients. Transplantation 1995;59(2):240–244. in lung transp lantation. Transplantation 1999;68(1):164–165.
175. Everly MJ, et al. Posttransp lant lym p hop roliferative d isord er. Ann 202. Starling RC, Cod y RJ. Card iac transp lant hyp ertension. Am J Cardiol
Pharmacother 2007;41(11):1850–1858. 1990;65(1):106–111.
176. Sw innen LJ, et al. Increased incid ence of lym p hop roliferative d isord er 203. Ozd ogan E, et al. Factors influ en cin g the d evelop m ent of h yp erten -
after im m u nosupp ression w ith the m onoclonal antibod y OKT3 in car- sion after heart transp lantation. J Heart Transplant 1990;9(5):
d iac-transp lant recip ients. N Engl J Med 1990;323(25):1723–1728. 548–553.
177. Arm itage JM, et al. Posttransp lant lym p hop roliferative d isease in tho- 204. Thom p son ME, et al. The contrasting effects of cyclosp orin-A and aza-
racic organ transp lant patients: ten years of cyclosporine-based thiop rine on arterial blood p ressu re and renal fu nction follow ing car-
im m u nosu p pression. J Heart Lung Transplant 1991;10(6):877–886; d is- d iac transp lantation. Int J Cardiol 1986;11(2):219–229.
cussion 886–887. 205. Scherrer U, et al. Cyclosp orine-ind u ced sym p athetic activation and
178. Ippoliti G, et al. Incidence of cancer after immunosuppressive treatment hyp ertension after heart transp lantation. N Engl J Med 1990;323(11):
for heart transplantation. Crit Rev Oncol Hematol 2005;56(1):101–113. 693–699.
179. van Geld er T, et al. Renal insu fficiency after heart transp lantation: a 206. Ong AC, et al. Effect of cyclosp orin A on end othelin synthesis by cu l-
case-control stud y. Nephrol Dial Transplant 1998;13(9):2322–2326. tu red hu m an renal cortical ep ithelial cells. Nephrol Dial Transplant
180. Lind elow B, et al. Pred ictors and evolu tion of renal fu nction d uring 9 1993;8(8):748–753.
years follow ing heart transp lantation. J Am Soc Nephrol 2000;11(5): 207. Reichensp urner H . Overview of tacrolim u s-based im m u nosu p p res-
951–957. sion after heart or lu ng transp lantation. J Heart Lung Transplant 2005;
181. Gold stein DJ, et al. Cyclosp orine-associated end -stage nephrop athy 24(2):119–130.
after card iac transp lantation: incid ence and p rogression. Transplanta- 208. Taylor DO, et al. A rand om ized , m u lticenter com p arison of tacrolim u s
tion 1997;63(5):664–668. and cyclosp orine im m u nosuppressive regim ens in card iac transplan-
182. Ojo AO, et al. Chronic renal failu re after transp lantation of a nonrenal tation: d ecreased hyp erlip id em ia and hyp ertension w ith tacrolim u s.
organ. N Engl J Med 2003;349(10):931–940. J Heart Lung Transplant 1999;18(4):336–345.
183. Boyle JM, et al. Risks and ou tcom es of acu te kid ney injury requ iring 209. Pham SM, et al. A prosp ective trial of tacrolim u s (FK 506) in clinical
d ialysis after card iac transp lantation. Am J Kidney Dis 2006;48(5): heart transp lantation: interm ed iate-term resu lts. J Thorac Cardiovasc
787–796. Surg 1996;111(4):764–772.
184. Graneru s G, Aurell M. Reference valu es for 51Cr-EDTA clearance as a 210. Brozena SC, et al. Effectiveness and safety of d iltiazem or lisinop ril in
m easure of glom eru lar filtration rate. Scand J Clin Lab Invest 1981; treatm ent of hypertension after heart transp lantation. Resu lts of a
41(6):611–616. prospective, rand om ized m ulticenter trail. J Am Coll Cardiol 1996;27(7):
185. Myers BD, et al. Cyclosp orine-associated chronic nep hrop athy. N Engl 1707–1712.
J Med 1984;311(11):699–705. 211. Ballantyne CM, et al. H yp erlip id em ia after heart transp lantation:
186. Bennett WM. Insights into chronic cyclosp orine nep hrotoxicity. Int J rep ort of a 6-year exp erience, w ith treatm ent recom m end ations. J Am
Clin Pharmacol Ther 1996;34(11):515–519. Coll Cardiol 1992;19(6):1315–1321.
212. H ilbrand s LB, et al. The effects of cyclosp orine and p red nisone on insu fficiency, and increased bone tu rnover. J Heart Lung Transplant
seru m lip id and (ap o)lip op rotein levels in renal transp lant recipients. 2005;24(6):696–702.
J Am Soc Nephrol 1995;5(12):2073–2081. 222. Klaushofer K, et al. Cyclosp orine A inhibits bone resorp tion in cu l-
213. Ku ster GM, et al. Relation of cyclosp orine blood levels to ad verse tu red neonatal m ou se calvaria. J Pharmacol Exp Ther 1987;243(2):
effects on lipop roteins. Transplantation 1994;57(10):1479–1483. 584–590.
214. H ahn H J, et al. Toxic effects of cyclosp orine on the end ocrine p ancreas 223. Au gustine SM, et al. Gastrointestinal com p lications in heart and in
of Wistar rats. Transplantation 1986;41(1):44–47. heart-lu ng transp lant p atients. J Heart Lung Transplant 1991;10(4):
215. N egri AL, et al. Osteop orosis follow ing heart transp lantation. Trans- 547–555; d iscussion 55–56.
plant Proc 1996;28(6):3321–3324. 224. Sharm a S, et al. Gastrointestinal com p lications after orthotop ic car-
216. Berguer DG, et al. Osteop orosis in heart transp lant recip ients: a longi- d iac transplantation. Eur J Cardiothorac Surg 1996;10(8):616–620.
tu d inal stud y. Transplant Proc 1994;26(5):2649–2651. 225. Steck TB, et al. Gastrointestinal com p lications and end oscop ic find -
217. Shane E, et al. Osteop orosis after card iac transp lantation. Am J Med ings in heart transp lant patients. J Heart Lung Transplant 1993;12(2):
1993;94(3):257–264. 244–251.
218. Shane E, et al. Bone loss and tu rnover after card iac transp lantation. 226. Fazel S, et al. Pred ictors of general su rgical com p lications after heart
J Clin Endocrinol Metab 1997;82(5):1497–1506. transp lantation. J Am Coll Surg 2001;193(1):52–59.
219. H end erson N K, et al. Bone m ineral loss and recovery after card iac 227. Watson CJ, et al. Early abd om inal com p lications follow ing heart and
transplantation. Lancet 1995;346(8979):905. heart-lung transp lantation. Br J Surg 1991;78(6):699–704.
220. Shane E, et al. Fractu re after card iac transp lantation: a p rospective 228. Kirklin JK, et al. Gastroin testin al com p lication s after card iac
longitu d inal stud y. J Clin Endocrinol Metab 1996;81(5):1740–1746. transp lantation. Potential benefit of early d iagnoses and p rom p t
221. Cohen A, et al. Osteop orosis in ad u lt su rvivors of ad olescent card iac su rgical interven tion. Ann Surg 1990;211(5):538–541; d iscu ssion
transp lantation m ay be related to hyp erp arathyroid ism , m ild renal 541–542.
PART
VIII
Complications of
Pediatric Surgery
CHAPTER
52
Surgical Complications in Newborns

Samir Gadepalli and Ronald B. Hirschl
■ OVERVIEW Typ ically, an u p p er GI contrast series allow s assessm ent of

the p resence, etiology, and location of a p roxim al obstru c-
Disease processes manifested by new borns are almost tion, w hereas a contrast enem a is frequ ently p erformed to
alw ays related to an underlying birth anomaly. The compli- ru le ou t obstru ction in the colon or term inal ileu m. A con-
cations associated w ith such anomalies are related to the trast enem a m ay also be p erform ed to ru le ou t a second
effects that the birth defect has upon card iopulmonary phys- colonic obstru ction d ow nstream from the prim ary anom -
iology or organ system function. For example, depending on aly that the su rgeon otherw ise m ight m iss. In ord er to m in-
the associated card iopulm onary compromise, a congenital im ize the risk of ischem ia and bow el necrosis, the w orku p
pulmonary airw ay malformation (CPAM) or congenital of bow el obstru ction in the new born shou ld be p erform ed
diaphragmatic hernia (CDH) may prove to be lethal at birth em ergently until the d iagnosis of m alrotation w ith volvu -
or manifest only in the ensuing months or years. lus has been exclud ed .
In m ost cases, the ou tcom e of new borns and infants fol-
low ing operative intervention is d etermined by the associ-
ated d irect card iop u lm onary effects, such as w ith CDH , or ■ Congenital duodenal obstruction
related to the p resence of other anom alies, especially neu - Congenital d u od enal obstru ction w ith d u od enal d ilation is
rologic or card iac d efects. Althou gh there are a few excep - d u e to atresia in 76% of cases and stenosis in 23% of cases.
tions, correction of a gastrointestinal (GI), p u lm onary, Cau ses inclu d e the p resence of a d u od enal w eb (18%),
abd om inal w all, or d iaphragm atic anom aly is straightfor- annu lar p ancreas (36%), absence of a p ortion of the d uod e-
w ard , w ith little m orbid ity and m ortality associated w ith nu m (10%), or a m alrotation w ith either volvu lu s or the
the p roced u re itself; rather, it is other associated anom alies p resence of Lad d band s (36%) (1). Annu lar p ancreas coex-
and the effect of the birth d efect up on the heart, lu ngs, or ists w ith d u od enal atresia d u e to a com m on em bryologic
nervou s system that ad versely affect outcom e. origin and is alw ays treated in the sam e m anner (2). The
p resence of a d uod enal obstru ction m ay be appreciated on
■ INTESTINAL OBSTRUCTION IN THE NEWBORN p renatal u ltrasound usually d u e to id entification of poly-
hyd ram nios (41%) or a d ilated stom ach and d uod enu m
Bilious vom iting is the hallm ark of bow el obstru ction that (d ou ble bu bble, 87%) (3). Finally, abou t half the patients
requ ires op erative intervention in the new born. N ew borns w ith d uod enal atresia are p rem atu re ( 37 w eeks gestation)
w ith bow el obstru ction shou ld have an orogastric or naso- (4); therefore, issu es related to p rem atu rity su ch as
gastric tu be placed to continuou s su ction to prevent vom it- retinop athy, intracranial bleed ing, and p u lm onary d ifficu l-
ing and p ulm onary aspiration and to d ecom p ress the GI ties m u st also be ad d ressed w hen p resent (5).
tract. Flu id resu scitation shou ld be perform ed u ntil ap p ro- Typ ical p resenting sym p tom s in the first 1 to 2 d ays of
priate u rine ou tp ut is noted (1 to 2 m L/ kg/ h). The elec- life inclu d e feed ing intolerance and em esis, w hich is u su -
trolyte statu s shou ld be evalu ated and any aberrancies ally biliou s u nless the obstru ction is p roxim al to the
corrected p rior to ad m inistration of anesthetics. The new - am p u lla of Vater, w hich is in 5% to 10% of cases. Plain
born shou ld be placed in a w arm environm ent since the abd om inal rad iograp hs d em onstrate the classic “d ou ble
su rface-to-m ass ratio of the new born is high and the ability bu bble” of an air-filled , d ilated stom ach and p roxim al
to m aintain norm otherm ia is lim ited . Rad iographic evalu a- d u od enu m in 77% of p atients (Fig. 52.1) (4). Air can be
tion typ ically begins w ith an abd om inal flat p late and u sed as a contrast agent by injecting 20 m L throu gh the
either a cross-table lateral or left lateral d ecubitu s assess- nasogastric tu be d u ring p erform ance of the rad iograp h.
ment. Fu rther rad iographic evaluation varies d ep end ing The d istal sm all intestine and colon rem ain gasless w ith a
on the sp ecific clinical picture and abnorm alities observed . d u od enal atresia. In contrast, in the setting of a d u od enal
w eb w ith an op ening or a m alrotation w ith Lad d band s or
volvu lu s, gas is often p resent in the d ow nstream GI tract.
Samir Gadepalli, Ronald B. Hirschl: University of Michigan,
The im p ortance of the d istinction is that the u rgency w ith
Ann Arbor, MI 48109.
701
702 Part VIII • Complications of Pediatric Surgery
com p lication, a sm all longitu d inal incision m ay first be

mad e along the anterolateral, d istal asp ect of the d ilated
p ortion of the d u od enu m . The anterolateral asp ect is used
in ord er to avoid the am pulla of Vater d u ring su bsequent
anastomosis. A catheter is p assed p roxim ally and d istally
to id entify the location of the obstru ction. Alternatively, a
sm all gastrotom y m ay be p erform ed and a catheter passed
d istally into the d u od enu m . Gentle p ressu re ap p lied to the
catheter at the site of obstruction m ay d emonstrate the site
of attachment of a w ind sock by the p resence of an ind enta-
tion on the su rface of the d ilated d u od enu m (Fig. 52.2). If a
sim p le w eb is p resent, the longitu d inal incision can be
extend ed across the anterolateral aspect of the w eb and the
w eb incised after id entification of the amp u lla of Vater.
Id entification of the am p u lla is best p erform ed by com -
p ressing the gallblad d er and observing the site of bile
d rainage into the d u od enu m . The ostiu m of the am pu lla of
Vater is often located at the base of or even w ithin the w eb.
In this case, excision of the w eb is ill ad vised and incision is
carefu lly perform ed after id entification of the am pu lla of
Vater in ord er to avoid inju ry to, or obstru ction of, the bil-
iary tract. Transverse closu re of the longitu d inal incision, as
in a H einike–Miku licz p ylorop lasty, effectively bypasses
the obstru ction once the w eb is p artially incised .
Alternatively, byp ass of the obstru cting lesion, w ith a
d u od enod u od enostom y, is p erform ed in 81% of cases (8). A
“d iam ond ” anastom osis betw een a transverse incision in
the p roxim al d ilated d u od enu m and a longitu d inal inci-
sion in the d istal d u od enu m is com m only u sed . The initial
exploratory d u od enal incision allow s correct placem ent of
the second incision for this anastom osis either d istal or
FIGURE 52.1. A dilated stomach and duodenum without distal gas is noted
p roxim al d ep end ing on w here the obstru ction is located
in a newborn. This is the classic “double bubble” finding in a patient with duo- (Fig. 52.2). The p roxim al incision is extend ed horizontally
denal atresia. ju st above the obstru ction and the d istal in a longitu d inal
d irection starting ju st d ow nstream from the obstru ction.
The p roxim al d u od enal incision is ap p roxim ately 1 cm in
w hich op eration is p erform ed is red u ced if m alrotation length and m aintained on the anterolateral aspect of the
w ith volvu lu s is exclu d ed as a likely d iagnosis. H ow ever, d u od enu m to avoid inju ry to the biliary tract or the p an-
in m ost cases, p rom p t su rgical intervention is ap p rop riate. creas d u ring su tu re p lacem ent. The d istal incision is also
If a classic d ou ble bu bble is observed , fu rther rad iograp hic ap p roxim ately 1 cm in length and p laced on the antim esen-
stu d y u su ally is u nnecessary. teric border. In the rare circumstance (10%) w here a wide gap
A right su praum bilical incision w ith m obilization of the exists between the ends of the duodenum, a loop of proximal
d u od enu m is typ ically used for the exploration, althou gh jeju n u m m ay be brou gh t to th e d u od enu m throu gh th e
som e su rgeons have recom m end ed a transu m bilical or mesocolon for a duodenojejunostomy.
laparoscop ic ap p roach (6,7). After a Kocher m aneu ver, the Althou gh rare, a d istal atresia is p resent in u p to 3% of
marked ly d ilated proxim al d u od enu m and the d ecom - cases; thu s, it is im p erative that the rest of the sm all bow el
pressed d istal d u od enum are id entified . If m alrotation is be exp lored . One ap p roach is to inject saline through the
present, a Lad d p roced ure is the best approach (see below ). entire bow el via a catheter placed throu gh the d uod enal
Otherw ise, m obilization of the right colon and ligam ent of incision p rior to anastom osis (4).
Treitz w ith d erotation of the sm all bow el is often help fu l to Morbid ity and m ortality for these infants are fre-
expose the entire d uod enum . qu ently d u e to com p lications from p rem atu rity, trisom y
The m ost d ifficu lt m aneu ver involves d eterm ining the 21, congenital heart d isease, and other associated anom -
site of the obstru ction becau se a “w ind sock” d eform ity alies. Feed ing is often d elayed for d ays to w eeks (m ean of
m ay be p resent su ch that the origin of the atresia or steno- 13 d ays) d u e to d u od enal d ysfu nction in the p roxim al
sis m ay be p roxim al to the change in caliber of the d u od e- d ilated d u od enu m (9). Clinicians m ay need to increase
nu m . One m u st be certain that a corrective p roced u re is feed s slow ly and to tolerate higher volu m es of feed ing
not p erform ed d istal to the actu al obstru ction. To avoid this resid u als in the new born after op eration. Som e su rgeons
Chapter 52 • Surgical Complications in Newborns 703
Proximal
Indentation
incision Distal
from NG
pushing incision
on windsock 1
“Windsock”
deformity
4
3
A B
FIGURE 52.2. A: A web that is forming a “windsock” deformity. (1) The catheter placed into a gastrotomy demonstrates the proximal
attachment of the membrane. Traction sutures are applied at this point. (2) A longitudinal incision is made and the anterior aspect of the
membrane incised/resected. The ampulla of Vater is usually at the base of the web in the medial aspect (arrow). (3) The incision is closed
transversely. B: Alternatively, a duodenoduodenostomy (diamond anastomosis) may be performed around the obstruction. (1) A trans-
verse incision is made proximally and a longitudinal incision distally. (2) The middle of the proximal incision is approximated to the proxi-
mal aspect of the distal incision. (3) A diamond shape is formed by the anastomosis, thus giving the procedure the name. (4) The
completed anastomosis is demonstrated.
su ggest that p lacem ent of a transanastom otic feed ing tu be un resp onsive to m ed ical m anagem en t that requ ires
at the tim e of correction of the d u od enal atresia allow s ear- antireflu x su rgery (N issen fu nd op lication) in 5%, d u od e-
lier initiation of feed ing, w hile others su ggest that this n al d ilation in 22%, d iminished peristalsis in 20%, delayed
m ay not be the case (10,11). Still others p erform a p lication emptying in 12%, and luminal narrow ing in 7% (9,13). Late
or resection of the red u nd ant d u od enu m at the tim e of the d uodenal dysmotility resulting in megaduod enum w ill
initial op eration (12). Rarely is reop eration requ ired in the require tapering duod enoplasty in 4% of patients (4). The
new born p eriod . Up p er GI contrast stu d ies shou ld be p er- operative (4%) and late (10%) mortality rates are due to com-
form ed only if feed ing intolerance p ersists for a nu m ber plex congenital heart anomalies (4). The overall long-term
of w eeks. Chrom osom es shou ld be assessed for trisom y survival is 86%.
21, w hich is p resen t in 21% of p atients w ith d u od enal Laparoscopic approaches to repair of d uod enal w ebs
obstru ction (9). and atresia have been d escribed w ithou t any increase in
Postop erative com p lications inclu d e anastom otic operative time, imp roved cosmesis, minimal morbid ity, and
obstruction (3%), congestive heart failure (9%), prolonged p otentially a qu icker retu rn of bow el fu nction (6,14). A
ileus (4%), pneumonia (5%), and superficial w ound infection spinal need le inserted throu gh the abd om inal w all can be
(3%) (3). Late complications includ e reoperation for ad he- u sed w ith norm al saline to d eterm ine patency of the d istal
sive obstruction in 15%, blind loop synd rome or bile reflux bow el (15). Fu rther stu d ies w ith larger nu m bers are need ed
gastritis in 22%, gastroesophageal reflux (GER) d isease to d efinitely p rove the ad vantages of this ap p roach.
Laparoscopy in neonates can be d ifficult d ue to the limited

operating space; how ever, the d ecompressed d istal bow el
in d u od enal atresia m ay allow for an easier visu alization
than most other laparoscopic proced ures. In ad d ition, the
d issection required to mobilize the d uod enum up into the
field is lim ited w ith the laparoscopic approach, thus simpli-
fying the operation.
■ Malrotation
At approxim ately 8 to 10 w eeks of d evelopm ent, the
mid gut, w hich consists of the intestines oriented on the
blood su p p ly of the su p erior m esenteric artery, rotates
270 d egrees cou nterclockw ise (from the perspective of the
surgeon looking tow ard the base of the mesentery), w hich
lead s to fixation of the proxim al sm all bow el at the ligam ent
of Treitz, attachment of the cecum and right colon in the
right low er quad rant, and broad fixation of the base of the
small-bow el mesentery to the retroperitoneum. If this rota-
tion fails to occu r, the small intestine remains on the right
sid e of the abd omen, the cecum is typically at a location
other than the right low er quad rant, and the bow el overall
remains unfixed . The entire mid gut is thus mobile and
prone to a tw ist, or volvu lu s, w hich is the form of presenta-
tion in 31% of patients but 85% of new borns (16,17). Volvu-
lu s m ay com prom ise su perior m esenteric artery inflow and
venous blood outflow, lead ing to ischemia or necrosis of the
entire sm all intestine and transverse colon (Fig. 52.3). In
ad d ition, peritoneal band s, know n as Lad d band s, that
cross over the d istal portions of the d uod enum and the
proximal jeju num are resid u e of the failed rotation and may
partially obstru ct the d u od enum and small bow el.
FIGURE 52.4. Classic upper GI with small-bowel follow-through in a patient
Eighty-nine p ercent of p atients w ith sym p tom atic m al- with malrotation. Note that the duodenojejunal junction never passes to
rotation p resent in the first year of life, w ith 50% in the first the left of the midline (spine) and the jejunum is on the right side of the
w eek and 65% in the first m onth, leaving only 11% to p res- abdomen.
ent after the first year (18). An occasional old er p atient
presents w ith interm ittent m id gu t volvulus and recu rrent One of the m ost com m on com p lications of treatm ent for
abd om inal p ain. m alrotation and acu te m id gu t volvu lu s is the failu re to rec-
ognize this entity p rom p tly, w ith ensu ing loss of the entire
m id gu t. The p rim ary symp tom of acu te m id gu t volvu lu s is
su d d en onset of biliou s vom iting (19). It is incu m bent upon
clinicians to p u rsu e the d iagnosis of m alrotation in infants
w ith biliou s vom iting. With m id gu t volvu lu s, as the d istal
bow el em p ties, the abd om en is often scap hoid rather than
d istend ed . Physical exam ination is su rp risingly u nrem ark-
able u ntil later in the p rocess w hen intestinal ischem ia and
necrosis d evelop . At that p oint, abd om inal d istension, ten-
d erness, and hem atochezia are often p resent. As the cou rse
p rogresses, hyp ovolem ia, shock, and acid osis ensu e. Con-
trast rad iograp hy evalu ation of the cou rse of the d u od e-
nu m d em onstrates that the d u od enojejunal junction
rem ains to the right of the m id line and the norm al p oste-
rior and cep halad fixation of the d u od enu m at the ligam ent
of Treitz is absent (Fig. 52.4) (20). If volvu lu s is present, a
corkscrew ap p earance of the d u od enojeju nal ju nction is
FIGURE 52.3. Malrotation with volvulus. The arrow demonstrates the site
of the volvulus. Note that the volvulus is in a clockwise direction and that the noted . Ultrasou nd is p roving to be of valu e in the d iagnosis
small bowel is ischemic. of this anom aly (21).
Mid gu t volvu lu s is one of the m ost seriou s em ergencies length of bow el su fficient for enteral nu trition trad ition-
in the neonate. Once the d iagnosis of m alrotation is m ad e ally has been consid ered to be 15 cm w ith an intact ileoce-
in the symp tom atic patient, im m ed iate laparotom y is ind i- cal valve and 40 cm w ithou t, althou gh recent d ata su ggest
cated even if rad iologic and clinical signs of volvu lu s are that it is not ju st the length, bu t also the character of the
absent. The child shou ld be rapid ly resu scitated either in bow el that d eterm ines su ccessfu l p rovision of enteral
the operating room or w hile the operating room is being feed ing (24).
read ied . Lad d p roced ure consists of the follow ing: (a) Perioperative mortality is 4% and is primarily associated
exploration of the mid gut; (b) counterclockw ise d erotation w ith sepsis from massive intestinal necrosis (17). Mortality is
of a mid gu t volvu lu s (if p resent); (c) p erform ance of a at least 50% in those with extensive ( 75%) small-bow el
Kocher m aneuver w ith d ivision of Lad d band s (w hich may infarction (20). Mortality may also be increased in those w ith
be causing the obstruction); (d ) broad ening of the m esen- congenital heart d isease (25). A recent review of patients
tery of the p roxim al jeju num and the transverse colon, w ith malrotation and heterotaxy id entified nearly 10% in-
w hich, along w ith subsequ ent ad hesion form ation, w ill hospital mortality, d ue to card iac causes, in those w ho
prevent recu rrent volvulu s; (e) retu rn of the intestine to the u nd erw ent a Lad d p roced u re, althou gh the authors note
abd om en w ithou t any tw ists in the m esentery and p lace- that the d eaths w ere not d u e to the Lad d p roced u re (26). Of
m ent of the cecu m in the left low er qu ad rant to fu rther interest, 27% of the p atients w ith heterotaxy and sym pto-
broad en the m esentery; and (f) append ectom y because of m atic m alrotation had m id gu t volvu lu s. In another stud y,
the potential of a d ifficu lt d iagnosis of append icitis in the 18% of patients w ith heterotaxy d ied after a Lad d proced ure
fu tu re w ith the inappropriate location of the app end ix (22). and 14% d eveloped postoperative small-bow el obstruction
Failure to d etorse the bow el com pletely or to lyse all Lad d requ iring an operation (27). H ow ever, all d eaths occurred
band s may result in persistent obstruction or recu rrence of m ore than 1 month after the operation and w ere d ue to the
volvu lu s. Since the volvulus is alm ost alw ays clockw ise u nd erlying card iac d isease. Therefore, the su rgeon m u st
from the su rgeon’s perspective, tw o or m ore cou nterclock- p artner w ith the card iologist in consid ering the risk benefit
w ise rotations of the bow el m ay be required , and the of a Lad d p roced u re in p atients w ith congenital heart d is-
process of d erotation can be very confu sing. One m u st con- ease and asym p tom atic m alrotation.
tinue to d erotate u ntil the entire m esentery can be broad ly Laparoscopic approaches to the Lad d proced ure, even in
follow ed to the base. the neonate, have been d escribed for m alrotation w ith and
There is no valu e in fixing—or need to fix—the intes- w ithou t mid gut volvu lu s (28–31). Case series w ith histori-
tines to the retrop eriton eu m . If com p rom ised bow el is cal controls have suggested that laparoscopic approaches
noted , a secon d look at 24 hou rs is an op tion. An other are equally safe and effective as open techniques, w ith
ap p roach m ay entail resection of clearly necrotic bow el improved cosmesis, quicker return to bow el function, and
w ith eith er rean astom osis if the statu s of the rem aining d ecreased pain (32,33).
bow el is certain or stap le closu re of the end s in areas of
com p rom ise w ith re-exp loration at 24 h ou rs. If p ossible,
su fficient length of intestine is m aintained to avoid the
■ J ejunoileal obstruction
short gu t synd rom e. Perform ance of an ileostom y is u su - Am ong cases of jeju noileal obstru ction, atresia occu rs in
ally necessary only if there is continu ed qu estion of intes- 95% w hile stenosis occu rs in 5% (8). The d iagnosis of bow el
tinal viability at re-exp loration. N ecrosis of the entire obstru ction is m ad e on the basis of fetal u ltrasound in 29%
m id gu t m akes su rvival u nlikely and excessive m orbid ity a of cases via id entification of enlarged loop s of bow el in con-
likely ou tcom e w ith requ irem ent for life-long p arenteral ju nction w ith m aternal p olyhyd ram nios, althou gh about
nu trition or sm all-bow el transplantation (23). 50% of p ositive scans are false-p ositive stu d ies (4,34).
Postop erative com plications are relatively few. Recu r- Associated in utero cau ses of jeju noileal atresia inclu d e
rence of m id gu t volvu lu s occu rs in 2% of p atients and is volvu lu s in 27%, m alrotation in 19%, gastroschisis in 17%,
thou ght to be related to a failu re to lyse all the Lad d and intu ssu scep tion in 2%. Other anom alies are unu sual
band s. Ad hesive bow el obstru ction occu rs in 1% to 10% w ith jeju noileal atresia (7%) (4). Fam ilial cau ses of intes-
of p atients and can be treated w ith nasogastric d ecom - tinal atresias have also been p ostu lated (35).
p ression, althou gh lysis of ad hesions, som etim es via a The d iagnosis can be m ad e by p lain rad iograp hy w hen
lap aroscop ic ap p roach, m ay be required . Malrotation is a large loop of d ilated , air-filled bow el is noted . The
associated w ith a d u od enal atresia or a partially obstru ct- enlarged loop s are u su ally thu m b-sized or greater on the
ing w eb in 11% of patients (18). To exclu d e this, one op tion new born rad iograp h (ru le of thu mb). If su ch large, d ilated
is to p ass a Foley catheter throu gh the d u od enu m via a loop s are noted , fu rther p reop erative d iagnostic stud ies are
sm all gastrotom y and w ithd raw it w ith the balloon gently not required except for a contrast enema, w hich often
inflated in ord er to ensu re that a d u od enal w eb or other d emonstrates a d iminu tive and u nused colon and rules out
obstru ction d oes not exist. colonic pathology, w hich can be missed d uring exploration.
In those w ith short bow el synd rom e (SBS), com p lica- Peritoneal calcification is noted in 12% of p atients, ind icat-
tions are associated w ith long-term p arenteral nu trition, ing p rior in utero p erforation and sap onification of fat from
flu id and electrolyte abnorm alities, and liver failu re. The p ancreatic enzym es in the extrud ed m econiu m .
FIGURE 52.5. Classification of

jejunoileal atresia describes the
pathology as type I (mucosal web),
type II (fibrous cord), type IIIa
(mesenteric gap defect), type IIIb
(“apple peel”), or type IV (multiple
atresias).
I II
IIIa IIIb
IV
Different typ es of jeju noileal atresia are observed (Fig. tion to the d istal bow el (36). The d eform ity is associated
52.5). Typ e I (m em branou s) occu rs in 23%, typ e II (fibrou s w ith a longer length of hosp ital stay, m u ltip le op erations,
cord ) in 27%, and typ e IIIa (m esenteric gap ) in 18%. The and d ecreased su rvival com p ared w ith other atresias (37).
“app le-p eel” or “Christm as-tree” d eform ity (typ e IIIb) Mu ltip le atresias (typ e IV) are observed in 24% of cases (4).
occurs in ap p roxim ately 10% of cases and is associated As long as rad iologic find ings exclu d e m alrotation w ith
w ith atresia near the ligam ent of Treitz, lack of a d orsal volvulus, intravenous flu id s m ay be ad m inistered , a naso-
m esentery, and p recariou s, retrograd e blood su p p ly from gastric tu be placed , and a timely, bu t not emergent, opera-
the ileocolic, m id d le colic, or right colic arterial d istribu - tion perform ed . The bow el is eviscerated and any tw ists
red uced via a sup raumbilical transverse incision. Transu m- venou s access shou ld be established before or at the tim e of
bilical approaches w ith and w ithou t laparoscopy have also op eration.
been d escribed for simple intestinal atresia w ith repair p er- Patients w ith m econiu m ileu s and all others w ith volvu-
formed follow ing evisceration through the umbilical inci- lu s and atresia shou ld have a w orkup for cystic fibrosis.
sion (38). Examination for malrotation must be d eliberate so Su ction rectal biop sy to evalu ate for H irschsp ru ng’s d is-
that this anomaly is not missed . A seromuscular biopsy of ease shou ld be p erform ed in the 9% of p atients w ith colonic
the rectum can be performed just proximal to the peritoneal atresia and those w ith volvu lu s and atresia in the term inal
reflection to evaluate for H irschsprung’s d isease. Because ileu m (40). Anastom otic leak is associated w ith jeju noileal
betw een 6% and 20% of new borns may have more than one atresia w hen it is accomp anied by H irschsp ru ng’s d isease.
atresia, a 10-French catheter is placed into the small bow el Postoperative com plications includ e ad hesive bow el
d istal to the atresia and saline gently infused until it reaches obstru ction (24%), fu nctional obstru ction at the site of the
the terminal ileum. If no contrast enema w as performed , anastom osis (9%), and the occasional anastom otic leak or
saline is infused to the rectum to rule out the presence of strictu re (4%) (4). Prolonged d ysfu nction of the proxim al
another atretic segment of bow el. The d ilated proximal seg- d ilated intestine is qu ite com m on, and d ays to w eeks m ay
ment should be resected to a reasonable caliber of bow el p ass before enteral feed s are established . Evalu ation for
( 1 cm) to prevent su bsequ ent anastomotic d ysfu nction bow el obstru ction by contrast enem a or u p p er GI contrast
since the massively d ilated proximal bow el has smooth stu d y shou ld be p erform ed after a few w eeks if feed ings
muscle hyperplasia and ineffective peristalsis. If resection are not tolerated . Typ ically, a contrast stu d y d emonstrates a
w ould compromise bow el length, an antim esenteric taper- w id ely p atent anastom osis. If the anastom osis is patent and
ing enteroplasty of the p roxim al bow el can red u ce the feed ing intolerance p ersists, a revision of the anastom osis
lu m en size. This entails resection of the m ost bulbous end of w ith resection of ad d itional bow el and / or enterop lasty to
the p roximal bow el, placement of a 20-French catheter into red u ce the p roxim al bow el caliber m ay be required . Anas-
the proximal end , and resection of the excess caliber of tom otic com p lications, su ch as a leak, m ay be ind icated by
bow el u sing a stapling d evice (8,39). The staple line shou ld p ersistent p neu m op eritoneu m or, m ore com m only, by
be reinforced w ith 5–0 Vicryl su tures to prevent a leak. d evelop m ent of a fistu la. If sep sis is p resent, operative
A d iscrepancy in caliber betw een the proximal and d is- intervention is requ ired . If not, antibiotic treatm ent and
tal bow el w ill still be present, and therefore, a proximal end p arenteral nu trition allow resolu tion of the leak and fistu la.
to d istal oblique anastomosis is performed by resecting the If a leak is p resent w ithou t fistu la or sep sis, d rain p lace-
proximal bow el at a 90-d egree angle and the d istal bow el at m ent, m ost com m only throu gh the incision or a sm all sepa-
a 45-d egree angle (Fig. 52.6). An antimesenteric incision on rate right low er qu ad rant incision, m ay be necessary.
the d istal bow el can equalize the caliber. The bow el anasto- Bacterial overgrow th is a long-term com p lication that
mosis is very similar to a vascular anastomosis and is per- m anifests as vom iting, d iarrhea, and abd om inal d istension.
formed w ith one layer of interrupted 5–0 Vicryl su tu re Bacterial overgrow th is treated w ith m etronid azole and , if
starting at the mesenteric bord er, w ith the knots on the acu te and severe, a short cou rse of broad -sp ectrum intra-
insid e of the bow el to evert the bow el ed ges. Any d iscrep- venou s antibiotics. Occasionally, resection of a d ilated seg-
ancy in size betw een the bow el end s can be ad ju sted as the m ent or enterop lasty w ill be requ ired to resolve recu rrent
anastomosis p roceed s around the antimesenteric bord er. bacterial overgrow th. Chronic blood loss from the anasto-
The closure is continued three-fourths of the w ay around , at m osis or an ad jacent u lcer can occu r m any years after the
w hich point the closure is started in the other d irection. The initial op eration. Althou gh the exact etiology is unclear,
final few su tu res placed are of the Lembert type and it is this is thou ght to be d u e to ischem ia at the anastom osis.
critical that they are not placed near the antimesenteric area Resection and revision of the anastom osis is curative,
of the bow el, as this might compromise the d istal lumen. althou gh the u lcer m ay be near bu t not at the anastom osis
In patients w ith com p rom ised blood supp ly or in the and can, therefore, be easily m issed .
setting of m econiu m ileu s or m econium peritonitis, a p ri- Short-term survival has increased in recent years to
m ary anastom osis m ay be inad visable becau se of the risk ap p roxim ately 85% to 90% (8,41). Even those w ith an
of leak. In this case, a d ouble-barrel enterostom y shou ld be ap p le-p eel d eform ity are exp ected to su rvive and , d espite
perform ed . If an apple-peel d eform ity is noted w ith tenu - early m orbid ity, w ill likely have an excellent long-term ou t-
ous blood su p p ly to the d istal bow el, an anastom osis m ay com e (42). The p eriop erative m ortality of app roxim ately
be p erform ed w hile being carefu l to avoid a tw ist in the 1% is m ainly related to associated anom alies su ch as con-
d istal bow el m esentery. Alternatively, form ing a p roxim al genital heart d isease and sep sis. The long-term causes of
enterostom y, w hile leaving the d istal bow el intact, m ay be d eath are m ainly related to the SBS observed in 25% of
the best op tion. In patients w ith gastroschisis, the thick- p atients w ith jeju noileal atresia (4). Parenteral nutrition has
ened bow el often preclu d es resection and anastom osis. In m arked ly enhanced outcome in patients w ith atresia. H ow -
this case, the bow el is red uced and the atresia ad d ressed ever, those patients w ith SBS and long-term depend ency on
app roxim ately 3 w eeks later, w hen the bow el inflam m ation parenteral nutrition may endure numerous episodes of
and thickening have resolved . Over 50% of p atients w ith catheter sepsis, probably related to translocation of enteric
jeju noileal atresia requ ire parenteral nu trition (8). Central organisms. In ad d ition, cholestasis from parenteral nutrition
FIGURE 52.6. A: For jejunoileal atresia, an end-to-back

anastomosis is performed. The distal bowel, which has the 90
smaller caliber even after resection of the bulbous proxi-
mal end, is divided on an angle to equalize the proximal
and distal bowel caliber. Often, an additional antimesen-
teric slit is required. The anastomosis is accomplished
with 5–0 Vicryl. B: An enteroplasty using a 22- or 24-French
catheter stent and staples is used for high jejunal atresia.
45
Angle distally
Antimesenteric slit
Enteroplasty
22 or 24 French dilator
B
Pathology of meconium ileus: character of contents in various parts of the bowel FIGURE 52.7. Typical intestinal
findings in the setting of meconium
ileus.
Thick fluid with
overlying gas
Microcolon
Tenacious, “tarlike”
meconium
Spheroidal, putty colored,

bile-free, hard concretions
w ith associated liver failu re is a p otentially lethal com p lica- Hypaque, or Conray may be used to perform the study; the
tion in infants that is not as prevalent in ad ults. Liver and osmolarity of the contrast agent does not appear to be of sig-
sm all bow el transp lantation have not yet had a consistent nificance. A small, unused microcolon is noted w ith thick,
im p act u p on ou tcom e in those w ith this com plication. Vita- inspissated meconium in the terminal ileum. The distal small
min d eficiencies can also occur and levels should be evalu - bowel must be filled or the therapeutic aspect of the study
ated regu larly.
Meconium
■ Meconium ileus Ileus
Meconiu m ileu s is present in approximately 20% of new -
borns w ith cystic fibrosis (43). With meconium ileu s, secre-
Complicated Uncomplicated
tion of viscous intestinal mucus, an abnormal concentrating
(atresia, perforation)
process in the proximal bow el, and imp aired pancreatic
enzym e secretion together resu lt in bow el obstruction
because of the presence of thick, tenacious meconium in the
mid -ileum and pellets of gray, inspissated m econium in the Exploratory Contrast enema (may repeat
d istal ileu m (Fig. 52.7). The hallm ark of the new born w ith laparotomy; if refluxing contrast into terminal
meconiu m ileu s is abd om inal d istention at birth, w ith m u l- evacuation of ileum, continuing to evacuate
pseudocyst; meconium, and no sepsis
tip le d ou ghy loop s of d ilated bow el noted on p alp ation.
establish bowel or severe abdominal distension)
Bilious em esis occurs and the new born fails to pass m eco- continuity or
niu m in the first 24 to 48 hours of life. Meconiu m ileu s ileostomy
is d ivid ed into u ncom p licated and com p licated . The
u ncom p licated m econiu m ileu s is sim p le obstru ction of Successful Unsuccessful
the term inal ileu m and occu rs in 55% of cases (44,45). In resolution or perforation
contrast, m econiu m -filled bow el m ay tw ist and p rod u ce a
volvu lu s, resu lting in ischem ic necrosis w ith associated
p erforation (19%) and / or atresia (48%) (46). Perforation, Low long chain Exploratory
w ith intrap eriton eal d issem ination of sterile m econ iu m , fatty acid diet, laparotomy;
m ay lead to isolated regions of calcification (m econiu m pancreatic enterotomy with
peritonitis) or even the d evelopm ent of a large m econiu m - enzyme evacuation of
containing p seu d ocyst (19%). Extra intestinal anom alies replacement meconium;
enterotomy
are u ncom m on w ith m econiu m ileu s, other than its associ- closure
ation w ith cystic fibrosis and related sequelae. or ileostomy
For uncomplicated meconium ileus, a contrast enema can
be both diagnostic and therapeutic (Fig. 52.8). Gastrografin, FIGURE 52.8. Management approach to the newborn with meconium ileus.
will not be successful. The hypertonicity of the Gastrografin (45,46,49). Dilu te 10% N-acetylcysteine is ad m inistered
likely d raw s fluid into the bowel lumen, which aids in mobi- throu gh the nasogastric tu be after resolu tion of the obstru c-
lizing the meconium. The new born undergoing such stud ies tion to p revent recu rrent insp issated secretions. Anasto-
must be kept w arm and well hydrated: typical fluid require- motic leak is u nu su al. Postop erative care is sp ecifically
ments are 150 mL/ kg/ d, and monitoring of urine output and aim ed at treatm ent of p u lm onary p roblem s w ith excellent
vital signs in an ICU is required. Adding an emulsifying p u lm onary hygiene and ad m inistration of antibiotics. Par-
agent, such as Tw een 80 or N-acetylcysteine (Mucomyst), enteral nu trition is ad m inistered u ntil enteral feed ing of a
may enhance the treatment’s effectiveness (47). Contrast p red igested , low long-chain fatty acid form u la, such as
studies are effective at relieving the obstruction in 40% to 60% Pregestim il, is tolerated . Oral p ancreatic enzym e ad m inis-
of patients with simple meconium ileus (46). Additional enetration is necessary w ith the initiation of feed ing. Closure of
mas may be performed over the ensuing days as long as the ileostomy is often accompanied by bow el d ysfunction.
progress is made refluxing contrast into the ileum, meconium One option to d etermine if the patient is read y for ostomy
is being mobilized and evacuated, and complications, such as closure is refeed ing of the ileostomy output d ow n the
perforation, w orsening abdominal distension, or sepsis, are mucus fistula. Refeed ing the d istal limb has been show n to
not encountered. Perforation w ill occur in 3% and requires be safe even in prematu re neonates, w hile d ecreasing p ar-
operative intervention with bowel resection and evacuation enteral nutrition requirements, preventing d isu se atrophy,
of the meconium (see below). and facilitating su bsequ ent reanastomosis (51).
If contrast enem as are u nsuccessful, operative interven- Long-term com p lications are related to the cystic fibro-
tion is evacu ation of the obstru cting m econiu m from the sis and its treatm ent. A sw eat chlorid e test m ay be incon-
term inal ileu m . An enterotomy in the d ilated ileu m ju st clu sive if p erform ed in the first 3 w eeks of life d ue to
proxim al to the change in lu m en caliber p rovid es access to inad equ ate sw eat p rod u ction in new borns; therefore, a
milk m econium out by external m assage and by irrigation rep eat sw eat test and confirm atory cytogenetics are u sefu l
of the bow el via an 8- to 10-French catheter w ith w arm as u p to 21% of p atients w ith m econiu m ileu s w ill not
saline, 2% to 4% N-acetylcysteine, or Gastrografin. Thick have laboratory or other clinical evid ence of cystic fibrosis
meconium is evacuated throu gh the enterotom y or flu shed (52). N ew born screening w ith im m u noreactive tryp sino-
into the colon. The ap pend ix can be rem oved and a catheter gen and cystic fibrosis transm em brane cond u ctance regu -
placed into the base of the ap p end ix to flu sh the term inal lator (CFTR) gene m utations can increase the sensitivity.
ileu m and colon. If the m econiu m cannot be su ccessfu lly Tryp sinogen, the p recu rsor to tryp sin, is elevated in
evacu ated , the bow el has been com prom ised , or an atretic p atients w ith cystic fibrosis (53).
or stenotic segment is id entified , the involved segment of Cystic fibrosis shou ld be screened for in all patients
ileu m shou ld be resected . In general, a simp le end -to-end w ith neonatal intestinal obstru ction, inclu d ing jeju nal atre-
anastom osis is p referred becau se the long-term su rgical sia, m econiu m p eritonitis, m econiu m p lu g synd rom e, and
morbid ity is low er than w ith an enterostom y (48,49). If meconiu m ileu s, thou gh the association w ith cystic fibrosis
peritonitis, bow el com promise, concern for bow el d ysfu nc- is highest and nearly u niversal w ith m econiu m ileus (54).
tion, or concu rrent m ed ical problem s m ake an anastomosis Early d iagnosis of cystic fibrosis and treatm ent u sing
risky, form ation of an ileostom y w ith an ad jacent m u cou s enzymes in patients w ith m econiu m ileu s has been show n
fistu la is an alternative, w ith plans for establishing bow el to im p rove long-term grow th and p revent m alnu trition
continu ity 4 to 6 w eeks later (45). A prim ary anastom osis (55). In m atched cohorts of p atients w ith cystic fibrosis
d ecreases the hospital length of stay and avoid s a second w ith and w ithou t m econiu m ileu s, there is no d ifference
laparotom y; how ever, nearly 31% requ ire reoperation for betw een long-term ou tcom es w ith regard to nu tritional sta-
postop erative bow el obstru ction from ad hesions and strictu s and hep atobiliary and p u lm onary fu nction, though
tu res in this p op u lation (50). there is an increased incid ence of d istal intestinal obstru c-
Atresia should be treated by resection w ith adequate tion synd rom e (DIOS) or m econiu m ileu s equ ivalent,
bowel preservation as outlined in the section on jejunoileal w hich occu rs in 9% of p atients (48,56). DIOS m ay be associ-
atresia. Before the anastomosis is performed, the distal ated w ith inad equ ate enzym e rep lacem ent or flu id intake
meconium should be evacuated as described earlier. Meco- and is u su ally su ccessfu lly m anaged w ith ad ministration
nium ascites or a meconium pseudocyst is often the result if of Gastrografin as an enem a or orally.
an in utero perforation has occurred . The goal of operations Colonic strictures, know n as cystic fibrosis (CF) fibros-
in the setting of meconium ascites or a pseudocyst is to iden- ing colonop athy, can occu r in association w ith high-d ose
tify the site of perforation and to ensure bow el continuity. In enzym e ad m inistration and requ ire operative colonic resec-
many cases, an ileostom y is required . The rind that forms the tion (57,58). Rectal prolapse can occur betw een 1 and 3 years
pseud ocyst is left on the bowel, thus avoid ing injury. In gen- of age and in general resolves w ith oral enzyme therapy or
eral, careful blunt dissection allow s separation of the loops rectal cau tery and sclerotherap y. Su bm u cosal injection of
of bow el until the entire small bow el is mobilized . hyp ertonic saline or 50% d extrose in w ater is highly effec-
Recent im provem ents in perioperative care and m an- tive in early-onset p rolap se (59,60). If rectal prolapse
agem ent of p atients w ith cystic fibrosis have resu lted in an recu rs, a second injection shou ld be consid ered and a m ilk
increase in su rvival rates to betw een 90% and 100% p rotein allergy shou ld be ru led ou t. In an old er child w ith
recu rrent p rolap se, d efinitive operative intervention can be conclud ing that H irschsprung’s d isease is the d iagnosis.
successfu l after attem pts at sclerotherapy (60). Intu ssu scep - The fu ll-thickness rectal biop sy m ay be p erform ed by
tion and gallblad d er d isease can also occu r in p atients w ith excising a p iece of rectu m u nd er d irect vision, w hich
cystic fibrosis. allow s one to ensu re that the biop sy w as taken from the
correct location and provid es a thorou gh pathologic evalu -
ation of both th e su bm u cosal and the m yenteric p lexu s.
■ Hirschsprung’s disease H ow ever, th e fu ll-thickness biop sy m u st be p erform ed in
Du ring the first 12 w eeks of fetal d evelop m ent, neu roen- the op erating room u nd er anesthesia and the resu lting
teric cells m igrate from the neu ral crest to the u p p er GI inflam m ation and scarring m ay com p licate the su bm u -
tract, from w hich they ad vance to the d istal large intes- cosal d issection requ ired for correction of H irschsp ru ng’s
tine. Failu re of m igration resu lts in H irschsp ru ng’s d is- d isease. Com p lications of rectal biop sy are exceed ingly
ease, w ith absence of ganglion cells in the su bm u cosal as rare and inclu d e p erforation and bleed ing. Whichever
w ell as the interm u scu lar p lanes of the d istal intestine, and ap p roach to biop sy is u sed , one shou ld n ot rely only on
su bm u cosal, noncholinergic, nonad renergic nerve hyp er- frozen sections to m ake th e d iagnosis of H irschsp ru ng’s
trop hy. Perhap s, as a resu lt of absence of nitric oxid e syn- d isease since th e reliability of th e frozen section is lim ited
thase, the d istal aganglionic area is in sp asm and p resents (65). Th e d iagn osis of H irschsp ru n g’s d isease m ay be
as an obstru ction to the p roxim al intestine that d ilates and especially d ifficult to m ake w hen the aganglionic segm ent
d evelop s a hyp ertrop hic m u scu laris (61). The aganglionic is “ultrashort” because the rectal biopsy and the contrast
segment is almost alw ays continuous and limited to the enema may appear normal. Anorectal manometry will, how -
descend ing or rectosigm oid region in 75% to 80% of patients; ever, d em onstrate failu re of rectal relaxation w ith d isten-
w hile long segment or total colonic d isease occurs in 15% to sion. Ultrashort segm ent H irschsp ru ng’s d isease m ay be
20% (62,63). treated with a posterior myotomy/ myectomy (POMM), as
The d iagnosis of H irschsp ru ng’s d isease m ay be d iffi- described below.
cu lt to m ake and is com m only m issed . The infant w ith con- Three op erations com p rise the m ajority of those p er-
stip ation, failu re to pass m econiu m in the first 24 hou rs of form ed in the setting of H irschsp ru ng’s d isease: the
life, failu re to thrive, vom iting, and / or abd om inal d isten- Soave, the Sw enson, and the Du ham el p roced u res (Fig.
sion shou ld be evaluated for H irschspru ng’s d isease (64). 52.9) (66,67). The intent of each is to bring the bow el w ith
Likew ise, the su rgeon should consid er H irschspru ng’s d is- ganglion cells in p roxim ity to the anu s. For the Soave p ro-
ease in the setting of any u nexplained perforation of the ced u re, the p ortion w ith aganglionosis is resected to the
d istal intestinal tract in the neonate so that the d iagnosis is p eritoneal reflection, at w hich p oint a m u cosectom y is
not m issed . Old er p atients m ay present w ith enterocolitis, p erform ed to w ithin 1 cm of the d entate line. The agan-
in w hich, d iarrhea, abd ominal d istension, vomiting, fever, glionated and ganglionated p ortion of bow el are then
and lethargy are the resu lt of stasis and intestinal ep ithelial id entified by frozen section of serom u scu lar biop sies p er-
infection. Frequ ently used d iagnostic tests inclu d e a conform ed at the p eritoneal reflection and ju st above an obvi-
trast enem a and a rectal biop sy. The contrast enem a is u sed ou s transition zone. Althou gh frozen section m ay be
to exam ine for a “transition zone” betw een the d ilated inad equ ate to d ocu m ent the absence of ganglion cells and
proxim al bow el and the narrow ed d istal colon/ rectu m . the d iagnosis of H irschsp ru ng’s d isease, it is reasonable
The transition zone, esp ecially if it is d istal, may be m issed for id entifying the p resence of ganglion cells and the sta-
if the enem a catheter balloon is inflated d uring the stud y or tu s of the p u lled -throu gh segm ent (65). H ow ever, either a
a bow el p rep aration is used . For the sam e reason, rectal nonganglionated p ortion of the bow el or a segm ent from
exams and enem as shou ld not be p erform ed in p roxim ity the transition zone m ay be u sed inap p rop riately in the
to the exam . Failu re to p ass the contrast on a repeat abd om - p u ll-throu gh if an inexp erienced p athologist is m istaken
inal rad iograp h 24 hou rs later suggests the d iagnosis of in assessing w hether ganglion cells and hyp ertrop hic
H irschsprung’s d isease. nerves are p resent. Once a ganglionated p ortion above the
Either a fu ll-thickness or a su ction rectal biop sy is the transition zone is id entified , it is then p u lled throu gh the
d efinitive m ethod for establishing the d iagnosis. A su ction cu ff and ap p roxim ated to the m u cosa ju st p roxim al to the
rectal biop sy is p erform ed app roxim ately 2 cm above the d entate line. It is critical to ensu re the p u lled -throu gh seg-
anu s and m u st be of su fficient d ep th and contain enou gh m ent is not tw isted . Postop erative enterocolitis and anas-
tissu e (ap p roxim ately three tim es as m u ch su bm u cosa as tom otic strictu re form ation m ay be higher w ith the Soave
mu cosa) to allow the pathologist to conclu d e that no gan- p roced u re than w ith the other H irschsp ru ng’s d isease
glion cells are p resent. Both the aganglionosis and the p roced u res (68).
nerve hypertrophy m u st be id entified to avoid a mistaken The Sw enson op eration involves d issection of the rec-
d iagnosis of H irschsprung’s d isease because an area of tu m to ap p roxim ately 1.5 to 2 cm from the d entate line. The
hypoganglionosis exists for approxim ately 1 cm in the anal fu ll thickness of the rectum is then everted and excised to
canal. Thus, an absence of ganglion cells may be noted if the that p oint as the ganglionated bow el is p u lled throu gh and
biop sy is p erform ed too close to the anu s, bu t the absence an anastom osis p erform ed . Care mu st be taken d uring this
of hyp ertrop hic nerves w ill p revent one from m istakenly p roced u re to d issect exactly on the su rface of the rectu m
FIGURE 52.9. The three most

common types of operations per-
formed for Hirschsprung’s disease.
The dark black lines indicate remnant
portions of aganglionated bowel. In
the Soave procedure, the aganglion-
ated bowel proximal to the anastomo-
sis has the mucosa removed.
1 cm 1 cm
Duhamel Soave (ERPT)
2 cm 1 cm
Swenson
and to m inim ize anterior d issection in ord er to avoid inju ry u sed m ay contribu te to a higher rate of com p lications (73).
to the vas d eferens and the pelvic innervation involved Even in the neonatal p eriod , p u ll-throu gh op erations can
w ith blad d er and p enile/ ejacu latory fu nction. These com - be safely p erform ed in one stage (67).
p lications are rare, although the risk of su ch problem s is Minim ally invasive ap p roaches to the Soave op eration
greater w ith this techniqu e (69,70). have becom e favored recently. A lap aroscop ic ap p roach to
Finally, d u ring the Du ham el proced u re, the aganglionic m obilization of the sigm oid colon follow ed by a p erineal
sigm oid and rectu m are resected to the peritoneal reflec- ap p roach to the m u cosectom y allow s transanal rem oval
tion. The ganglionated bow el is brou ght anterior to the of the aganglionic segm ent in continu ity w ith the rem ain-
sacru m and anastom osed to a transverse posterior rectal d er of the bow el follow ed by anastom osis of the norm al
incision p erform ed 1 to 2 cm p roxim al to the d entate line. A sigm oid colon to th e m u cosa ju st p roxim al to the d entate
GIA stapler is then placed into the anus w ith one lim b in line (74). It is now clear that lap aroscop y is not requ ired
the native rectu m and one into the pulled -through seg- for a tran sanal ap p roach in the setting of rectosigm oid
m ent. The GIA stap ler is then used to form a com m on d isease (75). Thu s, the m u cosectom y is initiated transanally
p ouch in w hich the anterior portion is the aganglionated at ap p roxim ately 1 cm above the d entate lin e and contin -
rectu m and the posterior is the ganglionated pulled - u ed u ntil the m u scu laris of the rectu m can be intu ssu s-
throu gh bow el. One m u st ascertain that the GIA stap ler has cep ted from the anu s. At that p oint, the rectosigm oid
fired correctly and that the staple line is intact w ithou t evi- m u scu laris is in cised circu m feren tially and the fu ll-thick-
d ence of bleed ing. This is a fairly sim ple op eration to p erness rectosigm oid colon m obilized by d ivid in g the blood
form . H ow ever, failu re to elim inate the septum com p letely su p p ly as it is exp osed at the anu s. A transition zone
m ay leave a d iverticu lum that can accu m ulate feces, d ilate, is u su ally visible and frozen-section biop sies are u sed
and resu lt in rectal d ysfu nction and form ation of a to confirm that the aganglionated bow el is com p letely
fecalom a. To p revent this com plication, the p roxim al p or- excised .
tion of the rectu m can be app roxim ated to the pulled - A coloanal anastom osis is then perform ed after d ivid -
throu gh segm ent, thu s elim inating the d iverticu lu m (71). ing the p osterior aspect of the rectal cuff to ensu re that the
Constip ation m ay be m ore com m on w ith the Du ham el p ro- rem aind er of the cu ff is not p rolap sed . Failu re to d o so m ay
ced ure (70). resu lt in telescop ing of the cu ff over the d istal asp ect of the
Over the last few d ecad es, pu ll-throu gh operations for p u lled -throu gh bow el w ith associated com p ression. Som e
H irschsp ru ng’s d isease have typ ically been d one in tw o su rgeons have su ggested leaving a very short cu ff to avoid
stages, w ith a p rim ary colostom y form ed follow ed by the p roblem s w ith a d ysfu nctional cu ff rem nant. In com p ari-
p ull-throu gh at 9 to 12 m onths of age. More recently, p ri- son to the longer cu ff (10 to 15 cm ) grou p , a shorter cu ff
m ary p u ll-throu gh op erations have been p erform ed w ith- ( 2 cm ), p erform ed m ore com m only on you nger and
out colostom y form ation, w ithou t an increase in sm aller p atients, w as associated w ith d ecreased hospital
intraop erative com p lication rate, althou gh the incid ence of stay, d ecreased incid ence of enterocolitis, and a d ecreased
p ostop erative enterocolitis may be increased (72). In fact, requ irem ent for d aily d ilations in a single su rgeon retro-
p roblem s w ith the stom a w hen a tw o-stage app roach is sp ective cohort stu d y (76).
One m u st also be carefu l to avoid a tw ist in the sigm oid and enterocu taneou s fistu las m ay occu r and are best
colon as it is p u lled d ow n tow ard the anus. A preop erative m anaged w ith form ation of a colostom y (84). Reop era-
contrast enem a allow s id entification of the transition zone, tive p roced u res are often requ ired in those w ith tw isting of
w hich d eterm ines the feasibility of the transanal ap p roach. the p u lled -throu gh segm ent and enterocu taneou s fistu las
In ad d ition, the contrast enem a allow s id entification of (75,85).
bow el that is d ilated to the point w here it is unreasonable The m ost com m on com p lication is enterocolitis, w hich
to pu ll the bow el through the m u scular cuff. Su ch d ilated occu rs in 20% to 50% of p atients (86,87). The etiology of
bow el m u st be id entified before the m u cosectom y has been enterocolitis is u nclear, bu t it is thou ght to resu lt from stasis
perform ed . Lap aroscopy can be used to id entify bow el and associated bacterial overgrow th. Interestingly, the inci-
w ith a caliber that w ou ld p revent p erformance of a p u ll- d ence of enterocolitis d ecreases w ith ad vancing age and is
throu gh. In that case, a colostom y shou ld be perform ed at a rarely observed p ast child hood . As m entioned previou sly,
level w ithin the ganglionated bow el as d efined by seromus- child ren typ ically p resent w ith d iarrhea, vom iting, abd om -
cular biopsy and frozen-section biopsy. Laparoscopic mobi- inal d istension, fever, and lethargy (87). Rectal examination
lization of the colon can also be used to augment a transanal d em onstrates exp losive d iarrhea, and abd om inal rad i-
operation in long-segment H irschsp ru ng’s d isease in w hich ograp h often reveals a d ilated sigm oid colon w ith a cu t-
the aganglionic segm ent extend s ou t of the rectosigm oid off sign. Rou tine p ostop erative rectal irrigation and anal
area. d ilation have been u sed for p revention of enterocolitis
Total colonic H irschsprung’s disease occurs in approxi- (88,89).
mately 10% of patients. The d iagnosis is d ifficult to ascertain The treatm ent m ay be ou tp atient w ith oral m etronid a-
because a transition zone is often not evid ent on contrast zole if the enterocolitis is m ild or inp atient w ith broad -
enema. Rectal biopsy provid es evid ence for H irschsprung’s sp ectru m intravenou s antibiotics if it is m ore severe. Rectal
disease. If initial intraoperative biopsies fail to show gan- irrigation w ith metronid azole (10 mL/ kg) w ith colonic
glion cells, an append ectomy should be performed w ith d ecompression via ad vancement of a rectal tube often helps
examination for ganglion cells w ithin the append ix in ord er to resolve this p rocess. Enterocolitis u su ally resolves w ith
to discern if total colonic H irschsprung’s disease is present. treatm ent u sing rectal w ashou ts and intravenou s antibiotics
Most often, an ileostomy is performed, although a primary for 2 to 3 d ays. The patient is then d ischarged on oral
pull-through can be consid ered . Nutritional d eficiencies, metronid azole for 2 to 4 w eeks. For recurrent enterocolitis,
failure to thrive, and fluid and electrolyte d isturbances are rectal w ashou ts or d ilatations, or both, can be performed at
common in patients w ith total colonic H irschsprung’s d is- home and ciprofloxacin can be used instead of metronid a-
ease. Sod ium repletion should be documented via measure- zole. A contrast enema should be performed to evaluate for
ment of urine sod ium. Serum bicarbonate levels should be a tw ist in the pu ll-through or evid ence of obstru ction (Fig.
assessed and replaced if necessary. Parenteral nutrition is 52.10). Any obstru ction related to the anastomosis or cuff
frequently required and associated catheter sepsis is fre- should be d ilated (90).
quent. A Martin mod ification of the Duhamel proced ure, in Althou gh a rare cau se of enterocolitis, aganglionosis of
w hich a long beveled ileorectal anastomosis is performed , the pu lled -throu gh segm ent should be evalu ated by rectal
may enhance absorption, but the incid ence of enterocolitis is biop sy (91). Persistent enterocolitis m ay be ad d ressed by
high (77). injection of botu linu m toxin (Botox) into the internal
Occasionally, extensive sm all-bow el aganglionosis is sp hincter (92). In som e cases, the ad vantages of Botox injec-
also encou ntered . With extensive sm all-bow el agangliono- tion w ill be long-lasting, w hereas in others, it w ill d em on-
sis, how ever, long-term parenteral nu trition is comm only strate benefit for 3 to 6 m onths. Reinjection of Botox is an
requ ired (70%) and m ortality is extremely high (40%) (78). op tion ; if enterocolitis p ersists, a POMM is p erform ed ,
Total intestinal aganglionosis is the severest form of w hich is successful at completely resolving symptoms in
H irschsp ru ng’s d isease, w ith an associated fam ily history 75% of patients (91). A posterior myotomy is best performed
in 15%, a RET-gene mu tation in 71%, and a m ortality of by incising the full thickness of the pulled -through segment
66%. In a m eta-analysis, long-term su rvivors existed after and the rectum for a distance proximally of approximately
intestinal or com bined liver-intestinal transplant, thou gh 8 cm starting at the dentate line followed by closure of the
the longest su rvivor w as 10 years old (79). In another mucosa. Alternatively, a posterior m yectomy may be initi-
series, all su rvivors w ere w eaned com p letely off p arental ated with a transverse incision of the mucosa at the posterior
nu trition follow ing transplantation (80). N euroenteric stem aspect of the d entate line and d evelopment of a submucosal
cell therap ies, in conju nction w ith parenteral nutrition and plane for 5 to 8 cm. The strip of full-thickness muscle extend -
su rgical m anagem ent, hold futu re prom ise in the treatm ent ing proximally is then excised and the mucosa reapproxi-
of H irschsp ru ng’s d isease (81–83). mated . Antibiotics are ad ministered . Complications from
The complications associated w ith operations performed this procedure are rare.
for Hirschsprung’s d isease are, except as noted previously, One of the m ost com m on p ostop erative p roblem s in
ind ep end ent of the typ e of operation perform ed . Rarely, p atients w ith H irschsp ru ng’s d isease is p erianal excoria-
comp lications su ch as tw isting or necrosis of the p u lled - tion (55%) (93). More com m only a p roblem in the new -
throu gh segm ent, anastom otic d isruption, cu ff abscess, born, excoriation m ay lead to severe skin breakd ow n and
Constipation/Recurrent EC post-pull-through
Contrast enema Rectal exam Rectal biopsy
Dilated colon Twisted colon Stricture Ganglia − Ganglia +
Constipation Enterocolitis
BOTOX Dilations BOTOX
No improvement No improvement No improvement
POMM, No improvement No improvement POMM

Redo pull-through
consider
ostomy
FIGURE 52.10. Flow chart for workup and treatment of patients with chronic constipation or recurrent enterocolitis
after a pull-through operation for Hirschsprung disease. Note: Botox injection may be used as a test for proceeding on to
posterior myotomy/myectomy (POMM). Should the patient derive long-term benefit from Botox, no further treatment is
needed. If the patient develops transient improvement with Botox, a POMM should be considered.
p rop hylactic treatm ent w ith p erianal barrier cream s glion cells in one p ortion of the circu m ference of the bow el
shou ld be started after op eration. Ad m inistration of H 2 d oes not m ean that ganglion cells are p resent in all areas
blockers m ay also be beneficial, w hile m etronid azole is (98). Contrast enem a shou ld also be p erform ed in the set-
u sefu l w hen reflective of low -grad e enterocolitis. Excoria- ting of severe constip ation to assess for a d ilated p roxim al
tion is m ore com m on in long-segm ent d isease (94). Post- colon or other evid ence of obstru ction or a tw isted pull-
op erative strictu res occu r in 5% to 22% of p atients and are throu gh segm ent.
m ore often observed in the new born (93,95). Rectal exam - In testin al n eu ronal d ysp lasia (IN D), in w h ich giant
ination in the first 2 to 3 w eeks w ill d eterm ine if a strictu re ganglia, ectop ic ganglia, hyp erp lasia of the su bm u cosal
is d evelop ing. The strictu re w ill often resolve over the p lexu s, and increased acetylcholin esterase activity in the
ensu ing w eeks. If not, d aily rectal d ilatation by the p ar- lam in a p rop ria are observed on biop sy, is associated w ith
ents m ay be necessary. H irschspru ng’s d isease and postoperative constipation
Most ch ild ren d o w ell p ostop eratively and have regu - (99). IN D m ay requ ire ad d itional bow el resection and red o
lar bow el m ovem ents w ithou t d ifficu lty. Constip ation is p u ll-throu gh. Reop erations for com p lications after proce-
m anaged w ith stool soften ers an d enem as. POMM is ben- d ures for H irschsprung’s d isease are necessary in a few
eficial in 90% of those w ith severe refractory constip ation p atients, u su ally d u e to refractory strictu re, recu rrent ente-
(Fig. 52.10) (96). H ow ever, POMM is rarely ben eficial in rocolitis, fistu la form ation, tw ist in the p u ll-through seg-
the setting of a retained aganglionic segm ent, w hich is ment, rectal prolapse, or retention of an aganglionic segm ent
relatively com m on am ong those w ith p ersistent, severe (85,100,101).
constip ation (91). Any of the com m on operations for H irschsprung’s d is-
Aganglionosis m ay be acqu ired d u e to ischem ia ease can be perform ed second arily. A m u cosectom y or com -
becau se the intraop erative evalu ation of the histology w as plete resection of the previou sly relocated segment can be
incorrect or the pull-through w as perform ed in a transition performed as a red o Soave p ull-throu gh (101). A Duhamel
zone in w hich ganglion cells w ere variably present along often allow s operation in a fresh plane if a Soave w as previ-
w ith hyp ertrop hic nerves. Perform ance of a pu ll-throu gh ously performed . Most patients (75% to 94%) are continent
of the bow el in the transition zone is associated w ith an follow ing a red o pull-through for H irschsprung’s d isease
increased incid ence of enterocolitis and constipation and (102). Continence is good to normal in 75% to 85% of patients
may requ ire reop erative pu ll-throu gh (97). Interestingly, after pull-through, although soiling may be observed in up to
the d istribu tion of ganglion cells m ay extend for 2 to 2.5 cm 50% (70,103–105). Finally, in cases of total colonic agangliono-
fu rther in one area than another; thus, id entification of gan- sis, a RET proto-oncogene mutation screen is need ed to rule
FIGURE 52.11. A transanal approach begins with a mucosectomy 2 cm above the dentate line (left). It is important to prevent
the cuff from telescoping within itself. Once the colon is withdrawn to the appropriate location based on biopsies, the proximal
colon is sutured to the anus (right). The posterior aspect of the rectal cuff must be divided to avoid a relative obstruction in the
future.
out med ullary thyroid d isease, and in all patients w ith d ilations and preoperative rectal irrigations (111,112). When
H irschsprung’s d isease, MEN 2 A and MTC m u tations, w ith compared w ith open pull-through proced ures, one stud y
screening and biochemical testing of susceptible family suggests that the transanal approach is nearly equivalent in
members for neuroend ocrine tumors (106). terms of long-term outcome, although the transanal proce-
A transanal ap p roach is a feasible op tion for a one-stage d ure appears to be associated w ith w orse continence scores,
pu ll throu gh if there are no associated life-threatening bu t enhancements in stooling p attern and the frequ ency of
anom alies, ongoing enterocolitis, severe proxim al bow el enterocolitis (113).
d ilation, or acu tely d eteriorating health statu s (Fig. 52.11)
(15,76). Lap aroscop y m ay or m ay not be used . If it is, serial
colonic biop sies are taken and exam ined u nd er frozen-
■ Imperforate anus
section to id entify the transition zone. The d istal colon is Im p erforate anu s occu rs becau se of an arrest of the nor-
sep arated from its m esentery u sing lap aroscop ic cau tery, m al d escent of the rectu m to the p erineu m . The d iagnosis
the p roxim al colon m obilized for the p u ll throu gh and the shou ld be ap p arent at the initial new born exam ination,
end orectal m u cosal d issection is perform ed transanally. If a althou gh a large p erineal fistu la or ectop ic anu s can easily
long-segm ent aganglionic segm ent is encou ntered , a level- be m issed . Patients are d ivid ed into those in w hom the
ing colostom y m ay be perform ed w ith a d elayed p ull end of the rectu m is above the sp hincter m u scles (high),
throu gh at a later d ate. A lap aroscopic Duham el can also be p artially throu gh the sp hincter m echanism (interm ed i-
performed laparoscopically w ith the anastomosis of the ate), or fu lly throu gh the sp hincter m echanism (low ).
proximal ganglionated bowel to the distal rectum performed From a clinical p oint of view, how ever, it is only necessary
by inserting a stapling device transanally (107). It is impor- to d istingu ish low anom alies from interm ed iate/ high
tant to confirm that no tw isting of the colon has occurred anom alies. Tw o-third s of m ales have high/ interm ed iate
w ith either p roced u re. lesions, w hereas tw o-third s of fem ales have low m alfor-
Lap aroscop ic ap p roaches offer qu icker retu rn of bow el m ations. The d istinction betw een the high/ interm ed iate
fu nction w ith oral intake begu n on the first postop erative and the low typ es is com p licated , need s to be m ad e in the
d ay, im p roved cosm esis, d ecreased postoperative p ain, first 24 hou rs of life, and affects treatm ent, since the op er-
d ecreased length of stay, w ithou t an increase in op erative ations and ap p roaches are very d ifferent. Exam ination of
tim es or read mission and enterocolitis rates (108,109). An the p erineu m often p rovid es im p ortant clu es. The follow -
alternative to the lap aroscop ic ap p roach in a neonate is a ing are all su ggestive of a low anom aly: a w ell-d evelop ed
versatile u m bilical incision, offering ad vantages of the p erineu m w ith an anal d im p le; extra skin in the m id line
lap aroscop ic ap p roach using m inim al access, w ithou t the (bu cket hand le); p resence of an anocu taneou s fistu la
need for sp ecialized equ ipm ent or skill (110). Postop erative along the p erineu m , at the p osterior vagina in a fem ale or
enterocolitis after laparoscopic approaches can occu r in u p the scrotal rap he in a m ale; or m econiu m seen throu gh a
to 66% of p atients and m ay be prevented w ith rou tine anal m em brane (Fig. 52.12). In contrast, a flat p erineu m (rocker
C B
FIGURE 52.12. A: A low imperforate anus in a male. Note the well-formed anal dimple and “bucket handle” deformity. A streak of
white meconium extending anteriorly along the scrotal raphe (arrow) indicates the presence of a low anomaly. B: Another low anomaly
with a well-developed anal dimple and meconium on the perineum extending anteriorly along the raphe. C: A high imperforate anus.
Note the lack of a fistula and the undeveloped anal dimple. Additional studies were required to establish whether this was an intermediate/
high or low anomaly, which is important since the management is distinctly different.
bottom ) w ith a p oorly d evelop ed sacru m is ind icative of a u ltrasou nd evalu ation of the p erineu m , allow ing visualiza-
high/ interm ed iate lesion. Fu rtherm ore, in both m ales and tion of a d istal rectal p ou ch and d ocu m entation of the d is-
fem ales, the absence of a p erineal fistu la or anal m em - tance betw een the anal d im p le and the rectu m . These
brane su ggests the p resence of an interm ed iate/ high techniqu es can be inaccu rate if m econiu m is im p acted in
lesion, althou gh it m ay take 24 hou rs before signs of the rectal p ou ch d u ring p elvic rad iograp hy or if the need le
m econiu m on the p erineu m ap p ear. Th e m ajority of those or u ltrasou nd p robe ind ents the anal skin d u ring asp iration
p atien ts w ith an in term ed iate/ high an om aly h ave an or u ltrasou nd evalu ation. Magnetic resonance imaging
associated fistu la to the genitou rinary tract: a rectop rosta- (MRI) p robably p rovid es the m ost accu rate inform ation
tic or rectobu lbar u rethral fistu la in the m ale and a recto- (114). If the d iagnosis of a low lesion cannot be established ,
vaginal or rectovestibu lar fistu la in the fem ale. Thu s, it is cru cial that the new born should be consid ered to have
m econiu m m ay be noted in the u rine of the m ale or com - an interm ed iate/ high anom aly.
ing from the vagina of the fem ale w ith an interm ed iate/ Over half of new borns w ith im p erforate anu s have
high anom aly. ad d itional anomalies (115). Sp ecifically, the VATERS or
Ad d itional techniqu es for ascertaining the type of VACTERL associations [having tw o or three of the follow -
lesion inclu d e (a) need le aspiration of the p erineu m to ing: V (vertebral anom alies), A (anal atresia), C (congenital
assess w hether retu rn of m econiu m is w ithin 1 cm of the heart d isease), TE (tracheoesop hageal fistu la [TEF] or
perineu m , (b) lateral p elvic rad iography after 24 hou rs of esop hageal atresia [EA]), R (reno-u rinary anom alies), and
life w ith the new born in the p rone position to assess the L (rad ial lim b d efects)] occu r in 44% of p atients (116,117).
d istance betw een the rectal pouch and the anal skin, or (c) Th e m ost sign ifican t of th ese associated an om alies are
card iac lesions that affect 21% (116). One-third have bony m ay assist w ith id entification of the d istal rectu m visu ally
sacral abnorm alities that affect blad d er and rectal innerva- or via p alp ation. Once the fistu la is ligated , the rectu m is
tion and fu nction. Occu lt sp inal d ysrap hism , consisting of m obilized by d evelop ing a su bm u cosal p lane w here the
tethered cord w ith or w ithou t associated lip om a of the rectu m abu ts the u rethra and blad d er in ord er to avoid
cord , occu rs in 14% and m ay lead to bow el or blad d er d ys- inju ry to the u rogenital stru ctu res, inclu d ing the vas d ef-
fu nction if not corrected (118). Other im p ortant associated erens and the sem inal vesicles. Once d issection has
p roblem s that shou ld be id entified to avoid long-term extend ed for ap p roxim ately 1 cm , the fu ll-thickness rec-
com plications inclu d e cryptorchid ism (19%), vesicoureteral tu m can be d issected and freed . The rectu m is ap p roxi-
reflux, and vaginal abnormalities (116,119). Workup of the m ated to the anu s as the levator ani and associated
p atien t w ith im p erforate anu s shou ld in clu d e sp ine rad i- m u scles of continence are reconstru cted in the m id line
ograp hs, a sp inal and renal u ltrasou nd , an echocard io- arou nd the rectu m . Sp ecifically, the rectu m shou ld sit in
gram , and a void ing cystou rethrogram to evalu ate for front of and above the levator ani com p lex and insid e the
vesicoureteral reflux. external sp hincter. The length of rectu m shou ld be su ch
Treatm ent of im p erforate anu s d ep end s on the level and that m od erate tension is p laced on the neoanu s so that the
typ e of lesion. If an obstru ctive anom aly is p resent, orogas- anu s cosm etically ap p ears norm al and m u cosal p rolap se
tric or nasogastric su ction shou ld be u sed to p revent asp i- d oes not occu r. The blood vessels to the d istal asp ect of
ration and intravenous antibiotics shou ld be ad m inistered . the rectu m are d ivid ed ; how ever, ligation shou ld be lim -
In general, interm ed iate/ high lesions are m anaged w ith a ited only to those requ ired for m obilization to avoid
colostomy, althou gh som e su rgeons are proponents of cor- ischem ia to the d istal rectu m .
rection in the new born p eriod either via stand ard p osterior Most low m alform ations can be d efinitively rep aired in
sagittal anorectop lasty (PSARP) in girls or via lap aroscop ic the new born p eriod . In both m ales and fem ales, an anal
rep air (120,121). A colostom y is u su ally perform ed in the mem brane may be pu nctu red and d ilated or m anaged w ith
d escend ing/ sigm oid colon, althou gh a colostom y in the an anop lasty in w hich the m embrane is incised for the d is-
new born p eriod how ever is not w ithou t risks as p rolap se tance of the external sp hincter, as id entified by electrostim -
and strictu res have been rep orted in u p to 68% of p atients u lation, and the m u cosa su tu red to the skin. A perineal
(122). The colostom y is p referably d ivid ed to p revent fecal fistu la is ad d ressed by incision of the skin and rectu m back
contam ination of the d istal loop and the u rinary tract or to the p osterior m argin of the external sp hincter, w ith
vagina. The colostom y is sew n to the fascia in tw o layers su tu re ap p roxim ation of the rectal m u cosa to the skin (cut-
to p revent p rolap se and evisceration, often w ith a skin back anop lasty). If m econiu m (often w hite) is present along
brid ge betw een the p roxim al and d istal end of the colon. the scrotal rap he, the p earls of m econiu m should be
A d istal colostogram is p erform ed after colostom y form a- u nroofed lest they increase in size and becom e infected . In
tion to ascertain the sp ecific lesion and to d ocu m ent the the fem ale, m obilization of an anterior fourchette or
p resence and location of a fistu la. The p resence of a u ri- vestibu lar fistu la requ ires p osterior transp osition of the fis-
nary-rectal fistu la in the m ale m ay lead to u rinary tract tu la to the p rop er site of the anu s. This p roced ure can be
infection. All su ch p atients shou ld be p laced on p rop hy- p erform ed by m aking a circu m ferential incision arou nd the
lactic antibiotics. fistu la accom p anied by a m id line p erineal incision (tennis
Corrective op eration by p erform ance of a PSARP is racqu et) extend ing back to the p osterior m argin of the
accom p lished at 2 to 12 m onths of life (Fig. 52.13). First, a external sp hincter as d efined by electrostim u lation. The
u rethral catheter is p laced , w hich m ay go into the rectu m m ost d ifficu lt p art of this op eration is d issection of the rec-
instead of the blad d er. If this occu rs, it can be rectified tu m from the vagina since the tw o have a com m on w all.
later d u ring the op eration. The PSARP p roced u re first Entry into the vagina is p referred to entry into the rectu m .
involves electrostim u lation and id entification of the exter- Carefu l cau tery d issection u su ally allow s sep aration of
nal sp hincter, d ivision of the p erineu m from the anterior the tw o. Com p lete sep aration m u st be p erform ed or the
bord er of the external sp hincter m u scle to the coccyx, and rectu m w ill be tethered anteriorly d u ring attem p ts to
d ivision of all m u scles of continence, inclu d ing the leva- transp ose it p osteriorly. The anop lasty is p erform ed after
tor ani, in the m id line. It is im p ortant that one stay exactly the rectu m is brou ght throu gh the external sp hincter and
in the m id line or the rectu m m ay be brou ght d ow n off to the p erineu m reconstru cted . Alternatively, the p erineu m
one sid e of the m u scle com p lex or levator ani. The rectu m m ay be left intact and sep arate incisions m ad e arou nd the
is id entified and op ened . The rectou rethral, rectovaginal, fistu la and at the site of the anop lasty (Pott anop lasty).
or rectovestibu lar fistu la is d ivid ed from w ithin the rec- The rectu m is m obilized as d escribed earlier and then
tu m and closed w ith care taken to avoid com p rom ising p u lled throu gh the anop lasty incision. The p roced u re for
the u rethral lu m en, w hich w ou ld lead to u rethral strictu re correcting an anterior fistu la in a fem ale is som ew hat
form ation. Id entification of the rectu m can be d ifficu lt, more com p lex and , therefore, is u su ally p erform ed beyond
esp ecially in the case of a blad d er fistula, w hich requ ires a 8 w eeks of age.
com bined abd om inoperineal approach; inju ry to the ure- Immediate postoperative complications include ischemia
thra can resu lt if it is not d one approp riately. Placem ent of a of the distal rectum and wound infection. Both these compli-
gastroscope w ith a light or a d ilator through the colostom y cations resolve without intervention if a colostomy is present.
Incision Electrical stimulation
Rectal pouch
C
Posterior
musculature
Closure of
Fistula levator muscles
Mobilized
D rectal
pouch F
Closure of
rectourethral
fistula
E
Skin closure
and anoplasty
G
FIGURE 52.13. The essential features of the posterior sagittal anorectoplasty used for intermediate and high malformations, which
are usually associated with rectourinary or rectovaginal fistulas. A: Electrical stimulation to identify the external sphincter location.
B: Midline incision through all posterior musculature. C: Identification of the rectal pouch and incision into the posterior, inferior wall of
the rectum. D: Identification and dissection of the rectourethral fistula from the rectum. E: Closure of the rectourethral fistula and anterior
muscle complex and mobilization of the rectal pouch. F: Closure of the posterior musculature over the rectal pouch. G: Skin closure and
anoplasty.
Femoral nerve palsy can occur due to com pression of the intermed iate or high anom alies. Blad d er continence is
fem oral nerves w ith the p atient in the prone p osition and affected as w ell. Those w ith sacral incontinence accom pa-
can be p revented by appropriate pad d ing. Postop erative nied by constip ation are m anaged w ith enem as. A Malone
urinary retention is u sually d ue to preop erative d ysfu nc- antegrad e continent enem a p roced u re m ay be an op tion to
tion, w hich is p resent in a m ajority of p atients w ith imp er- p rovid e social accep tability to p atients w ith persistent
forate anu s, even w ith a norm al sacru m, and can be treated incontinence (135). This technique u ses the append ix for
w ith interm ittent catheterization or w ith cystostom y tu be access to d eliver enemas to the colon and may be effective in
placem ent (123). Blad d er function typically im p roves w ith the constipated or incontinent patient. The artificial bow el
tim e. Antibiotic p rophylaxis shou ld be ad ministered if sphincter and electrically stimulated gracilis neosphincter
vesicou reteral reflu x is id entified or if interm ittent blad d er are tw o techniqu es that have been u sed for the treatment of
catheterization is being perform ed . A rectal d ilatation p ro- patients w ith refractory fecal incontinence w ith reasonable
gram is initiated at 2 to 3 w eeks after operation to p revent success (136). If severe incontinence persists, a permanent
strictu re form ation. It is initially perform ed by the fam ily colostomy may be a reasonable solution.
once or tw ice p er d ay until a no. 12 to 14 d ilator can be
ad vanced throu gh the neoanu s of the new born/ infant. The
frequ ency of d ilatations is sequentially d ecreased over the ■ THORACIC ANOMALIES
ensu ing 6 m onths. Colostom y closure is p erform ed only
after the neoanu s has been d ilated to the size ind icated ear-
■ Congenital pulmonary airway malformation
lier. Occasionally, an anal stricture forms d espite a d ilata- CPAM consists of an arrest of airw ay d evelop m ent su ch
tion p rogram . An anop lasty w ith posterior d ivision of the that large cysts (m acrocystic) or sm all cysts (m icrocystic)
strictu re and ap p roxim ation of the m u cosa to the skin can are form ed (137,138). The anomalies are often id entified in
then be p erform ed if n ecessary. Alternatively, skin flap s utero and m ay sp ontaneou sly d ecrease in size or even d is-
can be p laced into the sites of strictu re incision in ord er to ap p ear p rior to d elivery (139,140). In a m inority of patients,
p revent recu rren ce (124). Rectal m u cosal p rolap se is the CPAM com presses the ad jacent lung and esophagus,
m anaged by excision of th e red u n d ant m u cosa. An aton ic resulting in polyhyd ram nios and physiologic com prom ise
m egarectu m can resu lt after PSARP an d requ ire resection both in utero and after birth—in utero this m ay m anifest
by end orectal p u ll-throu gh (125,126). If the rectu m is itself throu gh d evelop m ent of non im m u n e hyd rop s,
large at the tim e of initial PSARP, tap ering m ay be ind i- w h ich is associated w ith a h igh m ortality rate (141). Id en-
cated to attem p t to prevent this com plication. Recu rrent tification of in utero h yd rop s in a p atient w ith CPAM is an
rectou rethral fistulas occu r, though rarely, and can requ ire ind ication for d elivery or, if lu ng m atu rity w ill not allow
red o PSARP, w hich is successful at enhancing continence in d elivery, fetal intervention, w hich m ay entail asp iration
most cases (127,128). Likew ise, a red o PSARP m ay be of of a m ajor cyst, cyst-am n iotic flu id shu nt p lacem ent, or
benefit in p atients in w hom MRI evalu ation of p lacem ent lu ng lobe resection (142–144). Follow ing birth, resection
of the rectu m w ithin the levator and sp hincter m u scles of th e in volved lu n g is ind icated in n ew born s w h o are
d em onstrates an inappropriately placed anu s and rectu m sym p tom atic (139). Intu bation and ventilation shou ld be
(129). u nd ertaken w ith care and only w hen necessary since over-
The postoperative mortality should be 5% for low exp ansion of the involved lobe(s) m ay occu r. Extracorpo-
imperforate anus and 15% for the high/ intermediate variety real life su p p ort (ECLS) or extracorp oreal m em brane
and is usually the result of associated anomalies (130). oxygenation (ECMO) m ay be necessary if gas exchange is
Patients should be follow ed carefully for evidence of geni- com p rom ised either p reop eratively or p ostop eratively d u e
tourinary problems. Evaluation for sacral anomalies and to lung com pression or the d evelopm ent of pu lm onary
presence of a tethered spinal cord should be performed. hyp ertension (145).
New borns w ith low malformations have an excellent out- N o intervention is recom m end ed at birth in asym pto-
look, with fecal continence documented in 50% to 75% of m atic new borns, w hich form the m ajority (146). CPAMs d o
patients and normal anorectal function in 52% (126,131,132). not regress after birth. Becau se of the p otential for infection
The remaind er of the patients have occasional accid ents or an d the d evelop m ent of rhabd om yosarcom a and other
soiling and fair to norm al continence. Constipation may, m alignancies d u rin g child hood , m ost su rgeons recom -
how ever, be a problem in 25% and vaginal abnormalities m end excision at 3 to 12 m onths of age (147,148). Dop pler
and scarring may be an issue that often requires operative u ltrasound or CT im aging w ith contrast optim ally is p er-
intervention in a substantial number of patients (133). form ed p reop eratively to evalu ate for an aberrant system ic
Ap p roximately 80% of p atients w ith high/ interm ed iate artery, w hich is seen in a p u lm onary sequ estration. CPAMs
anom alies have reasonable resu lts, w ith occasional soiling are often sim ilar in p resentation to a sequ estered lobe,
noted in som e of these patients (126,134). The rem aining althou gh the latter is alm ost alw ays in the low er lobe. Asso-
patients have fair to poor results, w ith varying d egrees of ciated anomalies, inclu d ing renal agenesis or d ysgenesis,
continence. The fu nctional resu lts are m ostly related to the d iap hragm atic hernia, im p erforate anu s, intestinal atresia,
presence of sp hincter m u scle hypop lasia and the abnorm al or congenital heart d isease, occu r in 20% of cases. In the
sacral innervation that m ay be observed in p atients w ith absence of hyd rop s, m ortality shou ld be m inim al (143).
Stand ard lobe resection is via thoracotom y, althou gh a

nu m ber of su rgeons are p rop onents of a thoracoscop ic
approach (149,150). If the lesion is in m ore than one lobe
(14%), segm ental resection or nonanatom ical resection
w ith a stap ling d evice is perform ed . Pneu monectomy is
sp ecifically avoid ed becau se of the risk of m ed iastinal shift
and com p rom ise of ventilation in new borns and infants.
When a p neu m onectom y is necessary, the hem ithorax
shou ld be filled w ith p lastic balls or an exp and er to avoid
su ch com p lications. An expand able prosthesis can be con-
tinuously inflated to counteract the m ed iastinal shift as the
child continu es to grow (151–153). Op erative resection of
the involved lobe is und ertaken w ith care to id entify an
aberrant arterial vessel in case one is present, w hich u su -
ally is observed entering the thorax through the inferior
pu lm onary ligam ent. Incid ental d ivision of this vessel
w ithou t control and ligation m ay lead to retraction of the
vessel below the d iap hragm and m assive bleed ing. Persis-
tent air leak is u sually lim ited to those u nd ergoing segm en-
tal resection and w ill m ost often resolve w ith chest tu be
su ction over a p eriod of d ays to w eeks. Alternatively, p lace-
m ent of a thoracoscop e throu gh the chest tu be site w ith
injection of fibrin glu e at the site of the air leak m ay lead to
resolu tion. Placem ent of fibrin glu e over the raw surface of
the lu ng at the tim e of segm ental resection can prim arily
prevent air leak.
FIGURE 52.14. Angiogram demonstrating a left pulmonary sequestration
with a large aortic systemic arterial blood supply extending from below the
■ Pulmonary sequestration diaphragm. Failure to control this vessel during resection of the sequestration
may result in potentially exsanguinating hemorrhage as the vessel retracts
Pu lm onary sequ estrations d erive their arterial blood su p - below the diaphragm.
ply from the systemic arterial circulation, usually via one or
more large arteries that extend from below the d iaphragm
and enter the thorax throu gh the inferior p u lm onary liga- and hem othorax (154). The p ersistent air leak w ill usually
ment (Fig. 52.14). The sequ estered lobe can be either resolve w ith thoracostom y su ction. If the leak d oes not
intralobar (73%) or extralobar (27%). Sequ estrations of the resolve, then thoracoscop y w ith ap p lication of fibrin glu e
intralobar variety are incorporated into the su rround ing to the site of the air leak shou ld be p erform ed .
lung and often have a norm al venou s d rainage (154). In
contrast, extralobar sequ estrations are sep arate from the
norm al lu ng, have a separate pleu ral covering, and d rain
■ Foregut duplication cyst
blood into the azygou s veins (155). Sequestrations are m ore The lu ngs and the esop hagu s d evelop from the foregu t. It
com m only fou nd in or ad jacent to the low er lobe (154). is som etim es d ifficu lt to d istingu ish betw een d evelop -
Arteriovenou s fistulas w ith hem optysis or high-ou tput m ental cysts that are p u lm onary (bronchogenic cysts) and
heart failu re m ay occu r. N either variety typically has com - esop hageal (esop hageal d u p lication cysts) in origin. In
mu nication w ith the airw ay, although the intralobar fact, 71% of intram u ral esop hageal cysts contain resp ira-
sequ estrations m ay be aerated from the su rrou nd ing lu ng. tory ep itheliu m (158). Foregu t d u p lication cysts are lined
Intralobar sequ estrations are frequ ently associated w ith by resp iratory or GI ep itheliu m , and both have been
recu rrent infections in the lobe and require excision, u su - noted in a single cyst (159). Ap p roxim ately 25% of patients
ally via lobectom y. Extralobar sequestrations are excised p resent d u e to incid ental cysts d etected on chest rad i-
for d iagnosis w ithou t lung resection. It is critical to id entify ograp h in asym p tom atic in d ivid u als (160). Otherw ise,
and ligate the large arteries in the inferior p u lm onary liga- cysts are id entified if they p rod u ce cou gh, d ysp nea, recu r-
ment or extend ing d irectly from the aorta, w hich uniform ly rent p neu m onia, hem op tysis, or d ysp hagia or if the cyst
accomp any these lesions, as failu re to recognize such ves- becom es infected (161). Su ch cysts can comp ress the tra-
sels m ay resu lt in d isru p tion and exsangu ination as the ch eobron ch ial tree and create life-th reatenin g airw ay
vessel(s) retract beneath the d iaphragm (156). Rarely, the obstru ction, esp ecially in new borns and infants and in the
sequ estration can cau se com p ression of the ad jacent lu ng su bcarinal location (160,162–164). Therefore, in the sym p -
w ith d evelop m ent of respiratory insu fficiency (157). Op er- tom atic new born, the cysts sh ou ld be ad d ressed op era-
ative com p lications are rare and inclu d e p ersistent air leak tively. Intrap u lm onary cysts m ay be m istaken for a lu ng
abscess if air-flu id levels are present from an airw ay com - born in a 30-d egree to 45-d egree u p right position w ill
mu nication. Intrapu lm onary cysts are excised via lobec- inhibit reflu x of GI contents into the tracheobronchial
tom y (160). Med iastinal cysts can be large and d au nting to tree. In travenou s antibiotics shou ld be ad m inistered p ro-
the su rgeon, bu t a plane of d issection is usually fou nd that p h ylactically if the p atient exhibits signs of p n eu m onia.
allow s relatively easy resection. Foregu t d uplication cysts Mech an ical ventilation should be performed only if neces-
may be intim ately involved w ith the esophagu s, bu t they sary because of the risk of gastric perforation w hen a TEF is
rarely com mu nicate w ith the esop hageal lu m en and typ i- present (167). Gastric perforation is often associated with the
cally can be d issected from the mu scu laris of the esophagu s sud d en d evelopment of abd ominal d istension and respira-
leaving the m u cosa intact. Thu s, esop hageal resection tory compromise. Management of the perforation includ es
shou ld rarely be requ ired . Occasionally, they may comm u - need le paracentesis of the abd omen en route to surgery,
nicate w ith the trachea or tracheobronchial tree. Short-term w here the low er esophagus is occlud ed w ith a catheter intro-
com plications inclu d e air leak if there is com m unication d uced through the perforation, after w hich a thoracotomy
w ith the tracheobronchial tree and recu rrence if the cyst is w ith d ivision of the fistula, creation of an esophageal anasto-
not completely resected (158,165). Long-term comp lications mosis if appropriate, and repair of the gastric perforation are
are rare. in order.
Air in the abdomen on radiograph suggests the presence
of a d istal TEF (85%), and conversely, its absence indicates a
■ Esophageal atresia and pure EA (7%) (Fig. 52.15). Rad iologic evaluation, performed
tracheoesophageal fistula w ith careful ad ministration of contrast med ium into the
Patients w ith EA frequ ently have an in utero history of upper pouch with the patient sitting upright to avoid aspira-
polyhyd ram nios and a sm all or absent stom ach on u ltra- tion, w ill verify the d iagnosis of EA and prevent a proxim al
sou nd (166). After birth, d ifficu lty w ith hand ling secretions TEF from being missed . A p roximal fistu la is present in
is often accom panied by choking and cou ghing w ith feed - approximately 1% of patients and may be missed at the time
ing. Usu ally an u nsu ccessful attem pt is m ad e at p assing a of operation because the fistula may be proxim al and high
nasogastric or orogastric tube. Cu rling of the tu be in the up in the thorax at a level above rou tine d issection (Fig.
d ilated p roxim al esop hageal p ouch is pathognom onic for 52.16). Proximal fistu las are often associated w ith smaller
EA. If not recognized and controlled by proxim al p ou ch caliber and shorter proximal pouches (extend ing at most
placem ent of a Replogle tu be, w hich has perforations only d ow n to the T1 vertebra) because of the in utero d ecompres-
near the end of the tu be, aspiration of oral secretions may sion of the p roxim al pou ch that the fistu la provid es. The
occu r. In ad d ition, gastric secretions m ay reflu x u p throu gh presence of a sm all p roxim al p ou ch su ggests that the anas-
a TEF, if p resent, and lead to fu rther lung contam ination tom osis w ill be u nd er consid erable tension. Bronchoscop y
and the d evelop m ent of pneu monia. Maintaining the new - m ay be p erform ed to id entify a p roxim al fistu la in th e
FIGURE 52.15. The three most

common forms of esophageal atre-
sia and tracheoesophageal fistula.
(A) constitutes 85% of the total,
while (B) and (C) together make up
another 10%. The rarer types are
not depicted.
Proximal Proximal Proximal

esophageal esophageal tracheoesophageal
atresia atresia fistula without
esophageal
Distal atresia
tracheoesophageal
fistula
Distal
esophageal
pouch
A B C
Since 64% of p atients have associated anom alies, a

search for congenital d efects shou ld be u nd ertaken (169).
Ap p roxim ately 15% of p atients w ith EA and TEF have a
constellation of find ings com patible w ith the VATER or
VACTERL association (vertebral d efects, anal atresia, car-
d iac anom alies, TEF and EA, renal d efects, and lim b abnor-
m alities). The m ost com m on anom alies are card iac (38%)
and are resp onsible for m any of the d eaths associated w ith
EA and TEF. Renal anom alies (17%) shou ld also be id enti-
fied so that fu rther d am age is not incu rred (170).
In general, p atients w ith EA and a d istal TEF have ad e-
qu ate esop hageal length to allow p rim ary reconstru ction.
Thu s, a rep air is u nd ertaken w ithin the first 24 to 48 hou rs
u nless contraind icated by p rem atu rity, the p resence of
congenital heart d isease, or another p hysiologically com -
p rom ising situ ation. In that case, tem p orizing w ith p roxi-
m al p ou ch Rep logle su ction and a gastrostom y tu be w ith
p lans for d elayed rep air m ay be the best strategy. Other-
A B w ise, an ap p roach throu gh the right chest u sing a m u scle-
sp aring incision is p erform ed w ith access via the fou rth
FIGURE 52.16. A: Three-dimensional CT reconstruction of the trachea and intercostal sp ace. The p resence of a right aortic arch,
esophagus. White arrow on proximal tracheoesophageal fistula, which was fou nd in 2% of p atients w ith the EA/ TEF anom aly, shou ld
missed at the initial operation; black arrow on remnant pouch. B: Similar
reconstruction from different rotational angle depicts accessory bronchus be id entified on echocard iograp hy so that a left thoracic
(arrow). (From Islam S, Cavanaugh E, Honeke R, et al. Diagnosis of a proximal ap p roach can be u sed (171). An astom osis via a right th o-
tracheoesophageal fistula using three-dimensional CT scan: a case report. racotom y in the p resence of a right aortic arch is associ-
J Pediatr Surg 2004;39(1):100–102, with permission.)
ated w ith a high anastom otic leak rate (42%) and often
requ ires a left thoracotom y for com p letion of the op eration
op erating room prior to repair of the EA/ TEF (168). H ow - (172). A d ou ble aortic arch m akes d ivision of the TEF and
ever, bronchoscopy may miss small proximal fistulas, and esop hagoesop hagostom y d ifficu lt via either ap p roach. The
contrast stud y of the proximal pouch appears to be an d istal TEF is id entified in the region of the carina and is
equally useful adjunctive test, w hen appropriately per- d ivid ed (Fig. 52.17). Prior to d ivision of the fistu la, m ainte-
form ed , though the risks of aspiration must be w eighed . nance of oxygenation m ay be tenuous and requires that the
FIGURE 52.17. Repair of esopha-

geal atresia (EA) and tracheoe-
sophageal fistula (TEF) A: The TEF
has been divided and the tracheal
opening closed with 5–0 or 6–0 PDS
suture. B: The feasibility of primary
anastomosis between the two
esophageal segments is being
assessed. C: A circumferential prox-
imal esophagomyotomy is being used
to gain additional length.
Esophageal
myotomy
C
A
su rgeon interm ittently allow exp ansion of the right lu ng; 3 months p rior to an attem p t at a p rim ary repair (176). At
this p roblem u su ally resolves once the fistu la is ligated . A tim es, the fistu la m ay need to be ligated if respiratory
few m illim eters of esophageal tissu e are left on the trachea effects of p u lm onary soilage are observed . Daily d ilation of
d u ring d ivision of the TEF in ord er to avoid com prom ise of the p roxim al p ou ch m ay enhance lengthening. Another
the tracheal lu m en. In contrast, leaving too m uch esop ha- op tion is to m obilize the entire d istal and p roxim al esop ha-
gus on the trachea can com prom ise the length of the d istal gu s, to p erform the anastom osis u nd er consid erable ten-
esophageal segm ent and result in an airw ay d iverticulu m , sion, and to m aintain the p atient sed ated w ith the head in
w hich can serve as a sou rce of ongoing airw ay contam ina- the flexed p osition to d ecrease p ostop erative anastom otic
tion. The tracheal closure is checked for an air leak w hile tension (177). Alternatively, a p roxim al or d istal pouch cir-
und er saline w ith application of sustained airw ay p ressu re. cu lar m yotom y of Livad itis m ay be p erform ed , w hich
The d istal esop hagu s can be m obilized w ith little fear of it increases the length by 1 to 2 cm (Fig. 52.16) (178,179). With
being d evascu larized . The p roxim al esophageal p ou ch is this techniqu e, the m u scu laris is d ivid ed circu m ferentially
best id entified by having the anesthesiologist ad vance a w hile the m u cosa is carefu lly m aintained intact. Tw o or
catheter p laced through the m ou th into the pouch. A su tu re three p roxim al m yotom ies m ay be u sed to enhance length.
is placed in the ap ex of the p roxim al pouch for m anipu la- Unfortu nately, com p lications su ch as leaks, strictu re, out-
tion in ord er to avoid trau m a d u e to rep eated grasp ing of p ou ching of the esop hagu s at the site of the m yotomy, and
the tissu e. The pou ch is m obilized in the u pp er m ed i- esophageal d ysfu nction are associated w ith this techniqu e
astinu m ; care is taken w hile m obilizing the anterior esop h- (180). A sp iral m yotom y m ay be u sed to d ecrease the ou t-
agu s becau se of the risk of entry into the m embranou s p ou ching associated w ith m yotom y. All these situ ations
trachea. Use of cautery shou ld be lim ited , esp ecially in the p resent a challenge to the su rgeon w here a d ecision m u st
ap ex of the thorax, becau se of the risk of therm al inju ry to be m ad e on w hether to attem p t to salvage the native
the recu rrent laryngeal nerve. An esophagoesop hagostom y esop hagu s. In p atients w ith very long gap s (greater than
is perform ed in m ost cases u nd er m ild to m od erate levels six vertebral bod ies), rep lacem ent of the esop hagu s w ith a
of tension. Care m u st be taken to ensure that su tu res natu ral cond u it m ight be the best op tion (175).
includ e the full thickness of the esophagus since the Other innovative techniques for lengthening the esopha-
mu cosa can easily retract. A nasogastric tu be is p assed gus w hen the proximal and d istal segments cannot be
throu gh the anastom osis into the stom ach to ensu re brou ght together inclu d e a mu ltistaged approach in w hich
patency of the d istal esophagu s. Gastrostom y tu bes are an esophagostomy is formed on the chest and sequ entially
d one only if the presence of other anom alies suggests that lengthened every 2 to 3 w eeks by ad vancing the esophagos-
tu be feed ing w ill be required . Most su rgeons u se a retro- tomy inferiorly along the chest w all (181). This technique
pleu ral ap p roach and place a d rainage tu be near, bu t not allow s sham feed ings, w hich are important for normal feed -
on, the anastom osis at the end of the op eration to contain a ing d evelopm ent, to take place. Another app roach p ro-
postop erative anastom otic leak, w hich occurs in 16% of moted by Scharli involves transverse d ivision of the lesser
cases (169). Sm all openings in the pleura are unim p ortant curvatu re of the stomach along w ith ligation of the left gas-
and shou ld not be closed w hen a retrop leu ral ap p roach is tric artery (182). Similar to a Collis proced ure, except per-
used . Silk su tu res are associated w ith a tw o- to three-fold formed along the lesser curvature, the technique is effective
increase in the incid ence of anastom otic leak (173). A leak, at lengthening the d istal esop hagus (183).
along w ith tension and GER, can resu lt in postop erative Foker et al. have su ggested p lacing externalized sutu res
strictu res, fou nd in u p to 40% of cases (174). Orop haryn- on the end s of the esop hagu s to ap p ly tension w ith even-
geal su ctioning is lim ited to 6 cm from the lips in ord er to tu al ap p roxim ation of the end s (184). With this approach,
avoid trau m a to the anastom osis. An esop hageal contrast continu ou s traction is u sed to slow ly approximate the end s
stu d y is p erform ed approximately 1 w eek after op eration. of the esop hagu s follow ed by p erform ance of an anastom o-
If the anastom osis ap pears intact, feed ings are initiated , sis. Postop erative strictu res and reflu x m ay occur w ith this
antibiotics are d iscontinued , and the retrop leu ral chest ap p roach and can be m anaged w ith d ilations and Thal fun-
tu be is rem oved . d op lication, resp ectively (185). At tim es, the sutures m ay
In p atients w ith isolated EA w ithou t a TEF (p u re EA), p u ll throu gh the end s of the esop hagu s w ith p otential leak
the d istal esop hagu s is typ ically short (ap p roxim ately tw o from the end s of the esop hagu s. Op tions w hen this com pli-
vertebral bod ies), w hich preclud es im m ed iate rep air. Som e cation occurs are to replace the su tu res w ith repair of the
patients w ith EA and a d istal TEF w ill have a longer gap leak (if present) or to convert to a cervical esop hagostom y
betw een the p roxim al and d istal esop hagus (m ore than tw o w ith p lans for esop hageal reconstru ction at a later d ate.
vertebral bod ies). Som e of the latter situ ations can still be Finally, an intrigu ing ap p roach d evelop ed by Gough
rep aired via a p rim ary app roach. Patients w ith p u re EA or (186) su ggests formation of a flap from the d ilated proximal
those w ith long-gap atresias that are not am enable to a p ri- fistu la, w hich is then tu bu larized in ord er to enhance prox-
mary ap p roach can still be repaired at 8 to 12 w eeks w ith a im al esop hageal length. Whatever ap p roach is used , a long
d elayed p rim ary anastom osis (175). The m anagem ent gap ad versely affects the outcom e w ith regard to d eath
involves placem ent of a gastrostom y tu be and allow ing for (18%), anastom otic leak (31%), strictu re (44%), and GER
grow th of the p roxim al and d istal pou ch over the ensu ing (56%) (187).
In general, all attempts are m ad e at salvaging the native occu rs in 10% of p atients w ith isolated EA, and the lack of
esop hagu s (188). H ow ever, w h en the esop h agu s cann ot air in the GI tract can d elay d iagnosis of the d u od enal atre-
be approximated or if complications of stricture, recurrent sia u ntil a gastrostom y tu be is p laced . An intraoperative
GER, or esophageal dysfunction persist, esophageal replace- contrast stu d y at the tim e of gastrostom y tu be p lacem ent
m ent is an alternative. Right or left colon, jejunum , or the help s to id entify this com bined anom aly (176). Im p erforate
stom ach, either as a reversed gastric tu be or as a gastric anu s shou ld be ad d ressed by p erform ing a colostom y
transp osition, can be u sed (189–193). Although an effective u nless a p rim ary, lap aroscop ic rep air of the im perforate
solu tion to establishing esop hageal continu ity, the com - anu s is to be p erform ed .
p lication rate w ith esop hageal rep lacem ent is su bstantial Patients w ith a TEF bu t no EA (4%) often have episod es
and inclu d es an anastom otic leak rate of ap p roxim ately of gastric d istention d u ring crying and choking, recurrent
30%, strictu re form ation in 20% to 60%, and a m ortality of p neu m onia, and cyanotic sp ells d u ring feed ing. The d iag-
5% (189–191,194,195). Anastom otic leaks alm ost alw ays nosis is best m ad e by a contrast sw allow, bronchoscopy, or
resolve sp ontaneou sly. When a colon cond u it is u sed , it esop hagoscop y, w hich m ay d em onstrate the H -typ e fistula
can be p laced behind the hilu m of the lu ng on either sid e betw een the trachea and esop hagu s. A Fogarty catheter
or in a su bsternal p osition, althou gh the latter is associ- m ay be p laced throu gh the fistu la at the tim e of bron-
ated w ith a higher stenosis rate (189). A vagotom y is effec- choscop y to help w ith id entification of the fistu la at op era-
tive in p reventing the d evelop m ent of u lcers w hen a colon tion. Ligation of the fistu la is u su ally p erform ed via a right
cond u it is u sed . The colon m ay becom e red u nd ant in the cervical ap p roach. The recu rrent laryngeal nerve m ust be
chest, lead ing to d ysfu nction and stasis (16%). Reop era- id entified to p revent inju ry, the most com m on com plica-
tion is necessary in ap p roxim ately 50% of p atients and is tion of this p roced u re. Recu rrence of the fistu la is rare.
m ost often p erform ed to red o the esop hagocolic or colo- Overall su rvival rate is 95% (169). Mortality is u su ally
gastric anastom oses d u e to strictu res (194,196). Gastro- second ary to associated anom alies and is associated w ith
colic reflu x m ay also occu r, and ap p roxim ately 20% w ill the presence of m ajor card iac d isease and birth w eight
u ltim ately requ ire rep lacem ent of the colon graft, w hich is 1,500 g (Table 52.1) (198). One of the m ost d ifficult d eci-
best m anaged by p erform ance of a gastric transp osition or sion-m aking situations involves the prem atu re new born
a free jeju nal graft (194,196). w ith resp iratory d istress synd rom e and EA/ TEF since the
Another option for esophageal replacement is the associated ventilator leak throu gh the fistu la increases w ith
reverse gastric tu be, w hich is form ed by creating a tu be airw ay p ressu re escalation; therefore, ligation of the fistula
from the greater cu rvatu re of the stom ach. This is m ost is id eally p erform ed before com p rom ised resp iratory sta-
often brou ght u p to the neck throu gh w hat w ou ld have tu s p reclu d es a safe op eration, requ iring close monitoring.
been the esop hageal bed . Com p lications are sim ilar to Early thoracotom y and ligation of the fistu la p rovid es an
those of the colonic su bstitu tes w ith the ad d ition of leak ability to ventilate and p revents gastric d istension thou gh
from the long su tu re line. In ad d ition, com prom ise of the this d ecision m u st w eighed against the overall clinical sta-
stomach size in new borns m ay be a p roblem . Finally, gas- tu s of the neonate (199).
tric transp osition is a successful op tion since the blood su p- Im m ed iate p ostop erative com p lications inclu d e sm all
ply to the stom ach is excellent and the operation is anastom otic leaks on p ostop erative contrast stu d y in 15%
technically easier than other alternatives. This option can of EA/ TEF p atients w ith p rim ary rep air. Alm ost all sm all
be u sed even w hen previou s op erations have been per- leaks w ill resolve sp ontaneou sly w ith continu ation of IV
formed on the stom ach (193). The right and left gastroep i- antibiotics and chest tu be d rainage. A rep eat stu d y is per-
ploic arteries are m aintained intact w hile the stom ach is formed 1 w eek later, and oral feed ings are held u ntil the
otherw ise m obilized . The d istal esop hageal segm ent is leak resolves. Disru p tion of the anastom osis occu rs in
excised and the fund us preferably brou ght through the ap p roxim ately 5% d u e to excess tension, ischem ia, or poor
posterior m ed iastinu m , w hich lim its the potential com p li- surgical techniqu e and presents w ith persistent pneum oth-
cation of gastric d isten sion. Th e p osterior asp ect of the orax, resp iratory d istress, p leu ral flu id , and / or sepsis. The
stom ach m u st be anchored to the sternocleid om astoid
m u scles in the infant and to the p revertebral fascia in the
old er p atient to p revent retraction of the stom ach into the Table 5 2 .1 Pr ed ict or s of su r viva l from a n
thorax. A p ylorom yotom y should be perform ed to enhance esop h a gea l a t r esia a n om a ly
gastric em p tying. The d um ping synd rom e occu rs in a
Survival
m inority of p atients in the p ostop erative p eriod bu t typ i-
Group Total (n) Dead (n) Rate (%)
cally resolves over the first year. Care m u st be taken to
avoid a tw ist in any of the cond u its perform ed , w hich m ay I. Birth weight 1,500 g without 293 10 97
major congenital heart disease
result in ischem ia or obstruction (197). Dissection m u st be
II. Birth weight 1,500 g or major 70 29 59
m aintained on the p roxim al esop hagu s to avoid inju ry to
congenital heart disease
the recu rrent laryngeal nerves. III. Birth weight 1,500 g and major 9 7 22
The sim u ltaneou s p resentation of EA/ TEF and d u od e- congenital heart disease
nal atresia is a d ifficult clinical situ ation. Duod enal atresia
d isruption should be m anaged w ith either d irect repair of intra-abd om inal esop hagu s. Recu rrent p neu m onia, reac-
the anastom osis, preferably w ith reinforcem ent w ith an tive airw ay d isease, cyanotic sp ells, and p ersistent anasto-
intercostal m u scle flap or a pleu ral or pericard ial p atch, or motic strictu re can be sym ptom s/ signs of GER in the
w ith form ation of a cervical esop hagostom y and p lacem ent EA/ TEF p atient. GER sym p tom s are p resent in at least 20%
of a gastrostom y tu be w ith su bsequ ent esop hageal rep lace- to 40% of ad u lt p atients w ith p reviou s EA/ TEF (204,205).
ment (200). Strictu re form ation occurs in approxim ately Evalu ation w ith u p p er GI contrast stu d y and / or 24-hou r
15% of cases and is often associated w ith a prior anasto- p H p robe m ay d ocu m ent the d iagnosis (206). GER is typi-
motic leak. Most strictu res are responsive to repeated ante- cally first m anaged w ith prokinetic agents and proton
grad e d ilatation initially at a frequ ency of approxim ately p u m p inhibitors, althou gh ap p roxim ately 30% to 40% of
every 2 to 3 w eeks. Esophagoscopy shou ld be p erform ed p atients requ ire a fu nd op lication (169,203). A 360-d egree
before d ilatation to assess the anastom otic caliber and after N issen fu nd oplication is m ost frequently perform ed ,
d ilatation to ensure that fu ll-thickness perforation has not althou gh a N issen fu nd op lication m ay exacerbate the
occu rred . In narrow strictures, a w ire passed u nd er end o- esop hageal d ysfu nction associated w ith EA/ TEF (207).
scopic and / or fluoroscopic guid ance w ill allow safe passage Und er those circu m stances, recu rrent reflu x, esophageal
of sequentially larger Savory d ilators und er fluoroscopic d ilation and d ysfu nction, and d ysp hagia m ay resu lt in an
guid ance to safely enlarge the anastomosis. Contrast injec- ad verse ou tcome (208). A Thal fu nd op lication is a reason-
tion at the end of the d ilatation can be perform ed to id entify able alternative becau se of the p artial natu re of the w rap,
a leak at the site of the stricture. Rarely, strictures that are bu t the failu re rate has been too high. As a result, the opti-
refractory to routine dilatation require placement of a gas- mal approach is to perform a “flop py” N issen fund oplica-
trostom y tu be w ith m aintenance of a silicone “string” from tion. Since stu d ies have d emonstrated a relatively high
the nares internally to the gastrostom y tu be. The end s of incid ence of Barrett’s esophagitis am ong p atients w ith
the string can be tied externally and tap ed on the infant’s rep aired EA/ TEF (5% to 7%), long-term end oscopic su r-
back, leaving ad equ ate laxity to prevent u lceration at the veillance of these p atients is im p ortant (205,209).
nose or gastrostom y sites w hile m aintaining enou gh ten- Tracheom alacia resu lts in strid or and a barking cou gh
sion to keep from p ulling ou t the string. Vigorou s d ilations in new borns, althou gh som e p atients m ay p resent w ith
w ith Tu cker d ilators can then be p erform ed on a recu rring ap nea, as the resu lt of a w eakness in the tracheal w all such
basis. Occasionally, refractory strictures m ay requ ire resec- that the anterior and p osterior tracheal w alls coap t d u ring
tion or even esop hageal rep lacem ent; althou gh refractory exp iration. Bronchoscop y d u ring sp ontaneou s breathing
strictu res are m ost often d u e to th e p resence of reflu x an d d em onstrates the collap se in the d istal third of the trachea.
u su ally resp ond to d ilatation once a fu nd op lication has Mild sym p tom s in m ost p atients can be follow ed w ith
been p erform ed . Thu s, the p resence of GER shou ld be exp ected resolu tion as the p atient grow s. Life-threatening
investigated if a strictu re d oes not resp ond after tw o or sym p tom s requ ire op eration in 6% (169). An aortop exy, in
three d ilatations. w hich the anterior asp ect of the aortic arch is ap p roxim ated
Leak from th e trachea or com p rom ise of the trach eal to the p osterior sternu m , is effective in alm ost all patients
lu m en is u nu su al bu t requ ires op eration in the form er at resolving the sym p tom s of tracheom alacia (210). A Pal-
and bronchoscop ic evaluation in the latter. Recurrent TEF maz airw ay stent or tracheostom y may be of benefit should
occu rs in 3% of cases, is u su ally associated w ith a p ostop er- the aortop exy fail (211). Frequ ently, it is d ifficult to d eter-
ative leak, and requ ires reoperation, w ith d ivision and liga- mine w hether the sym ptom s observed are d u e to tracheo-
tion of the fistu la (169). Recu rrent pneu m onia, cou ghing, malacia, strictu re, or GER (212).
and choking are frequ ently noted . Esop hagoscopy w ith the Esop hageal d ysm otility is p resent in the m ajority of
patient p rone or balloon catheter obstru ction of the d istal EA/ TEF child ren, and 40% to 75% of ad u lt EA/ TEF
esophagu s d uring esophageal contrast ad m inistration can p atients have m ild -to-severe d ysp hagia and esophageal
enhance id entification of the fistu la. H igh-resolu tion CT d ysm otility (204,205,213,214). In m ost cases, the d ysphagia
may help to id entify a recurrent fistu la or a m issed p roxi- is tolerable and in infants can be m anaged by feed ing w hile
mal fistu la (201). Thoracotom y w ith fistu la ligation is the p atient is sitting u p . An occasional p atient d evelop s a
requ ired . A 2-French balloon catheter shou ld first be p assed d iverticu lu m p roxim al to the anastom osis that requ ires
throu gh the fistu la u nd er bronchoscopic guid ance to allow resection. Scoliosis d evelop s in 8% of p atients, probably
intraop erative id entification of the fistula. Once the fistu la d u e to fu sion of the ribs at the site of the thoracotom y,
is ligated , a p leu ral or pericard ial flap should be interp osed w hich p revents ip silateral sp ine grow th and resu lts in ante-
betw een the trachea and esophagu s to help p revent recu r- rior chest w all d eform ities in 20%, thou gh a m u scle-spar-
rence. Injection of fibrin glu e into the fistula m ay resu lt in ing or thoracoscopic (see below ) approach m ay d ecrease
closu re of the com m unication w ithou t thoracotom y (202). the incid ence of this com p lication. Foreign bod y im paction
The m ost com m on long-term p roblem s associated w ith occu rs in 13% of p atients w ith corrected EA/ TEF usually
EA inclu d e GER (40% to 60%), tracheom alacia (16%), and d u ring the child ’s first 5 years of life (215).
esop hageal d ysfu nction (169,203). GER is likely d u e to the A thoracoscop ic app roach has been ad vocated by som e
tension p laced on the d istal esop hagu s w ith com p rom ise of centers to avoid the complications associated w ith the tho-
the native antireflu x m echanism s and shortening of the racotomy (216). In a multi-institutional retrospective review
(217) of 104 patients w ho und erw ent thoracoscopic EA/ TEF

repair, 11.5% d eveloped an early leak or stricture and a third
needed esophageal dilation at least once. Tw o infants d evel-
oped a recurrent fistula and 24% required a subsequent
laparoscopic fund oplication. In another retrospective com-
parison of the thoracoscopic and open techniques (218), a
minimally invasive approach allow ed d ecreased postopera-
tive narcotic use, shorter time to extubation, earlier feed ing
by mouth, and d ecreased length of stay, w ithout an increase
in operative time, anastomotic leaks, strictures, or mortality.
Anesthetic considerations and potential complications dur-
ing thoracoscopic EA/ TEF repair are significant (219).
■ Congenital diaphragmatic hernia

CDH occu rs d u e to failu re of the pleu roperitoneal canal to
close at 6 to 8 w eeks of d evelopm ent. The d iaphragm atic
d efect is in the p osterolateral aspect and is referred to as
Bochd alek hernia. The CDH is left sid ed in 78% and typ i-
cally contains the sm all and large intestine and the spleen
and m ay contain the stom ach and the left lobe of the liver
(220). With a right CDH , the liver and the abd om inal vis-
cera are typ ically in the hem ithorax. CDH rem ains one of
the most challenging for ped iatric su rgeons, though the rel-
atively high inp atient mortality rate of approximately 50%
has im p roved over the years to a survival of 69% even
thou gh the su rvival of those that requ ire ECLS has
d ecreased to 51% (221,222). The high m ortality rate is
related to the effect of the herniated abd om inal viscera on
the d evelop ing heart and lu ngs, althou gh d evelopm ental
stu d ies in anim als su ggest that the lu ng hyp op lasia m ay
preced e the d iap hragm atic d efect and serve as the p rim ary FIGURE 52.18. Congenital diaphragmatic hernia (CDH). Note the lip of the
insult (223,224). diaphragmatic defect (black arrow) and the left lobe of the liver that is at the
By w hatever m echanism , both the ip silateral and con- opening of the defect. In some cases, the left lobe of the liver may actually
tralateral lu ngs are hypoplastic, w ith the alveolar nu m ber reside in the left chest. The small bowel is seen in the left hemithorax. The
heart is shifted to the right. The major complications in patients with CDH are
on the ip silateral sid e d ecreased by at least 90% and the pulmonary hypertension and lung hypoplasia. The latter is demonstrated in
contralateral lu ng d ecreased by 60% (Fig. 52.18) (225). this image by the small lung to the right of the heart and a diminutive lung on
There is a m arked red u ction in the nu m ber of alveoli and the left (white arrow).
pulmonary arterial branches. In ad d ition, p ulmonary arter-
ies in new borns w ith CDH d em onstrate a thickened m ed ia gas exchange, resu lts in fu rther increases in Pa CO 2 and
w ith the p resence of abnorm al sm ooth m u scle in sm all red u ctions in Pa O 2 and p H . All these variables au gm ent
arterioles (226). As a result of a d ecrease in the total cross- p u lm onary arterial vasosp asm , fu rther increasing the
sectional area of the pulm onary arterial vessels, along w ith right-to-left shu nt and red u cing p u lm onary blood flow. A
increased m u scu larization of sm all arteries, w hich p ro- viciou s cycle as d escribed above p ersists, w hich, if not
motes vasosp asm , p u lm onary hypertension persists in the interru p ted , can resu lt in severe resp iratory failure and
perinatal p eriod w hen it is necessary for pulm onary p res- d eath. Ou tcom e in CDH ap p ears to d ep end on the d egree
su res to d rop in ord er to transition from fetal to new born of p u lm onary hyp op lasia and reactive p u lm onary hyp er-
circulation. Thu s, p u lm onary hypop lasia is represented by tension (228,229).
abnorm al d evelop ment of the airw ays (d ecreased nu m ber Most p atients w ith CDH p resent in the first 24 hou rs,
of alveoli and airw ays), vascu lature (d ecreased nu m ber of althou gh ap p roxim ately 10% to 20% p resent later (230).
vessels and thickened m ed ia), and interstitium (increased The d iagnosis of CDH is typ ically m ad e on chest rad i-
tissu e d ensity), affecting pu lm onary comp liance, gas ograp h w here bow el in the chest, along w ith m ed iastinal
exchange, and p u lm onary arterial pressu res (227). shift to the sid e op p osite the hernia, is noted . An u pper GI
Furtherm ore, p ostnatal fetal circulation persists w ith contrast stu d y can be confirm atory if there is qu estion of a
right-to-left shu nting of blood across the foram en ovale hiatal hernia, a congenital cystic lesion of the lu ng, or an
and patent d u ctu s arteriosu s. This shunting, in conju nction eventration. Su rvival is related to the size of the d iap hrag-
w ith the p resence of p ulm onary hypop lasia, w hich inhibits m atic d efect, an d the stom ach ’s location m ay act as a
surrogate for d efect size. Thu s, the presence of the stom ach com p lications of in utero CDH repair or op en tracheal liga-
in the chest is associated w ith 30% survival, but su rvival is tion is early onset of labor, w hich m ay be red uced by the
nearly 100% if it is in the abd om en (231,232). The ability to less-invasive FETO end oscop ic ap p roach (244,245).
red u ce Pa CO 2 40 m m H g w ith reasonable levels of ventila- At the time of birth, a nasogastric tu be shou ld be
tion also p red icts survival (233). inserted to avoid GI d istension. An end otracheal tu be
In 60% of fetu ses w ith CDH , the d efect is id entified shou ld be p laced for ventilation. Bag m ask ventilation
prenatally d u ring initial u ltrasou nd screening, thou gh should be avoid ed because of the risk of gaseou s d istension
right-sid ed CDH is d iagnosed far less frequ ently (234). of the viscera both in the abd om en and the chest. An um bil-
Those infants w ho are id entified in utero shou ld be d eliv- ical arterial line is p laced and intravenou s access estab-
ered at a center that has capabilities of perform ing state-of- lished . An u m bilical venou s catheter m ay result in vessel
the art care for the new born w ith CDH , inclu d ing ECLS. d isru p tion d u e to the angu lation of the vessels in the
Am niocentesis shou ld be perform ed to establish the kary- rotated liver if the left lobe is in the chest (246). After stabi-
otyp e since trisom y 13, 18, and 21 m ay be associated w ith lization, a right rad ial artery blood gas shou ld be evalu -
CDH . The fetu ses are screened for associated anom alies ated . Conventional m echanical ventilation techniques
using u ltrasound , and an assessm ent of the liver p osition is should be applied w hile avoid ing ventilator-ind uced lu ng
m ad e. Lack of liver herniation is associated w ith excellent inju ry, w hich can resu lt in acu te lu ng d eterioration and
su rvival (93%) w ithou t the need for ECLS in m ost instances chronic lu ng d isease. An arterial oxygen satu ration 85%
(235). At an increasing rate, fetal MRI is u sed to assess lu ng and a Pa CO 2 60 m m H g are accep table. H igh-frequency
volu m es, as these m easu rem ents have been show n to cor- oscillatory ventilation can be ap p lied , althou gh it is qu es-
relate w ith prognosis p ostnatally (236,237). The lu ng-to- tionable w hether this enhances su rvival (247,248). Ap plica-
head ratio (LH R m ultip lication of the length and w id th tion of inhaled nitric oxid e in new borns w ith CDH m ay
of the right lu ng d ivid ed by the valu e of the head p erim e- actu ally increase the need for ECLS (249). Echocard iogra-
ter) can be calcu lated u sing prenatal u ltrasou nd , bu t is of p hy shou ld be p erform ed to evalu ate for congenital heart
higher p red ictive valu e w hen assessed w ith MRI (238). An d isease.
LH R of 1 portend s a poor prognosis w ith valu es 0.97 If gas exchange cannot be enhanced , ECLS is instituted ,
representing the severest form of CDH and an LH R 1.4 p referably p rior to m arked card iop u lm onary d eterioration
ind icating an excellent prognosis (239–241). Unfortu nately, (250). An oxygenation ind ex [(m ean airw ay pressure
these calculations have d ram atically d ecreased pred ictive FIO 2/ Pa O 2) 100] of 25 is an ind ication for ECLS. ECLS
valu e for p atients w ith a right-sid ed CDH . allow s for lu ng rest, resolu tion of p u lmonary hypertension,
A strategy emp loyed for p renatally d iagnosed severe and avoid ance of ventilator-ind u ced lu ng inju ry w hile pro-
CDH involves ex-u tero intrap artu m treatm ent (EXIT) w ith vid ing ad equ ate gas exchange. Venoarterial access via the
initiation of ECMO (ECMO/ ECLS, EXIT-to-ECMO). With right carotid artery and the right internal ju gu lar vein is
this ap p roach, p atients are d elivered by Cesarean section, often u sed becau se this configu ration p rovid es card iac su p -
bu t m aintained on placental sup port w hile cannu lae are p ort. Patients w ith CDH w ho requ ire ECLS have low er left
placed and ECMO initiated . Survival has been d emon- ventricu lar m ass and associated hem od ynam ic com p ro-
strated to be an im pressive 64% using an EXIT-to-ECMO m ise and , therefore, m ay requ ire card iac su pport (251).
strategy in p atients w ith p renatal LH R 1.4 (242). Prop o- H ow ever, a d ou ble-lu m en venovenou s configu ration pro-
nents of this ap p roach favor the associated gentle ventila- vid es ad equ ate su p p ort in m ost CDH p atients and has the
tion, stability of the fetu s d u ring d elivery and cannu lation, ad vantages of avoid ing carotid artery ligation, provid ing
and controlled , p lanned approach to d elivery. H ow ever, w ell-oxygenated blood to the lu ngs and the heart, and m in-
op p onents of the strategy qu estion w hether su rvival is im izing the risk for arterial em bolization (252).
ind eed enhanced by this app roach, w hich requ ires high H emorrhagic complications are the most common clini-
resou rce u se and cost. Fu rtherm ore, cu rrent prenatal ou t- cal complications, d ue to anticoagulation, occurring in 43%
com e p red ictions are su fficiently inaccu rate su ch that the of patients overall. The most common locations for bleed ing
m other and fetu s m ight be p laced at increased risk and are a su rgical rep air site (24%), head (11.5%), cannu lation
com p lications of Cesarean section, ECMO, and the EXIT- site (7.5%), and GI site (5%) (253). Bleed ing complications
to-ECMO approach w hen such invasive strategies might are most common in those u nd ergoing d iaphragmatic her-
not otherw ise have been requ ired . nia repair w hile on ECLS (58%). When controlling for fac-
Another ap proach to the prenatal treatm ent of CDH tors associated w ith severity of CDH , d elayed repair after
involves in utero fetal end oscopic tracheal occlusion (FETO). ECMO therapy has been associated w ith increased survival
With this technique, an occlusive balloon is inserted via (254). As a result, it is generally preferred that d iaphrag-
transu terine bronchoscopy into the fetal trachea at 26 to 28 matic hernia repair be d elayed until the patient has w eaned
w eeks w ith planned removal at 34 w eeks. In patients w ith from ECLS or is just about to be removed from extracorpo-
left-sid ed CDH and low LH R, the associated tracheal occlu- real sup port, although som e su rgeons are recom m end ing
sion has d em onstrated an im provem ent in LH R from 0.7 to early repair on ECMO. When operation on ECLS is
1.8 over a 2-w eek period and an increase in su rvival from required , ad m inistration of am inocaproic acid m ay red u ce
15% to ap proxim ately 50% (234,243). One of the m ajor bleed ing comp lications (255). Factors influ encing su rvival
of p atients w ith CDH on ECMO inclu d e initial blood gases,

card iac d efects, and renal failure, bu t not the tim ing of su r-
gery (256).
The op eration for CDH is no longer an em ergency. In
fact, su rvival m ay be increased and the need for ECLS
d ecreased if a d elayed approach to the rep air of the
d iaphragm atic d efect is taken, although som e stu d ies d is-
pute this ap p roach (257–259). Either w ay, a d elay in rep air
d oes not ap p ear to be d etrim ental, and thus, in m ost cen-
ters, the d iap hragm is repaired once the physiologic issu es
have resolved . Typ ically, the d efect is ap proached via a
subcostal incision, althou gh a thoracic app roach can be
used . In ap p roxim ately 20% of patients, a sac consisting of
peritoneu m and p leu ra that contains the herniated viscera
is present and m u st be excised to allow fu ll lung expansion.
The viscera are carefully red uced . If the patient has been on
ECLS, the sp leen and liver are enlarged and p rone to FIGURE 52.19. A thoracoscopic congenital diaphragmatic hernia repair
inju ry. Extralobar sequ estration is observed in som e begins by using pledgets sutured to anchor the lateral border to the ribs.
p atients w ith CDH and shou ld be resected w ith care to Medial sutures were placed later to complete the repair.
control the system ic arteries extend ing throu gh the infe-
rior p u lm onary ligam ent from the aorta to the sequ estered
lobe. The p osterior leaf of the d iap hragm typ ically has to w hich can ind u ce a shift in the m ed iastinu m w ith associ-
be freed from the p eritoneu m , after w hich an assessm ent is ated hem od ynam ic com p rom ise (151).
m ad e of w hether su fficient d iap hragm is p resent for p ri- In general, the abdomen is closed primarily. Alternatively,
m ary rep air. If so, 3–0 Prolene m attress su tu res are u sed abdominal wall closure may not be possible because the peri-
for the rep air. In ap p roxim ately 50% of p atients, a p atch is toneal cavity is poorly d eveloped. Mesh closure of the
requ ired to com p lete the d iap hragm atic closu re (220). Typ - abdominal wall or even placement of a silo may be necessary
ically, inad equ ate m u scle is p resent p osterolaterally. Use of to avoid the complications associated w ith increased intra-
prosthetics su ch as Goretex (W.L. Gore and Assoc., Inc., abdominal pressure (see section on abd ominal wall defects)
N ew ark, DE) or sm all intestinal subm ucosa m esh (Su rgisis and compromise of diaphragmatic excursion in a patient
ES; Cook Tissu e Engineering Prod u cts, Bloom ington, IN ) with concomitant CDH and respiratory insufficiency (264).
allow s a loose rep air bu t m ay be associated w ith high rates Thoracoscopic approach to CDH repair is an effective
(40% to 80%) of d iap hragm atic hernia recu rrence, esp e- strategy in patients after stabilization, though 20% w ere con-
cially w hen little or no d iaphragm atic m u scle is present verted to open repair (265). Most conversions to open repair
(260–262). In ad d ition, w ith u se of a prosthetic, the risk of are due to hypercarbia, card iopulmonary instability of the
infection is low bu t present. Posterior su tu res of 3–0 Pro- CDH patient w ith alread y compromised heart and lung
lene are all placed and then tied to approxim ate the pros- function, or need for patch closure, w hich may be performed
thesis to the m u scle. The patch is app roxim ated to the ribs via the thoracoscope, but may be technically challenging
w here the native d iaphragm is absent. The need le is p assed (266). Id eal cand id ates for the thoracoscopic repair includ e
arou nd ind ivid ual ribs to p rovid e a strong closu re. One preoperative factors such as minimal ventilatory support,
must be careful to ensure that bow el d oes not get entrapped presence of the stomach in the abd omen, and the lack of pul-
betw een the sutu res or the p atch and the rib. monary hypertension (Fig. 52.19) (267). Laparoscopy is id eal
An alternative is to u se an internal obliqu e and trans- for repair of patients w ith Morgagni-type d iaphragmatic
versalis m u scle flap to close the d iap hragm atic d efect, hernias w ith a high success rate (268,269).
w hich m ay red u ce the risk of recu rrence (263). To d o this, Postoperative com plications are pred om inantly associ-
the m u scle is sep arated from the external obliqu e at the ated w ith the card ioresp iratory sequ elae associated w ith
upper asp ect of the su bcostal incision and fold ed d ow n- CDH . Chylothorax occu rs in 10% of p atients after repair
w ard . Division of the posterior low er ribs aid s in creating and is increased am ong those p atients requ iring ECLS
the flap ; how ever, extensive d issection should only be (270). In one series (271), those p atients w ho d eveloped
und ertaken if the risk for im m inent initiation of ECLS and chylothorax w ere left sid ed and associated w ith patch
associated anticoagu lation is low. Likew ise, correction of repair. N early half the patients w ere refractory to octreotid e
the typ ical m alrotation w ith a Lad d p roced u re is p er- and requ ired pleu rectomy for m anagement, w ith one d eath
form ed only if it ap pears u nlikely that ECLS w ill be occurring from septic complications. Recurrent hernias are
requ ired . An ap p end ectom y is specifically not perform ed if managed w ith transabd ominal reoperation and generous
a p rosthesis has been p laced becau se of the risk of infec- use of a patch to d ecrease tension on the rep air. The survival
tion. A chest tu be m ay be placed , althou gh one m u st be rate for patients w ith CDH is 63% (220). Associated anom-
carefu l to avoid application of excess negative pressu re, alies are p resent in 40% of new borns w ith CDH and m ost
com m only involve heart d efects (63%) (271). The com bina- p revented by ad m inistration of intravenou s fluid s, w rap-
tion of CDH and congenital heart d isease confers a w orse p ing of the viscera w ith a gau ze d ressing, and p lacem ent of
prognosis (41%), especially in those w ith univentricu lar the low er p ortion of the new born’s bod y in a bow el bag.
d isease (5%) (272). The viscera shou ld be su p p orted by the gau ze so that they
The long-term m orbid ity in p atients w ith CDH is su b- rem ain on top of the abd om en, rather than falling over to
stantial. Chronic lung d isease is p resent in 50% of su rvivors the sid e, to avoid vascu lar obstru ction, esp ecially venou s
at 1 year of age (273). In m ost patients, pulmonary fu nction ou tflow obstru ction, w hich can lead to increased bow el
norm alizes over tim e, although pu lm onary blood flow to ed em a. Broad -sp ectru m antibiotics shou ld be ad m inistered
the ip silateral sid e rem ains red uced , especially in those to p revent infection.
patients w ho requ ired ECLS (274,275). GER is evid ent in u p After resu scitation, the new born is taken to the op erat-
to 81% of p atients at the tim e of d ischarge and in 50% at 1 ing room . The size of the peritoneal cavity is often lim ited
year (276). The esophagus is ectatic in 70% of patients w ith and can make safe red u ction of the viscera challenging. Rec-
CDH , likely related to kinking of the gastroesop hageal tal irrigation is performed , along w ith manual massage of
junction w hen the stom ach is in the hem ithorax (277). Tu be the intestines, to evacuate as much meconium as possible,
feed ings are required in over half of the patients at the tim e thus red ucing the volume of the intra-abd ominal contents.
of d ischarge, bu t m ost are tolerating oral feed s w ithin the Likew ise, a Foley catheter is inserted to d ecompress the
first few years. Malrotation is present in m ost p atients w ith blad d er. After establishing a sterile field , the fingers are
CDH . The incid ence of subsequent volvulus is 3% to 9% used to stretch the anterior abd ominal fascia in an attempt
(278,279). Bow el obstruction occu rs in approxim ately 10%. to enlarge the peritoneal cavity if need ed . The small and
Sp inal and chest w all abnorm alities are p otential long- large bow els are typically m atted together w ith a peel on
term p roblem s in child ren w ith CDH and inclu d e p ectu s the surface; they can be ed ematous, thickened , foreshort-
d eform ities in 33% and thoracic sp ine scoliosis in 12% ened , and , at tim es, ischem ic-appearing. The bow el shou ld
(279). A thoracoscopic approach to the repair m ay amelio- be hand led gently and operations on the bow el generally
rate p roblem s w ith scoliosis, w hich app ears to be related to avoided. Any attempt to remove peel risks bowel injury,
the thoracotom y incision (268). includ ing perforation, and development of an enterocuta-
Develop m ental d elay classified as m ild or m od erate is neous fistula. When jejunoileal atresia is id entified , a pri-
evid ent in 45% of patients, but these find ings tend to mary anastomosis should be performed only if the ed ema
im p rove over tim e. Those m anaged w ith ECLS d em on- and peel are minimal. Otherwise, there is a reasonable risk of
strate severe neu rologic abnorm alities in 20% to 40% of anastomotic leak and stricture. In most cases (80%), the atre-
patients. H earing d eficits are observed in 21%. sia should be left intact at the initial operation (280). The
bowel should be re-explored at 3 to 4 w eeks with repair of
the atresia. If a silo w as placed initially, the bow el should be
■ ABDOMINAL WALL DEFECTS evaluated at the time of fascial closure and a primary resec-
tion of the atresia w ith anastomosis performed if the thick-
■ Gastroschisis ening has resolved. In some circumstances, an enterostomy
The new born w ith gastroschisis has a sm ooth 2- to 5-cm is required, especially in the setting of colonic atresia.
op ening alm ost alw ays to the right of an intact u m bilical Prim ary closu re of the abd om inal w all is su ccessfu l in
cord throu gh w hich the stom ach, sm all intestine, and colon ap p roxim ately 80% of new borns (281,290). The viscera are
are typ ically herniated . The liver is almost never eviscer- gently red u ced w hile avoid ing tw ists in the m esentery.
ated , and associated anom alies are mostly lim ited to those The ed ge of the op ening is incised and the fascia id entified
of the GI tract w here the bow el is often short and intestinal circu m ferentially. Vicryl su tu res are then p laced to close
atresia occu rs in 10% to 15% (280). the fascia; this is often d one in a horizontal fashion
Prenatal d iagnosis via ultrasound occurs in most infants becau se the tension is less than w ith a vertical fascial clo-
(281). Controversy exists as to w hether new borns d iagnosed su re. Com m u nication betw een the su rgeon and the anes-
in utero should be delivered early by Cesarean section to pre- thesiologist allow s recognition of ad verse effects of the
vent injury to and swelling of the exposed bow el (282,283). closu re: significant increase in airw ay p ressu res, com p ro-
How ever, there is evidence to suggest that there is minimal, m ise of hem od ynamics, or d evelopment of acid osis d u e to
if any, advantage to preterm or Cesarean section delivery excess intra-abd om inal pressu re. Exam ination of the new -
(284–289). At this point, the optimal tim ing of d elivery is born’s thighs may d emonstrate cyanosis d u e to venou s con-
uncertain, although most clinicians are convinced that gestion. Intra-abd om inal p ressure may be measured via the
Cesarean section is not required for gastroschisis. nasogastric or blad d er catheter. If signs of increased abd om -
At the tim e of d elivery, a nasogastric tu be shou ld be inal pressu re are observed , the bow el shou ld be rem oved to
placed to p revent vomiting and aspiration. The bow el d ecomp ress the abd omen and a silo p laced (see below ). At
shou ld be exam ined and any tw ists in the m esentery or times, the viscera may be successfully red uced , but fascial
constriction of the viscera from a sm all opening relieved closu re lead s to p hysiologic com p rom ise. In that case, a
im m ed iately to avoid vascu lar com promise. Dehyd ration Vicryl or sm all intestinal su bm u cosa m esh (Su rgisis ES;
and hyp othermia from insensible flu id and heat losses are Cook Tissue Engineering Prod u cts, Bloomington, IN ) may
and edema of the legs and low er abdomen, and compro-

mised ventilation are all ind ications for silo placement or
release of the umbilical tape on the silo. Patients w ith gas-
troschisis have an approximately 50% increase in fluid
requirements w hen compared w ith other new borns (292).
There is a grow ing trend tow ard placement of a silo
rather than attempting to close the abd omen primarily (293).
It has been suggested that primary closure may be traumatic
A to the bow el and place the new born at risk for physiologic
compromise and pulmonary barotraum a (294). Spring-
loaded silo placement can be performed at the bedside in the
new born intensive care unit (ICU). Closure of the gastroschi-
sis d efect can then occur once the viscera are red uced . This
approach may be associated with a decrease in time on the
mechanical ventilator, time to initial and full feed ings, and
complication rate (293). H ow ever, one must monitor the
bowel in the silo for venous congestion w ith removal and
readjustment of the silo to prevent bow el infarction w hen
such is observed (295). In ad d ition, it is im portant to avoid a
funnel shape into a small abd ominal w all opening d uring
reduction of the intestinal contents of the silo as this can lead
B to bow el ischem ia. Rather, a cylind rical shape, w ith expan-
sion of the gastroschisis opening w hen necessary, can allow
FIGURE 52.20. A: A preformed, spring-loaded silo (Specialty Surgical
Products, Victor, MT) used to contain the bowel in patients with gastroschisis. for grad ual red uction w ithout compression the of bow el
B: The silo is in place with the round, spring-loaded base inside the peritoneal contents at the base and resultant bow el ischemia.
cavity. The umbilical tapes are tied sequentially lower to reduce the bowel Postoperative complications, in ad d ition to those men-
into the abdomen over a period of days. tioned earlier, includ e d elay in return of GI function
(med ian time to initiation of feed ings is 15 d ays w ith full
be u sed to au gment the fascia, althou gh a ventral hernia enteral intake achieved by 22 d ays) (296). Su pport w ith par-
may result. Failure to recognize the signs of increased intra- enteral nu trition is required in m ost patients. As such, cen-
abd ominal pressu re may lead to red uced visceral and renal tral access shou ld be achieved early in the course, although
blood flow and associated bow el necrosis and renal failu re. catheter-related sepsis is a potential complication. Postoper-
If the bow el cannot be safely reduced, a staged closure ative bow el obstruction is relatively u ncommon and an
using a prosthesis is useful. Spring-load ed preformed silos upp er GI contrast stu d y is performed only after approxi-
are now available in different sizes and are easy to place, mately 3 w eeks w ithout return of GI function. Patients w ith
which precludes the need to manually construct the silo and gastroschisis are also at risk for infection as long as the
to sew the silo to the relatively tenuous fascia (Fig. 52.20) silo is in place; as a result, broad -spectrum antibiotics are
(291). In some cases, the abdominal w all defect is enlarged to ad ministered w hile the silo is in place. The comp lication of
avoid a funnel-type configuration of the silo, which could silo separation from the fascia, w hich often occu rred after 7
lead to compression of the bowel at the base of the silo with to 10 d ays, has d iminished w ith application of the spring-
ischemia and necrosis. The silo is wrapped in Betad ine-mois- load ed silo. If this com plication occu rs, a pseud om em brane
tened gauze to prevent infection and suspended from the has usually form ed beneath the silo, w hich can be allow ed
overbed warmer to encourage gravity-assisted reduction of to granu late. Skin graft closu re of the abd ominal w all is pos-
the remaining viscera. Over the ensuing days, the viscera are sible once infection has been resolved using topical silver
gradually reduced by compressing or twisting the silo and sulfad iazine.
tying an umbilical tape sequentially lower on the silo every N ecrotizing enterocolitis (N EC, see below ) is a com pli-
12 to 24 hours. One must be careful to avoid injury to the cation that m ay be observed d u ring ad vancem ent of
bowel during these maneuvers; the silo is constructed of a enteral feed s after gastroschisis closu re (297). The risk for
transparent material specifically to allow monitoring of the N EC in the setting of gastroschisis m ay be increased d ue to
bowel’s status. The viscera are usually reduced w ithin a enhanced m u cosal p erm eability of the bow el, w hich is
week such that the base of the silo is flat. The patient is then thickened and inflam ed as a resu lt of exp osu re to the am ni-
taken back to the operating room and the fascia closed as otic flu id in utero or d u e to intestinal d ysm otility or intes-
described earlier. tinal atresia. Those w ith gastroschisis w ho d evelop N EC
Postoperative mechanical ventilation is required in most have a low er birth w eight and are m ore likely to be for-
newborns, and care should be taken to avoid ventilator- mu la-fed (298). An enterocu taneou s fistu la m ay d evelop
induced lung injury as a result of high intra-abdominal pres- from an anastom otic leak or a suture-ind u ced intestinal
sure. Oliguria unresponsive to fluid administration, cyanosis inju ry. Malrotation, if not corrected at the tim e of the initial
operation, m ay result in jejunal obstru ction d u e to Lad d red u ction except for w here it is ad herent to the liver. To
band s or volvu lu s. SBS m ay occu r as a resu lt of bow el d ys- excise the sac in that location cou ld result in liver inju ry and
fu nction or loss of bow el d u e to atresia or associated w ith bleed ing. Should bleed ing occu r, pressu re- and clot-enhanc-
many of the complications outlined previously. By 6 months ing agents should be ap plied . Unfortu nately, once the sac is
of age, intestinal fu nction, in general, has returned to nor- excised , red u ction m u st be achieved w ithin a reasonable
mal. GER is observed in 16% of patients w ith gastroschisis, period of time to avoid sep tic complications. Some surgeons
likely related to the p resence of increased intra-abd ominal have recommend ed leaving the sac intact and sequentially
pressu re (299). Su rvival is 90% (281,300). gathering the sac to achieve red uction (305). Alternatively,
mesh can be sutured to the skin–amnion junction and pro-
gressively tightened to red u ce the bow el and liver w ithin
■ Omphalocele the abd omen (306). Once red u ction is accomplished , the
In contrast to gastroschisis, an om phalocele consists of an linea alba is approxim ated , leaving the am nion intact,
abd om inal w all d efect at the u mbilicus, a peritoneal and allow ing staged red u ction w ithout a commitment to rap id
am nion covering or sac, a normal u mbilical cord that closure. If the mesh separates, the sac is still in place.
attaches to the sac, and um bilical vessels that rad iate over Most recently, surgeons have approached giant omphalo-
the d efect. These characteristics of an om phalocele allow celes by compressing the omphalocele via wrapping with ace
d ifferentiation from a gastroschisis, even w hen the sac ru p - bandages and simply allowing the sac to epithelialize over a
tu res in ap p roxim ately 10% of cases (301). The liver is p res- number of months (307–309) (Fig. 52.21). Application of Sil-
ent in approxim ately half of the d efects. vadene, rather than mercurochrome, which can cause mer-
Associated anom alies are present in approxim ately 30% cury poisoning, results in eschar formation of the sac. To
to 60% of new borns w ith om phalocele and are a sou rce of
major m orbid ity and mortality for su ch p atients (302). Con-
genital heart d isease occu rs in 20% and m ay increase op er-
ative risk (303). Abnorm al karyotypes are observed in 29%
and the Beckw ith–Wied em ann synd rom e in 10% (304). The
latter p atients have m acroglossia, w hich can obstru ct the
airw ay, and m ay have hypoglycemia, w hich requ ires p re-
op erative recognition and treatm ent.
The initial m anagem ent of om p halocele is sim ilar to
that p reviou sly d escribed for gastroschisis. Prevention of
hyp otherm ia and d ehyd ration is param ount. Treatm ent
w ith broad -sp ectrum antibiotics is initiated . End otracheal
intu bation and m echanical ventilation are frequ ently
requ ired . The sac is left intact and is covered w ith m oist
nonad herent gau ze to prevent d esiccation and to d ecrease
heat and flu id losses. Multiple layers of w rapping m ay be
A
necessary to p revent heat loss; how ever, it is im p ortant to
keep the und erlying sac intact and prevent its rup tu re.
Evalu ation for other chrom osom al and d evelopm ental
anom alies, esp ecially those that are card iac, is u nd ertaken.
If the d efect is 4 cm in size, it is consid ered a hernia of
the u m bilical cord . Closu re of a d efect of this size is fairly
straightforw ard and p rim ary closu re shou ld be p erform ed .
The m anagem ent of om p haloceles 4 cm is m ore challeng-
ing and com plicated and is associated w ith a poorly d evel-
oped p eritoneal cavity. Coverage of the om phalocele d efect
is the p rim ary goal. The skin–am nion ju nction is incised
circu m ferentially and the fascia m obilized ; cau tion shou ld
be exercised w hen d issecting over the superior asp ect of
the liver since the hep atic veins are often su p erficial in this
location becau se of the d ow nw ard position of the liver in
the om p halocele. Inju ry to and bleed ing from the hep atic
veins can resu lt. Exam ination of the d iaphragm shou ld be B
perform ed in case an associated d efect is present.
With a large om phalocele, prim ary closure is rarely p os- FIGURE 52.21. A: An omphalocele at birth. Note the dark area on the supe-
rior aspect (arrow), which denotes the liver in the omphalocele. The omphalo-
sible. Thus, staged red uctions are typically employed . Tra- cele was treated expectantly with compression wrapping and Silvadene.
d itionally, the omphalocele sac is excised d uring staged B: Note the reduction in the size of the omphalocele over the ensuing months.
d ecrease the incid ence of neu trop enia w ith chronic Sil- GER is high (43%), likely d u e to the effects of elevated
vad ene u se, bacitracin can be u sed on alternating d ays. It intra-abd om inal p ressu re (300). Ventral hernias frequently
is im p erative that the om p halocele w rap p ing shou ld “not need to be ad d ressed , esp ecially in those in w hom a nonop-
d istort the sac, be too tight at the base, or restrict ventila- erative ap p roach w as u nd ertaken. A staged ap proach to
tion” (310). Contraction and flattening of the om p halocele closu re of the ventral hernia is requ ired in those w ith m as-
are often the resu lt, althou gh a m assive ventral hernia u su - sive ventral hernias. The incid ence of cryp torchid ism is
ally rem ains. One m ay be trad ing com p lications associated increased in p atients w ith om p halocele (16%), p resum ably
w ith im m ed iate attem p ts at fascial closu re w ith other chal- becau se of the d ecreased intra-abd om inal p ressu re present
lenges in the fu tu re. d u ring the u su al in utero testicu lar d escent (314).
Another app roach is the creation of a silo from Dacron-
reinforced silastic or Goretex (W. L. Gore and Assoc.,
N ew ark, DE) and su turing it to the fascial ed ges. The m esh ■ ACQUIRED NEWBORN SURGICAL PROBLEMS
is sequentially gathered in the mid line every 12 to 24 hours
until the fascial ed ges are nearly approximated . Du ring this
■ Pyloric stenosis
process, one must balance aggressively tightening the mesh H ypertrophic pyloric stenosis typically presents w ith pro-
w ith avoid ing und ue tension on the mesh; excess tension jectile nonbiliou s vom iting in the new born at 2 to 8 w eeks of
could lead to premature separation of the mesh from the fas- age. Palpation of the up per abd omen reveals the classic
cia. The patient should also be monitored for evidence of “olive” rolling und er the examining hand in 72% of patients
high intra-abdominal pressure resulting in hypercarbia, olig- and in and of itself is an ind ication for op eration (315). The
u ria, hem od ynam ic com p rom ise, and acid osis. Su ch high olive can be easily missed u nless a nasogastric tu be is
p ressu res cou ld com p rom ise ventilation, renal blood flow, p laced to d ecompress the stomach and the infant is quieted
card iac ou tp u t, intestinal p erfu sion, and venou s d rainage w ith feed ing of 5% d extrose w ater. An u ltrasou nd d emon-
from the low er extremities. The intra-abdominal pressure can strating a p yloru s longer than 15 to 19 m m or w ith a w all
be assessed using a nasogastric tube or a bladder catheter and thickness 3 mm is consid ered d iagnostic, although the
should be maintained 20 cm H 2O. Once it is nearly app rox- patient’s age and prematu rity shou ld be taken into account
im ated , the fascia can then be closed w ith rem oval of the to avoid misd iagnosis (316,317). The u ltrasou nd is operator
m esh, althou gh a reasonable op tion is to close the skin d epend ent and may not be accurate if the rad iologist is
w hile leaving part of the mesh in place. If the mesh remnant inexperienced (318). An u pp er GI contrast stud y shou ld
is su bstan tial, su bsequ ent staged op eration s m ay be p er- d emonstrate an elongated , narrow ed pyloric channel and
formed to remove the mesh and to approximate the fascia in “shou ld ering” of the pyloric mass u pon the antru m. The
the mid line. If fascia or skin closure is not achieved w ithin 7 bariu m shou ld be evacuated from the stomach after the
to 10 d ays, the mesh is at risk for becoming infected and stud y via a nasogastric tube to prevent aspiration.
may separate, leaving granulation tissue und erneath and Patients w ith pyloric stenosis have been vomiting and
presenting a challenging w ound care p roblem that may be must be sufficiently resuscitated before operation. Many
complicated by the d evelopment of enterocutaneous fistu- patients w ill have a d egree of hypochloremic, hypokalemic,
lae and sep sis. Application of hom ograft and other artificial metabolic alkalosis (319). Bicarbonate levels 30 mEq/ L are
w ound coverings should be consid ered . One option is to of concern and 35 mEq/ L are even more so. Preop erative
allow th e w ou nd to ep ith elialize (311). An altern ative is resu scitation is ad vised in m ost patients unless the bicar-
split-thickness skin graft placement, w hich is often effective bonate is 30 mEq/ L, the chlorid e normal, and u rine out-
once w ound infection is controlled . pu t excellent by history.
Return of GI function is often d elayed in patients w ith a The stom ach should be aspirated before ind uction of
large om p halocele. Parenteral nu trition support w ill u ni- anesthesia to prevent aspiration even if a nasogastric tube
form ly be requ ired . Mechanical obstru ction can occu r, bu t w as in place prior to operation (320). The pyloric m uscula-
is unu su al. Lu ng and chest w all hypop lasia and chronic ture is divided via a Ramstedt pyloromyotomy w hile the
resp iratory insu fficiency are reasonably com m on am ong mucosa is maintained intact. The operation w as typically
patients w ith giant om phaloceles, and tracheostom y tu be performed using a right upper quadrant transverse incision,
placem ent m ay be requ ired . Staged red uction, w ith its though the supraumbilical and laparoscopic approaches are
associated effect u p on the d iaphragm , is frequ ently com p li- now increasingly more popular (321,322). The laparoscopic
cated by the lu ng d ysfunction. A few p atients, at the p oint approach uses a 5-mm umbilical port for the scope and both
of d elayed ventral hernia closure, d eveloped severe pul- a right and left u pper qu ad rant stab w ound for p lacement
monary hypertension requiring ECLS postoperatively even of 3-mm instruments. With the open technique, the antrum
though no evid ence for pulmonary hypertension w as found is first d elivered , follow ed by “rocking” the pyloru s ou t
on p reop erative echocard iograms. throu gh the incision. Failure to make an incision of ad e-
Su rvival is 80% to 90% and is m ostly related to the quate size w ill make d elivery of the pylorus d ifficult and
im pact of associated anom alies (302,312). Most patients d o potentially resu lt in trauma to the serosa of the antru m or
w ell in the long term and have a good qu ality of life even perforation. From this point, the op en and laparo-
(304,313). In child ren w ith an omphalocele, the incid ence of scopic techniques are similar. Vessels on the surface of the
pylorus are scored w ith the electrocau tery since d eeper use
of cautery may lead to potential injury to the mu cosa. An
incision w ith a knife is then perform ed from a point ju st
proximal to the d u od enu m u p onto the antrum . With the
laparoscopic technique, it is im p ortant to m ake the incision
long enou gh and d eep enou gh to facilitate su bsequ ent Duodenal
spread ing of the pyloric muscle. The back of a knife blad e perforation
(open) or the sheathed arthrotomy knife (laparoscopic) is Approximating
then insinuated into the incision and tw isted to further sutures
spread the ed ges of the pyloric muscle. The pylorom yotomy
Duodenum
spread er is then used to engage the ed ges and complete the
pyloromyotomy. The first spread shou ld be generous to
crack the pyloru s and expose the und erlying mucosa. It is
im portant to engage the sp read er equ ally betw een the FIGURE 52.22. Repair of a duodenal perforation following pyloromyotomy.
The opening in the mucosa is almost always adjacent to the duodenum. Three
ed ges of the p yloru s so that the ed ges are perpend icular or four sutures are placed approximating the mucosa to the seromuscular
rather than oblique, w hich makes completion of the layer of the duodenum. Note that the pyloromyotomy is carried proximally
pyloromyotomy d ifficu lt. In ord er to avoid p erforation, the onto the antrum until the gastric circular fibers are encountered in order to
ensure that the pyloromyotomy is adequate.
pyloromyotomy shou ld not extend onto the d uod enu m.
There is a color change at the pylorod uod enal junction,
w hich, along w ith palpation w ith a finger or instrument,
allow s id entification of the d istal end of the pyloru s. The laparoscopy and m ay contribute to the increased com p lica-
pyloromyotomy shou ld extend proximally onto the antrum tion rates, as the m ajority of p erforations and incom p lete
for approximately 1 cm until the circular muscles of the m yotom ies occu rred in the first 2 to 3 years at high-volu m e
antru m are id entified . Failu re to extend the pyloromyotomy hosp itals (328,329).
proximally to this p oint risks an incomplete pyloromy- Feed ings are often initiated 4 to 6 hou rs after the proce-
otomy and postoperative feed ing intolerance. The mucosa d u re and can be given ad libitu m (330). Em esis in the first
should be visible for the entire length of the pyloromy- d ay or tw o after the op eration occu rs in 44% of patients and
otomy, and the tw o halves of the pylorus should be tested to is thou ght to be second ary to gastritis (331). Persistent
see that they easily move longitud inally separately from vomiting occu rs in ap p roxim ately 5% and u su ally resolves,
each other. A volu m e of 30 to 60 m L of air is injected throu gh althou gh vom iting that p ersists beyond 3 to 5 d ays should
a nasogastric (NG) tube, the duodenum occluded just d istal raise concern for an incom p lete p ylorom yotom y (332). An
to the pylorus, and the stomach compressed w hile observing u p p er GI stu d y w ill not be help fu l in d istingu ishing an
for leak of air or bile from the pyloromyotomy site. Perfora- incom plete pylorom yotom y becau se changes in the
tion of the mucosa occurs in 2% to 4% of patients and is usu- p yloru s are not observed for m any w eeks after ad equate
ally at the duodenal end of the pyloromyotomy. The mucosa p ylorom yotom y. In the case of p rolonged feed ing intoler-
can be closed d irectly w ith a 5–0 Vicryl suture. A better alter- ance, p arenteral nu trition shou ld be initiated . If gastric ou t-
native is to approxim ate the gastric sid e of the opening to let obstru ction p ersists over the next 1 to 2 w eeks,
the pyloric muscle at the d uod enal end w ith interrupted 5–0 reop eration shou ld be consid ered . Ad m inistration of intra-
Vicryl sutu res (Fig. 52.22). Consid eration should be given to venou s or oral atrop ine m ay treat the sym p tom s of p yloric
suturing the omentum to the pyloromyotomy site to rein- stenosis and serve as an alternative to reop eration in this
force the closu re. Alternatively, the serosa of the pyloromy- setting (333). Unrecognized p erforation can be d evastating;
otomy site can be closed w ith 4–0 Vicryl sutures and the the incid ence shou ld be 1%. Any infant m anifesting fever,
pylorus turned 90 or 180 d egrees, w here another pyloromy- lethargy, and / or p hysiologic instability should u nd ergo
otomy is performed . The results of either approach appear u p p er GI contrast stu d y to evalu ate for a leak. The inci-
to be equ ivalent (323). N G suction should be maintained for d ence of w ou nd infections m ay be higher than exp ected for
48 hours after su ch a repair. Small amounts of bleed ing from a clean case (4%), and for that reason, it is recom m end ed
the surface or ed ges of the pyloromyotomy may be seen and that antibiotics su ch as Cep hazolin be ad m inistered in the
w ill uniformly stop w ithout cautery. Cauterizing the p eriop erative p eriod (334). Postop erative w ou nd fascial
mucosa should never be attempted because of the risk of d ehiscence, w hich u sed to be a concern w hen operations
perforation. w ere performed in malnourished infants, is now an unusual
The lap aroscop ic ap p roach has d ecreased com p lication com plication.
rates, esp ecially w ound infections, shorter tim e to fu ll
feed s, red u ced p ostop erative em esis, and red u ced lengths
of stay com p ared w ith the open p ylorom yotom y (324,325).
■ Necrotizing enterocolitis
H ow ever, the lap aroscopic approach is also associated w ith The etiology of N EC is u nclear, bu t the resu lt is hypoperfu-
an increased incid ence of incom plete m yotom y and sion of the m esenteric blood su pply w ith intestinal ischem ia
mu cosal p erforation (325–327). A learning cu rve exists w ith lead ing to bacterial invasion and necrosis. Although it can
occur in full-term new borns, the risk of N EC increases w ith su p rau m bilical incision occu r. The bow el is su tu red to the
gestational age 35 to 36 weeks (335). Administering enteral external obliqu e fascia at four points around the circu m fer-
feed s, especially w ith hyperosmolar solutions, appears to ence of the enterostom y in ord er to p revent the frequ ent
augment the risk of NEC; however, neonates who have com p lication of p eristom al hernia. Typ ically, a m u cou s fis-
never been fed are also susceptible. NEC may be associated tu la is created along w ith the enterostom y, w hich allow s a
w ith either a single site of perforation in 50% of cases or mul- local op eration at the tim e of taked ow n of the enterostom y.
tiple, d iscontinuous segments w ith bow el thinning, pneu- Stom a and w ou nd com p lications occu r in 39% of p atients
matosis, and even frank necrosis, in contrast to id iopathic op erated u p on for N EC and inclu d e w ou nd infection,
spontaneous intestinal perforation (SIP), in w hich a perfora- d ehiscence, and stom al p rolap se, retraction, necrosis, or
tion w ithout associated necrosis is noted on the antimesen- strictu re (342).
teric bord er of the terminal ileum (336). In cases in w hich the extent of d isease is patchy bu t
The m ost d ifficu lt asp ect of the su rgical treatm ent of involves a m inority of the sm all bow el, all ischem ic and
N EC is the d ecision on w hen to intervene operatively. In necrotic regions are excised . In contrast, if the m ajority of
the absence of p neu m op eritoneu m or evid ence for bow el the bow el is com p rom ised , then only frankly necrotic, bu t
necrosis, the p atient is m anaged w ith nasogastric su ction, not ischem ic, areas shou ld be resected becau se of the risk of
broad -spectrum antibiotics, fluid resuscitation, and frequent SBS. The end s of the bow el m ay be ligated w ith re-explo-
m on itoring of hem od yn am ics, u rin e ou tp u t, p latelet ration in 24 to 48 hou rs. Alternatively, if an enterostom y is
cou nt, w hite blood cell cou nt, blood gas valu es, elec- created that is p roxim al to all ischem ic regions su ch that all
trolytes, and abd om inal rad iograp hs. Clinical signs and d istal areas are d efu nctionalized , then re-exp loration m ay
symptom s consistent w ith ongoing sepsis (lethargy, tem- be requ ired only if refractory sep sis d evelop s. Mu ltip le
peratu re instability, ap nea, brad ycard ia, and shock) d espite enterostom ies or anastom oses d istal to the m ost p roxim al
antibiotic therapy, an erythematou s or d iscolored abd omen, en terostom y m ay be requ ired . Alternatively, m u ltip le
palp able loop s of bow el, a falling platelet count or one that segm ents d istal to the enterostom y m ay be p laced over a
remains 150,000 cells/ mm 3, oligu ria, neutrop enia, and feed in g tu be “stent” in h op es of p reservin g bow el length
metabolic acid osis are all relative ind ications for operation and p reventing the SBS (343). These segm ents m ay even
(337). Portal vein gas, w hich occu rs in 9% to 20% of au toanastomose. A p roxim al jeju nostom y m ay be associ-
p atients w ith N EC, and a gasless, d istend ed abd om en are ated w ith flu id m anagem ent challenges and electrolyte
harbingers of ad vanced d isease likely to requ ire op erative im balance.
intervention. Pneu m operitoneu m is a firm ind ication for Pan-involvem ent w ith necrosis of the m ajority of the
operative intervention in the setting of N EC. Up to 56% of sm all bow el occu rs in 12% of p atients and occu rs equally in
patients w ill requ ire operation at som e point d uring their both p rem atu re and fu ll-term new borns (344). Resection
cou rse (338). w ou ld be u niform ly associated w ith the d evelop m ent of
Op eration is u nd ertaken follow ing resu scitation, u su - SBS. Mortality in p atients w ith p an-involvem ent is nearly
ally in the new born ICU to avoid the hypotherm ia and 100%, esp ecially in p rematu re new borns. As su ch, m ost
d eterioration in hem od ynam ics, oxygenation, and ventila- su rgeons d o not p erform resection bu t instead choose to
tion param eters observed d u ring transp ort of the critically w ithd raw su p p ort.
ill prem atu re new born (339). It is critical to keep the new - An alternative strategy to operation in the new born
born w arm . A tense abd om en m ay requ ire d rainage p rior w ith N EC is p eritoneal d rainage (345). This involves place-
to laparotom y if it is physiologically em barrassing. Venou s m ent of a Penrose d rain u nd er local anesthesia via a 1-cm
access for p arenteral nu trition is requ ired p ostoperatively; incision p laced in the right low er qu ad rant, w hich is the
as such, central access is obtained at the tim e of the m ost likely site of p erforated N EC. Du ring d rain place-
exploratory lap arotom y. A su prau mbilical, transverse inci- m ent, the bow el is exam ined locally for viability and a
sion is created and a finger u sed to eviscerate the bow el, catheter is passed to the left upper and lower quadrants in
w hich m ay be m atted w ith ad hesions. The entire GI tract is order to irrigate the abdomen. A drain is then placed through
exam ined and areas of necrosis id entified and resected . the right low er quadrant incision toward the left side of the
Cases in w hich an isolated area of p erforation is id entified abd om en.
in the term inal ileu m m ay be treated w ith a prim ary anas- Interestingly, stu d ies su ggest that u sing this ap p roach,
tom osis. Otherw ise, an ileostom y is created d uring op era- 32% of p atients w ith p erforated N EC su rvive and requ ire
tion in alm ost all cases of N EC (89%), althou gh som e no fu rther op erations w hile 24% su ccu m b soon after
stu d ies have d em onstrated the safety of im m ed iate anasto- d rainage. Lap arotom y is requ ired w ithin 24 hou rs in 24%,
m osis even in those selected new borns w ith N EC 1000 g and op eration for d elayed strictu res becom es necessary in
in w eight (340,341). When performed , an ileostomy is cre- an ad d itional 19%. The su rvival am ong those w ith p erfo-
ated by bringing the bow el ou t throu gh either the sup raum- rated N EC ap p ears to be equ ivalent am ong those u nd er-
bilical incision or a separate 1-cm incision in the right low er going lap arotom y w hen com p ared w ith those m anaged
quad rant w hile carefully maintaining the mesenteric blood w ith p eritoneal d rainage and m ay d ep end m ore on the
supply. The former facilitates subsequent ostomy closure, u nd erlying com orbid ities than on the op erative ap p roach
w hile the latter is ad vantageous should a d ehiscence of the (346,347). Others have su ggested that p eritoneal d rainage
is m ost effective in p atients w ith isolated SIP, w h ile m ost jaund ice, the presence of excessive stoma output, failure to
p atien ts w ith N EC requ ire su bsequ en t lap arotom y (348). thrive, and d evelopm ent of a stricture at the site of the stoma
Assignm ent of p atients to SIP versu s N EC p reop eratively may ind icate early stoma closure. Stoma strictures may be
by the attend ing p ed iatric su rgeon w as confirm ed to be prevented by intermittent d ilation of the stoma opening
accu rate intraop eratively ap p roxim ately 95% of the tim e w ith a small blunt-tipped catheter.
(349). Ran d om ized con trolled trials am on g p rem atu re Recurrent N EC occu rs in approxim ately 5% of patients
infants of low birth w eight w ith p erforated N EC d em on- and can frequently be treated nonoperatively (357). Abscess
strated no d ifference in su rvival, bow el length, hosp ital d evelopment is rare in new borns, although it can occur and
stay, or m ortality follow ing abd om inal d rain p lacem ent may be d iagnosed and d rained read ily by abd om inal u ltra-
or lap arotom y (350,351). N EC, overall, is associated w ith sou nd . Mu ltip le op erations are requ ired in 55% of patients
com p rom ised neu rod evelop m ental ou tcom es (352). H ow - w ith N EC (342). Strictu res occu r in 29% of patients w ith
ever, neu rod evelop m ental m orbid ity m ay be increased in N EC, m ost comm only in those treated w ithou t laparotom y,
those p atients m anaged w ith p eritoneal d rainage w hen and are m ost often seen in the large intestine (70%) and the
com p ared w ith initial exp loratory lap arotom y (353). Cu r- term inal ileu m , w ith the sp lenic flexu re being most com -
rently, m ost p ractitioners ap p ly p eritoneal d rainage to mon (Fig. 52.23). Most p atients w ith strictu res d em onstrate
th e p rem atu re n ew born w ith p erforated N EC an d feed ing intolerance, bow el obstru ction, or H em occu lt posi-
p erform lap arotom y if p h ysiologic p aram eters d o not tive stools. A contrast enem a is u su ally d iagnostic for the
im p rove in the ensu ing 24 hou rs, althou gh the salvage most com m on large intestinal strictu res, thou gh routine
rate for lap arotom y follow ing p eritoneal d rainage is low d iagnostic contrast enem as are not recom m end ed over
(346). clinical follow -u p (358). Strictu res m ay resolve and repeat
An extraord inary and p otentially d evastating com plica- contrast stu d ies to confirm persistence of the stricture
tion of op eration for N EC is sp ontaneou s liver hem orrhage
(354). The liver in prem atu re new borns has less stromal
com p onents and is prone to laceration and bleed ing. As
such, extrem e care should be taken to avoid liver inju ry to
patients w ith N EC. If bleed ing d oes occur, packing w ith
ap p lication of hem ostatic agents and correction of coagu -
lopathy shou ld be u nd ertaken rather than attem pts at
sutu re ligation (355).
It is rare for new borns w ith enterostom ies to tolerate
fu ll feed ings unless the stom a is in the term inal ileum and
the am ou nt of bow el resected w as m inim al. Ad m inistra-
tion of Im od iu m m ay d ecrease gu t m otility, enhance the
success of feed ing, and lim it fluid and electrolyte losses.
The u rine sod iu m and seru m bicarbonate shou ld be fol-
low ed and rep leted w hen d eficient. In general, the enteros-
tom y is closed at 4 to 6 w eeks after the operation bu t
preferably not until the p rem atu re new born reaches A
ap p roxim ately 2 kg in w eight. Closure of an enterostom y
may be challenging for the surgeon becau se of the p resence
of d ense ad hesions and p hysiologically d isru p tive for the
prem atu re new born. Early closure of the ostom y ( 10
w eeks follow ing the op eration for N EC) is associated w ith
increased ventilator d ays, d ays of total parenteral nu tri-
tion, d ays requ ired to reach full oral intake, and length of
stay (356). H ow ever, d elayed closure of the ostom y
requ ires refeed ing into the d istal bow el via the m u cu s fis-
tu la and m ay p resent challenges su ch as d islod gem ent or
erosion of the refeed ing catheter, potential inju ry to the
liver from total p arental nutrition if oral intake is not fu lly
tolerated , and failu re to thrive d ue to electrolyte losses and
d ehyd ration.
Anastom otic leaks are rare but d o occu r, althou gh they
often close sp ontaneou sly given conservative m anagem ent
B
for a nu m ber of w eeks. If the new born is thriving w ith
enteral feed ings d espite the presence of an ostom y, closu re FIGURE 52.23. Strictures following necrotizing enterocolitis in the newborn
can be p ostp oned . Factors such as the onset of cholestatic in the (A) terminal ileum (arrow) and the (B) distal transverse colon (arrow).
should be consid ered (359). Because of the risk of d istal ju nction along the antim esenteric bord er (379). At birth, the
stricture, a contrast enema is performed before enterostomy expected sm all bow el length for a term infant is app roxi-
closu re in all patients. mately 240 cm w ith an ad d itional 40 cm associated w ith the
The m ortality associated w ith N EC is related to the p re- colon. By 1 year of age, the sm all bow el has grow n to an
matu rity and associated com orbid ities as w ell as com plica- estim ated 380 cm . For p reterm infants, nom ogram s for nor-
tions of the SBS (360). Overall su rvival am ong p atients w ith mal ball length are available; total length (sm all and large
N EC is 87% and is d ecreased (68%) am ong those patients bow el) increases from abou t 140 cm at 19 to 27 w eeks to
w hose w eight is 1,000 g, in those w ho have d iffuse intes- alm ost 300 cm by 35 w eeks (380). A sm all bow el length
tinal involvem ent, and in p rem atu re new borns w ith fou r or 10% of p red icted and the p resence of the ileocecal valve
more com orbid ities (30%) (340,344,347). Those p atients are associated w ith w eaning from p arenteral nu trition (PN )
w ith SIP have a higher survival rate (88%) even thou gh (381). Patients w ho w ean off PN have a 95% su rvival at
they have low er gestational age and increased incid ence of 5 years w ith or w ithou t transp lantation w hen com pared
respiratory d istress synd rom e (361). Lim ited ileal resection w ith a 52% su rvival for those w ho rem ained on PN (375).
for N EC is associated w ith a subsequent increased preva- Flu id an d electrolyte p roblem s alon g w ith m icronu tri-
lence of cholelithiasis and a risk of vitam in B12 d eficiency ent abnorm alities are u su ally p resent and treated w ith
(362). Otherw ise, lim ited ileocecal resection is not associ- m eticu lou s m onitoring of stool an d u rine ou tp u t along
ated w ith increased m orbid ity or m ortality (363). Intestinal w ith su p p lem entation of electrolyte and n u trient d efi-
p roblem s occu r in 25% of p atients over the long term and ciencies w hen p resent. Prevention of d ehyd ration is cru -
are m ostly associated w ith d evelopm ent of the SBS (344). cial to the grow th of SBS p atients. Liberal u tilization of
N eurod evelopm ent is significantly d elayed in infants agents to d ecrease gastric an d in testin al secretion and
w ith N EC su ch that 55% have severe neu rologic d eficit transit tim e is help fu l to control ostom y or stool ou tp u t.
w hen com p ared w ith 23% of non-N EC controls (364). Use of antim icrobials, as p revention for bacterial over-
Specifically, extrem ely low birth w eight ( 1000 g) infants grow th, and w eekly cycling to p revent resistance, has
w ith N EC that requ ired su rgery, d rainage or lap arotomy, also been ad vocated (377).
had low m ental d evelop m ent ind ex and p sychom otor The m ajor com p lications of SBS are related to the need
d evelop m ent ind ex scores, high rates of cerebral palsy, and for PN and p otential for bacterial overgrow th. Associated
high rates of vision im pairm ent and d eafness (353). Long- com plications inclu d e recurrent infections (catheter related
term grow th, thou gh, d oes not d iffer betw een infants w ith and otherw ise), venou s throm bosis and lack of vascular
and w ithou t N EC w hen m atched for their initial gesta- access, m alnu trition, m etabolic bone d isease, and liver fail-
tional age. u re (379). Abou t 40% to 60% of p atients on long-term IV
The best ap p roach to N EC is prevention. N EC occu rs nu trition d evelop PN -associated liver d isease (PN ALD),
m ore frequ ently in form u la-fed babies (365) and in those p resenting initially w ith cholestasis in child hood or steato-
w ith p rolonged period s w ithout feed ing w hen feed ing is sis as an ad olescent (377). Prem atu rity, d u ration of PN , and
u ltim ately initiated . In contrast, trophic feed s, feed ing w ith sep sis have all been correlated w ith faster d evelop m ent of
hu m an m ilk, the ad d ition of arginine to the d iet, and oral cholestasis (382). Measu res to p revent PN -associated
antibiotics have been show n to red u ce the incid ence of cholestasis in infancy includ e avoid ing overfeed ing by lim -
N EC (366–370). Prop hylaxis for N EC w ith antibiotics has iting total calories to 100 kcal/ kg/ d , d iscontinu ing PN 2
not becom e com m onp lace becau se of concerns for increas- to 6 hou rs each d ay and thu s allow ing cyclical GI horm one
ing antibiotic resistance. Probiotics are a prom ising concep t release, aggressively treating bacterial infections or over-
(371,372), althou gh u sing Lactobacillus has been show n to grow th, and op tim izing enteral nu trition. Intravenous fish
have an increased incid ence of sepsis (373). oil su p p lem entation m ay also d ecrease p rogression of
PN ALD (377). Om egaven (Freseniu s Kabi, Bad H om bu rg,
Germ any), an artificial om ega-3 fatty acid su p plem ent,
■ Short bowel syndrome may d ecrease p rogression of PN ALD. The p otential fatty
SBS occu rs in ap p roxim ately 1% of live births w ith d evel- acid d eficiency associated w ith Om egaven m ay be avoid ed
opm ent of liver d isease in 40% to 60% of patients and a by also ad m inistering Intralip id (Freseniu s Kabi), w hich is
mortality rate of alm ost 30% (374,375). SBS occu rs d u e to an om ega-6 fatty acid fish-oil d erivative (383).
motility d isord ers (e.g., H irschsprung d isease and pseu d o- Although the approach to SBS com m only involves p ri-
obstru ction), congenital d iseases of absorption (e.g., mary m ed ical strategies to im proving nu trition and pre-
microvillou s atrop hy), and loss of bow el (e.g., N EC, m alro- venting the com p lications ou tlined earlier, su rgical efforts
tation and m id gu t volvu lus, intestinal atresia, and gas- to increase bow el length and fu nction are p art of the m an-
troschisis) (376,377). agem ent arm am entariu m available. Most bow el-lengthen-
When assessing the potential severity of SBS, the length ing proced u res take ad vantage of the fact that the sm all
of remnant sm all bow el m u st be consid ered in conju nction bow el in the p atient w ith SBS is typ ically d ilated . In the
w ith the p resence of the ileocecal valve and length of fu nc- occasional cases w here the bow el caliber is norm al, con-
tioning colon (378). Measurem ent of the sm all intestine trolled intu ssu scep tion of the term inal ileu m into the colon
shou ld p roceed from the ligam ent of Treitz to the ileocecal may p rod u ce the requ ired sm all-bow el d ilatation (384).
FIGURE 52.24. A Bianchi procedure

separates the intestine longitudinally along
with its individual leaf of mesentery and
then reconnects them sequentially dou-
bling the initial intestinal length.
Th e Bianchi p roced u re is an intestinal length en ing Enterop exy of the sm all intestine to the exp osed
p roced u re in w h ich th e d ilated bow el is stap led lon gitu - abd om inal w all, sp ecifically the rectu s abd om inu s m u scle,
d inally w ith in th e leaves of th e m esen tery th ereby creat- is another ap p roach u sed to lengthen the sm all bow el. The
in g tw o sep arate segm en ts of bow el (Fig. 52.24). An enteropexy allow s d evelop m ent of a parasitic blood su pply
isop eristaltic an astom osis is th en p erform ed betw een th e to the loop of sm all bow el that can be u sed in su bsequ ent
tw o n ew ly created loop s of sm all bow el, th u s, effec- intestinal lengthening p roced u res (385). Stu d ies evaluating
tively, d ou blin g th e len gth . Serial tran sverse en tero- bow el-lengthening proced u res have show n that these p ro-
p lasty (STEP) is an oth er bow el-len gth en in g p roced u re in ced u res slow transit tim e and increase fat and carbohy-
w hich altern atin g m esen teric an d antim esen teric d ivid - d rate absorp tion: enteral feed s are better tolerated and
ing stap le lines are p laced p erp end icu lar to and p artially catheter infections are d ecreased (386). Com p lications fol-
across the w id th of the bow el resu lting in enhancem ent in low ing bow el-lengthening p roced u res are significant and
bow el length and red u ction in bow el caliber (Fig. 52.25) inclu d e p ostop erative bow el obstru ction and stap le line
(379). leaks, w hich often requ ire reop eration.
Med ical and su rgical op tions shou ld be m axim ized
before consid ering bow el and / or liver transplantation.
Intestinal lengthening p roced u res, su ch as the Bianchi and
STEP, can be u sed as a brid ge to transp lantation (379).
Althou gh the 1-year su rvival after intestinal transplanta-
tion is 80% to 90% and PN is costly and bu rd ensom e, the
m orbid ity of life-long imm u nosu p p ression and the 5-year
su rvival of ap p roxim ately 50% mu st be taken into account
before com m itting a patient to bow el and / or liver trans-
p lantation (374).
■ REFERENCES
1. Grosfeld JL, Rescorla FJ. Du od enal atresia and stenosis: reassessm ent
of treatm ent and outcom e based on antenatal d iagnosis, p athologic
variance, and long-term follow -u p . World J Surg 1993;17:301–309.
STEP procedure with alternating staple lines 2. H ajivassiliou CA. Intestinal obstru ction in neonatal/ p ed iatric su r-
gery. Semin Pediatr Surg 2003;12(4):241–253.
FIGURE 52.25. A Step procedure uses alternating partial staple lines to 3. Law rence MJ, Ford WD, Fu rness ME, et al. Congenital d u od enal
increase the overall surface area of the bowel and functional intestinal length obstru ction: early antenatal u ltrasou nd d iagnosis. Pediatr Surg Int
for absorption of nutrients. 2000;16:342–345.
4. Dalla Vecchia LK, Grosfeld JL, West KW, et al. Intestinal atresia and 34. Phelps S, Fisher R, Partington A, et al. Prenatal u ltrasou nd d iagnosis
stenosis: a 25-year exp erience w ith 277 cases. Arch Surg 1998;133: of gastrointestinal m alform ations. J Pediatr Surg 1997;32:438–440.
490–496; d iscu ssion 496–497. 35. Shorter N A, Georges A, Perenyi A, et al. A p rop osed classification sys-
5. Escobar MA, Lad d AP, Grosfeld JL, et al. Du od enal atresia and steno- tem for fam ilial intestinal atresia and its relevance to the und erstand -
sis: long-term follow -u p over 30 years. J Pediatr Surg 2004;39(6): ing of the etiology of jeju noileal atresia. J Pediatr Surg 2006;41(11):
867–871. 1822–1825.
6. Rothenberg SS. Laparoscop ic d u od enod u od enostom y for d uod enal 36. Zerella JT, Martin LW. Jeju nal atresia w ith absent m esentery and a hel-
obstru ction in infants and child ren. J Pediatr Surg 2002;37:1088–1089. ical ileu m . Surgery 1976;80:550–553.
7. Sou tter AD, Askew AA. Transu m bilical lap arotom y in infants: a novel 37. Miller RC. Com p licated intestinal atresias. Ann Surg 1979;189(5):
ap p roach for a w id e variety of su rgical d isease. J Pediatr Surg 2003;38: 607–611.
950–952. 38. Yam ataka A, Koga H , Shim otakahara A, et al. Lap aroscop y-assisted
8. Rescorla FJ, Grosfeld JL. Intestinal atresia and stenosis: analysis of surgery for p renatally d iagnosed sm all bow el atresia: sim p le, safe,
su rvival in 120 cases. Surgery 1985;98:668–676. and virtu ally scar free. J Pediatr Surg 2004;39(12):1815–1818.
9. Sp igland N , Yazbeck S. Com p lications associated w ith su rgical treat- 39. Thom as CG Jr. Jejunoplasty for the correction of jeju nal atresia. Surg
m ent of congenital intrinsic d u od enal obstru ction. J Pediatr Surg Gynecol Obstet 1969;129:545–546.
1990;25:1127–1130. 40. Lally KP, Chw als WJ, Weitzm an JJ, et al. H irschsp ru ng’s d isease: a
10. Arnbjornsson E, Larsson M, Finkel Y, et al. Transanastom otic feed ing possible cau se of anastom otic failu re follow ing repair of intestinal
tu be after an operation for d u od enal atresia. Eur J Pediatr Surg atresia. J Pediatr Surg 1992;27:469–470.
2002;12:159–162. 41. Tou lou kian RJ. Diagnosis and treatm ent of jeju noileal atresia. World J
11. Up ad hyay V, Sakalkale R, Parashar K, et al. Du od enal atresia: a com - Surg 1993;17:310–317.
p arison of three m od es of treatm ent. [see com m ent]. Eur J Pediatr Surg 42. Wald hau sen JH , Saw in RS. Im p roved long-term ou tcom e for p atients
1996;6:75–77. w ith jeju noileal ap ple p eel atresia. J Pediatr Surg 1997;32:1307–1309.
12. Ad zick N S, H arrison MR, d eLorim ier AA, et al. Tap ering d u od eno- 43. Lai H J, Cheng Y, Cho H , et al. Association betw een initial d isease p res-
p lasty for m egad u od enu m associated w ith d u od enal atresia. J Pediatr entation, lung d isease outcom es, and su rvival in p atients w ith cystic
Surg 1986;21:311–312. fibrosis. Am J Epidemiol 2004;159:537–546.
13. Kokkonen ML, Kalim a T, Jaaskelainen J, et al. Du od enal atresia: late 44. Murshed R, Sp itz L, Kiely E, et al. Meconiu m ileu s: a ten-year review
follow -u p. J Pediatr Surg 1988;23:216–220. of thirty-six patients. Eur J Pediatr Surg 1997;7:275–277.
14. Bax N M, Ure BM, van d er Zee DC. Lap aroscop ic d u od enod u od enos- 45. Mushtaq I, Wright VM, Drake DP, et al. Meconiu m ileu s second ary to
tom y for d u od enal atresia. Surg Endosc 2001;15(2):217. cystic fibrosis. The East Lond on exp erience. Pediatr Surg Int
15. Georgeson KE, Robertson DJ. Minimally invasive surgery in the 1998;13:365–369.
neonate: review of current evidence. Semin Perinatol 2004;28(3):212–220. 46. Rescorla FJ, Grosfeld JL, West KJ, et al. Changing p atterns of treat-
16. Seashore JH , Tou lou kian RJ. Mid gu t volvu lu s. An ever-p resent threat. m ent and su rvival in neonates w ith m econiu m ileu s. Arch Surg
Arch Pediatr Adolesc Med 1994;148:43–46. 1989;124:837–840.
17. Prasil P, Flageole H , Shaw KS, et al. Shou ld m alrotation in child ren be 47. Kao SC, Franken EA Jr. N onop erative treatm ent of sim p le m econiu m
treated d ifferently accord ing to age? J Pediatr Surg 2000;35:756–758. ileu s: a su rvey of the society for p ed iatric rad iology. Pediatr Radiol
18. Ford EG, Senac MO, Srikanth MS Jr, et al. Malrotation of the intestine 1995;25:97–100.
in child ren. Ann Surg 1992;215:172–178. 48. Fu chs JR, Langer JC. Long-term ou tcom e after neonatal m econiu m
19. Millar AJ, Rod e H , Cyw es S, et al. Malrotation and volvu lu s in infancy obstru ction. Pediatrics 1998;101:E7.
and child hood . Semin Pediatr Surg 2003;12:229–236. 49. Del Pin CA, Czyrko C, Ziegler MM, et al. Managem ent and su rvival
20. Long FR, Kram er SS, Markow itz RI, et al. Rad iograp hic p atterns of of m econiu m ileu s. A 30-year review. Ann Surg 1992;215:179–185.
intestinal m alrotation in child ren. Radiographics 1996;16:547–556; d is- 50. Jaw aheer J, Khalil B, Plu m m er T, et al. Prim ary resection and anasto-
cu ssion 556–560. m osis for com plicated m econiu m ileus: a safe proced ure? Pediatr Surg
21. Orzech N , N avarro OM, Langer JC. Is u ltrasonograp hy a good screen- Int 2007;23(11):1091–1093.
ing test for intestinal m alrotation? J Pediatr Surg 2006;41(5):1005–1009. 51. Wong KK, Lan LC, Lin SC, et al. Mu cou s fistu la refeed ing in p rem a-
22. Torres AM, Ziegler MM. Malrotation of the intestine. World J Surg ture neonates with enterostomies. J Pediatr Gastroenterol Nutr 2004;39(1):
1993;17:326–331. 43–45.
23. Severijnen R, H u lstijn-Dirkm aat I, Gord ijn B, et al. Acu te loss of the 52. Fakhou ry K, Du rie PR, Levison H , et al. Meconiu m ileu s in the
sm all bow el in a school-age boy. Difficu lt choices: to su stain life or to absence of cystic fibrosis. Arch Dis Child 1992;67:1204–1206.
stop treatm ent? Eur J Pediatr 2003;162:794–798. 53. Mishra A, Greaves R, Massie J. The relevance of sw eat testing for the
24. Wilm ore DW. Factors correlating w ith a su ccessfu l ou tcom e follow ing d iagnosis of cystic fibrosis in the genom ic era. Clin Biochem Rev
extensive intestinal resection in new born infants. J Pediatr 1972;80: 2005;26(4):135–153.
88–95. 54. Casaccia G, Tru cchi A, N ahom A, et al. The im p act of cystic fibrosis on
25. Messineo A, MacMillan JH , Pald er SB, et al. Clinical factors affecting neonatal intestinal obstruction: the need for prenatal/ neonatal
m ortality in child ren w ith m alrotation of the intestine. J Pediatr Surg screening. Pediatr Surg Int 2003;19(1/ 2):75–78.
1992;27:1343–1345. 55. Farrell PM, Kosorok MR, Rock MJ, et al. Early d iagnosis of cystic
26. Yu DC, Thiagarajan RR, Lau ssen PC. Ou tcom es after the Lad d proce- fibrosis through neonatal screening p revents severe m alnu trition and
d u re in patients w ith heterotaxy synd rom e, congenital heart d isease, im p roves long-term grow th. Wisconsin Cystic Fibrosis N eonatal
and intestinal m alrotation. J Pediatr Surg 2009;44(6):1089–1095. Screening Stu d y Grou p . Pediatrics 2001;107(1):1–13.
27. Tashjian JB, Weeks B, Bru eckner M. Ou tcom es after a Lad d p roced u re 56. Munck A, Gérard in M, Alberti C, et al. Clinical ou tcom e of cystic
for intestinal m alrotation w ith heterotaxia. J Pediatr Surg 2007;42(3): fibrosis p resenting w ith or w ithou t m econiu m ileu s: a m atched cohort
528–531. stu d y. J Pediatr Surg 2006;41(9):1556–1560.
28. van d er Zee DC, Bax N M. Lap aroscop ic rep air of acu te volvu lus in a 57. Lloyd -Still JD, Beno DW, Kim u ra RM, et al. Cystic fibrosis colonop a-
neonate w ith m alrotation. Surg Endosc 1995;9(10):1123–1124. thy. Curr Gastroenterol Rep 1999;1:231–237.
29. Gross E, Chen MK, Lobe TE. Lap aroscop ic evalu ation and treatm ent 58. Eggerm ont E. Gastrointestinal m anifestations in cystic fibrosis. Eur J
of intestinal m alrotation in infants. Surg Endosc 1996;10(9):936–937. Gastroenterol Hepatol 1996;8(8):731–738.
30. Wald hausen JH, Saw in RS. Lap aroscopic Lad d ’s proced ure and assess- 59. Chan WK, Kay SM, Laberge JM, et al. Injection sclerotherap y in the
m ent of m alrotation. J Laparoendosc Surg 1996;6(Sup pl 1):S103–S105. treatm ent of rectal prolap se in infants and child ren. J Pediatr Surg
31. Bass KD, Rothenberg SS, Chang JH . Lap aroscop ic Lad d ’s p roced u re 1998;33(2):255–258.
in infants w ith m alrotation. J Pediatr Surg 1998; 33(2):279–281. 60. Shah A, Parikh D, Jaw aheer G, et al. Persistent rectal p rolap se in chil-
32. Matzke GM, Dozois EJ, Larson DW. Su rgical m anagem ent of intes- d ren: sclerotherapy and su rgical m anagem ent. Pediatr Surg Int 2005;
tinal m alrotation in ad u lts: com parative resu lts for open and laparo- 21(4):270–273.
scopic Lad d p roced u res. J Pediatr Surg 2005;19(10):1416–1419. 61. O’Kelly TJ, Davies JR, Tam PK, et al. Abnorm alities of nitric-oxid e-
33. Palanivelu C, Rangarajan M, Shetty AR. Intestinal m alrotation w ith p rod u cing neu rons in H irschsp ru ng’s d isease: m orp hology and
m id gut volvulus presenting as acute abd om en in child ren: value of im p lications. J Pediatr Surg 1994;29:294–299; d iscu ssion 299–300.
d iagnostic and therap eu tic lap aroscop y. J Laparoendosc Adv Surg Tech 62. Red ing R, d e Ville d e Goyet J, Gosseye S, et al. H irschsp ru ng’s d isease:
A 2007;17(4):490–492. a 20-year exp erience. J Pediatr Surg 1997;32:1221–1225.
63. Polley TZ, Coran AG, Wesley JR Jr, et al. A ten-year exp erience w ith 88. Marty TL, Seo T, Su llivan JJ, et al. Rectal irrigations for the p revention
ninety-tw o cases of H irschsp ru ng’s d isease. Inclu d ing sixty-seven of p ostop erative enterocolitis in H irschsp ru ng’s d isease. J Pediatr Surg
consecu tive end orectal p u ll-throu gh p roced u res. Ann Surg 1985;202: 1995;30(5):652–654.
349–355. 89. Mu rphy F, Pu ri P. N ew insights into the p athogenesis of
64. Lew is N A, Levitt MA, Zallen GS, et al. Diagnosing H irschspru ng’s H irschspru ng’s associated enterocolitis. Pediatr Surg Int 2005;21(10):
d isease: increasing the od d s of a p ositive rectal biop sy result. J Pediatr 773–779.
Surg 2003;38:412–416; d iscu ssion 412–416. 90. H ackam DJ, Filler RM, Pearl RH , et al. Enterocolitis after the su rgical
65. Maia DM. The reliability of frozen-section d iagnosis in the pathologic treatm ent of H irschsprung’s d isease: risk factors and financial im pact.
evalu ation of H irschsp ru ng’s d isease. Am J Surg Pathol 2000;24: [see com m ent]. J Pediatr Surg 1998;33:830–833.
1675–1677. 91. Wildhaber BE, Pakarinen M, Rintala RJ, et al. Posterior myotomy/ myec-
66. Pierro A, Fasoli L, Kiely EM, et al. Staged p u ll-throu gh for rectosig- tomy for persistent stooling problems in Hirschsprung’s disease. J Pedi-
m oid H irschsp ru ng’s d isease is not safer than p rim ary p ull-throu gh. atr Surg 2004;39:920–926; discussion 920–926.
J Pediatr Surg 1997;32:505–509. 92. Langer JC, Birnbau m E. Prelim inary exp erience w ith intrasp hincteric
67. Wilcox DT, Bruce J, Bow en J, et al. One-stage neonatal p u ll-throu gh to botu linu m toxin for p ersistent constip ation after p u ll-throu gh for
treat H irschsp ru ng’s d isease. J Pediatr Surg 1997;32:243–245; d iscu s- H irschspru ng’s d isease. J Pediatr Surg 1997;32:1059–1061; d iscu ssion
sion 245–247. 1061–1062.
68. Minford JL, Ram A, Tu rnock RR, et al. Com p arison of fu nctional ou t- 93. Wester T, Rintala RJ. Early ou tcom e of transanal end orectal p u ll-
com es of Duham el and transanal end orectal coloanal anastom osis for throu gh w ith a short m u scle cu ff d u ring the neonatal p eriod . J Pediatr
H irschspru ng’s d isease. J Pediatr Surg 2004;39:161–165; d iscu ssion Surg 2004;39:157–160; d iscu ssion 157–160.
161–165. 94. Dasgu pta R, Langer JC. Evalu ation and m anagem ent of p ersistent
69. Sherm an JO, Snyd er ME, Weitzm an JJ, et al. A 40-year m u ltinational p roblem s after su rgery for H irschsp ru ng d isease in a child . J Pediatr
retrosp ective stu d y of 880 Sw enson p roced u res. J Pediatr Surg 1989;24: Gastroenterol Nutr 2008;46(1):13–19.
833–838. 95. H ad id i A. Transanal en d orectal p u ll-throu gh for H irsch sp ru n g’s
70. Moore SW, Albertyn R, Cyw es S, et al. Clinical ou tcom e and long- d isease: exp erience w ith 68 p atients. J Pediatr Surg 2003;38:1337–1340.
term quality of life after surgical correction of H irschspru ng’s d isease. 96. Blair GK, Mu rp h y JJ, Fraser GC, et al. In tern al sp h in cterotom y in
J Pediatr Surg 1996;31:1496–1502. p ost-p u ll-th rou gh H irsch sp ru n g’s d isease. J Pediatr Surg 1996;31:
71. Sop er RT, Miller FE. Mod ification of Du ham el p roced u re: elim ination 843–845.
of rectal p ou ch and colorectal sep tu m . J Pediatr Surg 1968;3:376. 97. Farru gia MK, Alexand er N , Clarke S, et al. Does transitional zone
72. Teitelbaum DH , Cilley RE, Sherm an N J, et al. A d ecad e of exp erience p u ll-through in H irschspru ng’s d isease im ply a poor p rognosis?
w ith the prim ary pull-throu gh for H irschsprung d isease in the new - J Pediatr Surg 2003;38:1766–1769.
born p eriod : a m u lticenter analysis of ou tcom es. Ann Surg 2000;232: 98. White FV, Langer JC. Circu m ferential d istribu tion of ganglion cells in
372–380. the transition zone of child ren w ith H irschsp ru ng d isease. Pediatr Dev
73. Langer JC, Fitzgerald PG, Winthrop AL, et al. One-stage versu s tw o- Pathol 2000;3:216–222.
stage Soave p ull-throu gh for H irschsprung’s d isease in the first year 99. Schm ittenbecher PP, Sacher P, Cholew a D, et al. H irschsp ru ng’s d is-
of life. J Pediatr Surg 1996;31:33–36; d iscu ssion 36–37. ease and intestinal neu ronal d ysp lasia—a frequ ent association w ith
74. Georgeson KE, Cohen RD, H ebra A, et al. Prim ary lap aroscop ic- im plications for the postop erative cou rse. Pediatr Surg Int 1999;15:
assisted en d orectal colon p u ll-throu gh for H irschsp ru ng’s d isease: 553–558.
a n ew gold stan d ard . Ann Surg 1999;229:678–682; d iscu ssion 100. Langer JC. Rep eat p u ll-throu gh su rgery for com p licated
682–683. H irschspru ng’s d isease: ind ications, techniqu es, and resu lts. J Pediatr
75. Langer JC, Du rrant AC, d e la Torre L, et al. One-stage transanal Soave Surg 1999;34:1136–1141.
pu llthrough for H irschsp ru ng d isease: a m u lticenter exp erience w ith 101. van Leeuw en K, Teitelbau m DH, Elhalaby EA, et al. Long-term follow -
141 child ren. Ann Surg 2003;238:569–583; d iscu ssion 583–585. u p of red o p u ll-throu gh p roced u res for H irschsp ru ng’s d isease: effi-
76. N asr A, Langer JC. Evolu tion of the techniqu e in the transanal p ull- cacy of the end orectal p u ll-throu gh. J Pediatr Surg 2000;35:829–833;
through for H irschsp ru ng’s d isease: effect on ou tcom e. J Pediatr Surg d iscussion 833–834.
2007;42(1):36–40. 102. Wilcox DT, Kiely EM. Rep eat p u ll-throu gh for H irschsp ru ng’s d is-
77. Davies MR, Cyw es S. Inad equ ate p ou ch em p tying follow ing Martin’s ease. J Pediatr Surg 1998;33:1507–1509.
pu ll-throu gh p roced u re for intestinal aganglionosis. J Pediatr Surg 103. Lud m an L, Sp itz L, Tsu ji H , et al. H irschsp ru ng’s d isease: fu nctional
1983;18:14–20. and p sychological follow up com paring total colonic and rectosig-
78. Ziegler MM, Royal RE, Brand t J, et al. Extend ed m yectom y–m yotom y. m oid aganglionosis. Arch Dis Child 2002;86:348–351.
A therap eutic alternative for total intestinal aganglionosis. Ann Surg 104. Teitelbaum DH , Drongow ski RA, Cham berlain JN , et al. Long-term
1993;218:504–509; d iscu ssion 509–511. stooling patterns in infants und ergoing p rim ary end orectal pull-
79. Ru ttenstock E, Pu ri P. A m eta-analysis of clinical ou tcom e in patients throu gh for H irschsp ru ng’s d isease. J Pediatr Surg 1997;32:1049–1052;
w ith total intestinal aganglionosis. Pediatr Surg Int 2009;25(10): d iscussion 1052–1053.
833–839. 105. Bai Y, Chen H , H ao J, et al. Long-term ou tcom e and qu ality of life after
80. Sauvat F, Grim ald i C, Lacaille F, et al. Intestinal transp lantation for the Sw enson p roced u re for H irschsp ru ng’s d isease. J Pediatr Surg
total intestinal aganglionosis: a series of 12 consecu tive child ren. 2002;37:639–642.
J Pediatr Surg 2008;43(10):1833–1838. 106. Martucciello G. H irschsp ru ng’s d isease, one of the m ost d ifficu lt d iag-
81. Becker L, Mashim o H . Fu rther p rom ise of stem cells therapies in the noses in ped iatric surgery: a review of the p roblem s from clinical
enteric nervou s system . Gastroenterology 2009;136(7):2055–2058. p ractice to the bench. Eur J Pediatr Surg 2008;18(3):140–149.
82. Metzger M, Cald w ell C, Barlow AJ, et al. Enteric nervou s system stem 107. Ghirard o V, Betalli P, Mognato G, et al. Lap arotom ic versu s lap aro-
cells d erived from hum an gut m ucosa for the treatm ent of aganglionic scopic Duham el pu ll-through for H irschspru ng d isease in infants and
gu t d isord ers. Gastroenterology 2009;136(7):2214–2225. child ren. J Laparoendosc Adv Surg Tech A 2007;17(1):119–123.
83. Thapar N . N ew frontiers in the treatm ent of H irschsp ru ng d isease. 108. Rü ckau er KD, von Dobschu etz E. Lap aroscop ically assisted colorectal
J Pediatr Gastroenterol Nutr 2009;48(Su p p l 2):S92–S94. resection in H irschsp ru ng’s d isease. Eur J Med Res 2005;10(8):361–365.
84. Elhalaby EA, H ashish A, Elbarbary MM, et al. Transanal one-stage 109. Craigie RJ, Conw ay SJ, Coop er L, et al. Prim ary p u ll-throu gh for
end orectal p ull-throu gh for H irschsprung’s d isease: a m ulticenter H irschsp rung’s d isease: com parison of open and laparoscopic-
stu d y. J Pediatr Surg 2004;39:345–351; d iscu ssion 345–351. assisted p roced u res. J Laparoendosc Adv Surg Tech A 2007;17(6):
85. Weber TR, Fortu na RS, Silen ML, et al. Reop eration for 809–812.
H irschspru ng’s d isease. J Pediatr Surg 1999;34:153–156; d iscu ssion 110. Sauer CJ, Langer JC, Wales PW. The versatility of the u m bilical inci-
156–157. sion in the m anagem ent of H irschsp ru ng’s d isease. J Pediatr Surg
86. Van Leeu w en K, Geiger JD, Barnett JL, et al. Stooling and m anom etric 2005;40(2):385–389.
find ings after p rim ary p u ll-throu ghs in H irschsp ru ng’s d isease: p er- 111. Singh R, Cam eron BH , Walton JM, et al. Postop erative H irschsp ru ng’s
ineal versu s abd om inal ap p roaches. J Pediatr Surg 2002;37:1321–1325. enterocolitis after m inim ally invasive Sw enson’s p roced u re. J Pediatr
87. Elhalaby EA, Coran AG, Blane CE, et al. Enterocolitis associated w ith Surg 2007;42(5):885–889.
H irschspru ng’s d isease: a clinical–rad iological characterization based 112. Liu DC, Rod rigu ez J, H ill CB, et al. Transanal m u cosectom y in the
on 168 p atients. J Pediatr Surg 1995;30:76–83. treatm ent of H irschsp ru ng’s d isease. J Pediatr Surg 2000;35(2):235–238.
113. El-Saw af MI, Drongow ski RA, Cham berlain JN , et al. Are the long- 140. Roggin KK, Breuer CK, Carr SR, et al. The u np red ictable character of
term resu lts of the transanal p u ll-throu gh equ al to those of the trans- congenital cystic lu ng lesions. J Pediatr Surg 2000;35:801–805.
abd om inal pu ll-throu gh? A com p arison of the 2 ap p roaches for 141. Tagu chi T, Su ita S, Yam anou chi T, et al. Antenatal d iagnosis and su rgi-
H irschspru ng d isease. J Pediatr Surg 2007;42(1):41–47. cal m anagem ent of congenital cystic ad enom atoid m alform ation of
114. McH ugh K, Du d ley N E, Tam P, et al. Pre-op erative MRI of anorectal the lu ng. Fetal Diagn Ther 1995;10:400–407.
anom alies in the new born p eriod . Pediatr Radiol 1995;25(Sup pl 1): 142. Morin L, Crom bleholm e TM, D’Alton ME, et al. Prenatal d iagnosis
S33–S36. and m anagem ent of fetal thoracic lesions. Semin Perinatol 1994;18:
115. Boocock GR, Donnai D. Anorectal m alform ation: fam ilial asp ects and 228–253.
associated anom alies. Arch Dis Child 1987;62:576–579. 143. Miller JA, Corteville JE, Langer JC, et al. Congenital cystic ad enom a-
116. H assink EA, Rieu PN , H am el BC, et al. Ad d itional congenital d efects toid m alform ation in the fetus: natural history and pred ictors of ou t-
in anorectal m alform ations. Eur J Pediatr 1996;155:477–482. com e. J Pediatr Surg 1996;31:805–808.
117. Rittler M, Paz JE, Castilla EE, et al. VACTERL association, ep id em io- 144. Ad zick N S, H arrison MR, Flake AW, et al. Fetal su rgery for cystic ad e-
logic d efinition and d elineation. Am J Med Genet 1996;63:529–536. nom atoid m alform ation of the lu ng. J Pediatr Surg 1993;28:806–812.
118. Tsakayannis DE, Sham berger RC. Association of im p erforate anu s 145. Atkinson JB, Ford EG, Kitagaw a H , et al. Persistent p u lm onary hyp er-
w ith occu lt sp inal d ysrap hism . J Pediatr Surg 1995;30:1010–1012. tension com p licating cystic ad enom atoid m alform ation in neonates.
119. Cortes D, Thorup JM, N ielsen OH , et al. Cryp torchid ism in boys w ith J Pediatr Surg 1992;27:54–56.
im p erforate anu s. J Pediatr Surg 1995;30:631–635. 146. van Leeu w en K, Teitelbau m DH , H irschl RB, et al. Prenatal d iagnosis
120. Adeniran JO. One-stage correction of imperforate anus and rectovestibu- of congenital cystic ad enom atoid m alform ation and its postnatal
lar fistula in girls: preliminary results. J Pediatr Surg 2002;37:E16. presentation, su rgical ind ications, and natu ral history. J Pediatr Surg
121. Georgeson KE, Inge TH , Albanese CT. Lap aroscop ically assisted 1999;34:794–798; d iscussion 798–799.
anorectal pu ll-through for high im p erforate anu s—a new techniqu e. 147. Mu rp hy JJ, Blair GK, Fraser GC, et al. Rhabd om yosarcom a arising
J Pediatr Surg 2000;35:927–930; d iscu ssion 930–931. w ithin congenital p u lm onary cysts: rep ort of three cases. J Pediatr Surg
122. Rintala RJ, Pakarinen MP. Im p erforate anu s: long- and short-term ou t- 1992;27:1364–1367.
com e. Semin Pediatr Surg 2008;17(2):79–89. 148. H asiotou M, Polyviou P, Strantzia CM, et al. Pleu rop u lm onary blas-
123. De Filipp o RE, Shau l DB, H arrison EA, et al. N eu rogenic blad d er in tom a in the area of a previou sly d iagnosed congenital lung cyst:
infants born w ith anorectal m alform ations: com parison w ith spinal report of tw o cases. Acta Radiol 2004;45:289–292.
and u rologic status. [see com m ent]. J Pediatr Surg 1999;34:825–827; 149. Coran AG, Drongow ski R. Congenital cystic d isease of the tracheo-
d iscussion 828. bronchial tree in infants and child ren. Exp erience w ith 44 consecu tive
124. And erson KD, N ew m an KD, Bond SJ, et al. Diam ond flap anoplasty cases. Arch Surg 1994;129:521–527.
in infants and child ren w ith an intractable anal strictu re. J Pediatr Surg 150. Gluer S, Scharf A, Ure BM, et al. Thoracoscop ic resection of extralobar
1994;29:1253–1257. sequ estration in a neonate. J Pediatr Surg 2002;37:1629–1631.
125. Pow ell RW, Sherm an JO, Raffensp erger JG, et al. Megarectu m : a rare 151. Becm eu r F, H orta P, Christm ann D, et al. Med iastinal stabilization by
com plication of im p erforate anu s repair and its su rgical correction by an expansion p rosthesis in postoperative congenital d iap hragm atic
end orectal pu llthrou gh. J Pediatr Surg 1982;17:786–795. hernia w ith severe p u lm onary hyp op lasia. Eur J Pediatr Surg 1995;5:
126. N ixon H H , Pu ri P. The resu lts of treatm ent of anorectal anom alies: a 295–298.
thirteen to tw enty year follow u p . J Pediatr Surg 1977;12:27–37. 152. Au d ry G, Balqu et P, Vazqu ez MP, et al. Exp and able p rosthesis in right
127. N akayam a DK, Tem pleton JM, Ziegler MM Jr, et al. Com p lications of postp neu m onectom y synd rom e in child hood and ad olescence. Ann
p osterior sagittal anorectop lasty. J Pediatr Surg 1986;21:488–492. Thorac Surg 1993;56(2):323–327.
128. Ku lshrestha S, Ku lshrestha M, Yad av A, et al. Posterior sagittal 153. Pod evin G, Larroquet M, Cam by C, et al. Postp neu m onectom y syn-
app roach for rep air of rectou rethral fistu la occu rring after perineal d rom e in child ren: ad vantages and long-term follow -u p of exp and -
su rgery for im perforated anu s at birth. J Pediatr Surg 2000;35: able p rosthesis. J Pediatr Surg 2001;36(9):1425–1427.
1155–1160. 154. H alkic N , Cuenoud PF, Corthesy ME, et al. Pu lm onary sequ estration:
129. Tsu gaw a C, H isano K, N ishijim a E, et al. Posterior sagittal anorecto- a review of 26 cases. Eur J Cardiothorac Surg 1998;14:127–133.
p lasty for failed im p erforate anu s su rgery: lessons learned from sec- 155. Tsolakis CC, Kollias VD, Panayotop ou los PP, et al. Pu lm onary sequ es-
ond ary repairs. J Pediatr Surg 2000;35:1626–1629. tration. Exp erience w ith eight consecu tive cases. Scand Cardiovasc
130. Chow d hary SK, Chalap athi G, N arasim han KL, et al. An au d it of J 1997;31:229–232.
neonatal colostom y for high anorectal m alform ation: the d eveloping 156. Conran RM, Stocker JT. Extralobar sequ estration w ith frequ ently
w orld persp ective. Pediatr Surg Int 2004;20:111–113. associated congenital cystic ad enom atoid m alform ation, typ e 2:
131. H eikkinen M, Rintala R, Lu u kkonen P, et al. Long-term anal sphincter report of 50 cases. Pediatr Dev Pathol 1999;2:454–463.
p erform ance after su rgery for H irschsp ru ng’s d isease. J Pediatr Surg 157. Bratu I, Flageole H , Chen MF, et al. The m u ltip le facets of p u lm onary
1997;32:1443–1446. sequ estration. J Pediatr Surg 2001;36:784–790.
132. Javid PJ, Barnhart DC, H irschl RB, et al. Im m ed iate and long-term 158. N obuhara KK, Gorski YC, La Qu aglia MP, et al. Bronchogenic cysts
resu lts of su rgical m anagem ent of low im perforate anu s in girls. and esop hageal d u plications: com m on origins and treatm ent. J Pediatr
J Pediatr Surg 1998;33:198–203. Surg 1997;32:1408–1413.
133. Flem ing SE, H all R, Gysler M, et al. Im p erforate anu s in fem ales: fre- 159. Kim KW, Kim WS, Cheon JE, et al. Com p lex bronchop u lm onary
qu ency of genital tract involvem ent, incid ence of associated anom - foregu t m alform ation: extralobar pulm onary sequestration associated
alies, and fu nctional ou tcom e. J Pediatr Surg 1986;21:146–150. w ith a d uplication cyst of m ixed bronchogenic and oesophageal type.
134. Bliss DP Jr, Tapp er D, And erson JM, et al. Does p osterior sagittal Pediatr Radiol 2001;31:265–268.
anorectop lasty in patients w ith high im p erforate anu s p rovid e su p e- 160. Di Lorenzo M, Collin PP, Vaillancou rt R, et al. Bronchogenic cysts.
rior fecal continence? J Pediatr Surg 1996;31:26–30; d iscu ssion 30–32. J Pediatr Surg 1989;24:988–991.
135. Ellsw orth PI, Webb H W, Cru m p JM, et al. The Malone antegrad e 161. Ribet ME, Cop in MC, Gosselin BH , et al. Bronchogenic cysts of the
colonic enem a enhances the qu ality of life in child ren u nd ergoing u ro- lu ng. Ann Thorac Surg 1996;61:1636–1640.
logical incontinence proced u res. J Urol 1996;155:1416–1418. 162. Cohen SR, Geller KA, Birns JW, et al. Foregu t cysts in infants and chil-
136. d a Silva GM, Jorge JM, Belin B, et al. N ew su rgical op tions for fecal d ren. Diagnosis and m anagem ent. Ann Otol Rhinol Laryngol 1982;91:
incontinence in p atients w ith im p erforate anu s. Dis Colon Rectum 622–627.
2004;47:204–209. 163. Yerm an H M, H olinger LD. Bronchogenic cyst w ith tracheal involve-
137. Morotti RA, Cangiarella J, Gu tierrez MC, et al. Congenital cystic ad e- m ent. Ann Otol Rhinol Laryngol 1990;99:89–93.
nom atoid m alform ation of the lung (CCAM): evalu ation of the cellu - 164. H arle CC, Dearlove O, Walker RW, et al. A bronchogenic cyst in an
lar com ponents. Hum Pathol 1999;30:618–625. infant cau sing tracheal occlu sion and card iac arrest. Anaesthesia 1999;
138. Kim WS, Lee KS, Kim IO, et al. Congenital cystic ad enom atoid m al- 54:262–265.
form ation of the lung: CT-p athologic correlation. AJR Am J Roentgenol 165. Merry C, Spurbeck W, Lobe TE, et al. Resection of foregut-d erived d upli-
1997;168:47–53. cations by minimal-access surgery. Pediatr Surg Int 1999;15:224–226.
139. Sau vat F, Michel JL, Benachi A, et al. Managem ent of asym p tom atic 166. Langer JC, H u ssain H , Khan A, et al. Prenatal d iagnosis of esop hageal
neonatal cystic ad enom atoid m alform ations. J Pediatr Surg 2003;38: atresia u sing sonography and m agnetic resonance im aging. J Pediatr
548–552. Surg 2001;36:804–807.
167. Maoate K, Myers N A, Beasley SW, et al. Gastric p erforation in infants 194. Ahm ad SA, Sylvester KG, H ebra A, et al. Esop hageal rep lacem ent
w ith oesophageal atresia and d istal tracheo-oesop hageal fistu la. Pedi- using the colon: is it a good choice? J Pediatr Surg 1996;31:1026–1030;
atr Surg Int 1999;15:24–27. d iscu ssion 1030–1031.
168. Atzori P, Iacobelli BD, Bottero S, et al. Preop erative tracheobron- 195. Ru angtrakool R, Sp itz L. Early com p lications of gastric transp osition
choscopy in new borns w ith esop hageal atresia: d oes it m atter? J Pedi- operation. J Med Assoc Thai 2000;83:352–357.
atr Surg 2006;41(6):1054–1057. 196. Dunn JC, Fonkalsrud EW, Applebaum H, et al. Reoperation after
169. Engum SA, Grosfeld JL, West KW, et al. Analysis of m orbid ity and esophageal replacement in child hood . J Pediatr Surg 1999;34:1630–1632.
m ortality in 227 cases of esop hageal atresia and / or tracheoesophageal 197. Chan KL, Saing H . Iatrogenic gastric volvu lu s d u ring transp osition
fistula over tw o d ecad es. Arch Surg 1995;130:502–508; d iscu ssion for esop hageal atresia: d iagnosis and treatm ent. J Pediatr Surg 1996;31:
508–509. 229–232.
170. Keckler SJ, St Peter SD, Valu sek PA, et al. VACTERL anom alies in 198. Sp itz L, Kiely EM, Morecroft JA, et al. Oesop hageal atresia: at-risk
p atients w ith esop h ageal atresia: an u p d ated d elineation of th e grou p s for the 1990s. J Pediatr Surg 1994;29:723–725.
sp ectru m and review of the literatu re. Pediatr Surg Int 2007;23(4): 199. Tem p leton JM Jr, Tem p leton JJ, Schnau fer L, et al. Managem ent of
309–313. esop hageal atresia and tracheoesop hageal fistu la in the neonate
171. Bow kett B, Beasley SW, Myers N A, et al. The frequ ency, significance, w ith severe resp iratory d istress synd rom e. J Pediatr Surg 1985;20(4):
and m anagem ent of a right aortic arch in association w ith esop hageal 394–397.
atresia. Pediatr Surg Int 1999;15:28–31. 200. Chavin K, Field G, Chand ler J, et al. Save the child ’s esop hagu s: m an-
172. Babu R, Pierro A, Sp itz L, et al. The m anagem ent of oesop hageal atre- agem ent of m ajor d isru p tion after rep air of esop hageal atresia. J Pedi-
sia in neonates w ith right-sid ed aortic arch. [see com m ent]. J Pediatr atr Surg 1996;31:48–51; d iscu ssion 52.
Surg 2000;35:56–58. 201. Islam S, Cavanau gh E, H oneke R, et al. Diagnosis of a p roxim al tra-
173. Chittm ittrapap S, Sp itz L, Kiely EM, et al. Anastom otic leakage fol- cheoesophageal fistula using three-d im ensional CT scan: a case
low ing su rgery for esop hageal atresia. J Pediatr Surg 1992; 27:29–32. report. J Pediatr Surg 2004;39:100–102.
174. Chittm ittrap ap S, Sp itz L, Kiely EM, et al. Anastom otic strictu re fol- 202. Gutierrez C, Barrios JE, Llu na J, et al. Recu rrent tracheoesop hageal fis-
low ing repair of esop hageal atresia. J Pediatr Surg 1990;25(5):508–511. tu la treated w ith fibrin glu e. J Pediatr Surg 1994;29:1567–1569.
175. Sp itz L. Esop hageal atresia: p ast, p resent, and fu tu re. J Pediatr Surg 203. Wheatley MJ, Coran AG, Wesley JR, et al. Efficacy of the N issen fu n-
1996;31(1):19–25. d op lication in the m anagem ent of gastroesop hageal reflu x follow ing
176. Ein SH , Shand ling B. Pu re esop hageal atresia: a 50-year review. J Pedi- esop hageal atresia rep air. J Pediatr Surg 1993;28:53–55.
atr Surg 1994;29:1208–1211. 204. Deu rloo JA, Ekkelkam p S, Bartelsm an JF, et al. Gastroesop hageal
177. Boyle EM, Irw in ED, Foker JE Jr, et al. Prim ary rep air of u ltra-long- reflu x: p revalence in ad u lts old er than 28 years after correction of
gap esophageal atresia: resu lts w ithou t a lengthening p roced u re. Ann esop hageal atresia. Ann Surg 2003;238:686–689.
Thorac Surg 1994;57:576–579. 205. Kru g E, Bergm eijer JH , Dees J, et al. Gastroesop hageal reflu x and
178. Giacom oni MA, Tresold i M, Zam ana C, et al. Circu lar m yotom y of the Barrett’s esop hagu s in ad u lts born w ith esop hageal atresia. Am J Gas-
d istal esophageal stu m p for long gap esop hageal atresia. J Pediatr Surg troenterol 1999;94:2825–2828.
2001;36:855–857. 206. Bergm eijer JH , Bou qu et J, H azebroek FW, et al. N orm al ranges of
179. Sharm a AK, Wakhlu A. Sim p le techniqu e for p roxim al pouch m obi- 24-hou r p H -m etry established in corrected esop hageal atresia. J Pedi-
lization and circu lar m yotom y in cases of esophageal atresia w ith tra- atr Gastroenterol Nutr 1999;28:162–163.
cheoesophageal fistu la. J Pediatr Surg 1994;29:1402–1403. 207. Bergm eijer JH , Tibboel D, H azebroek FW, et al. N issen fu nd op lication
180. Lai JY, Sheu JC, Chang PY, et al. Experience with d istal circular myotomy in the m anagem ent of gastroesophageal reflu x occu rring after repair
for long-gap esophageal atresia. J Pediatr Surg 1996;31:1503–1508. of esop hageal atresia. J Pediatr Surg 2000;35:573–576.
181. Kim ura K, N ishijim a E, Tsu gaw a C, et al. Mu ltistaged extrathoracic 208. Lind ahl H , Rintala R. Long-term com p lications in cases of isolated
esophageal elongation proced u re for long gap esophageal atresia: esop hageal atresia treated w ith esop hageal anastom osis. J Pediatr Surg
exp erience w ith 12 p atients. J Pediatr Surg 2001;36:1725–1727. 1995;30:1222–1223.
182. Fernand ez MS, Gu tierrez C, Ibanez V, et al. Long-gap esop hageal atre- 209. Schier F, Korn S, Michel E, et al. Exp eriences of a p arent su p p ort grou p
sia: reconstru ction preserving all portions of the esophagus by w ith the long-term consequ ences of esop hageal atresia. J Pediatr Surg
Scharli’s technique. Pediatr Surg Int 1998;14:17–20. 2001;36:605–610.
183. Evans M. App lication of Collis gastrop lasty to the m anagem ent of 210. Vazqu ez-Jim enez JF, Sachw eh JS, Liakop ou los OJ, et al. Aortop exy in
esophageal atresia. J Pediatr Surg 1995;30:1232–1235. severe tracheal instability: short-term and long-term ou tcom e in 29
184. Foker JE, Lind en BC, Boyle EM Jr, et al. Develop m ent of a tru e pri- infants and child ren. Ann Thorac Surg 2001;72:1898–1901.
m ary rep air for the fu ll sp ectru m of esop hageal atresia. Ann Surg 211. Tazuke Y, Kaw ahara H , Yagi M, et al. Use of a Palm az stent for tra-
1997;226:533–541; d iscu ssion 541–543. cheom alacia: case rep ort of an infant w ith esop hageal atresia. J Pediatr
185. Till H , Mu ensterer OJ, Rolle U, et al. Staged esop hageal lengthening Surg 1999;34:1291–1293.
w ith internal and subsequ ent external traction sutu res lead s to pri- 212. Deliu s RE, Wheatley MJ, Coran AG, et al. Etiology and m anagem ent
m ary repair of an u ltralong gap esop hageal atresia w ith u p p er p ouch of respiratory com plications after repair of esophageal atresia w ith
tracheoesophageal fistu la. J Pediatr Surg 2008;43(6):E33–E35. tracheoesop hageal fistula. Surgery 1992;112:527–532.
186. Gou gh MH . Esop hageal atresia—u se of an anterior flap in the d ifficu lt 213. Tom aselli V, Volp i ML, Dell’Agnola CA, et al. Long-term evalu ation of
anastom osis. J Pediatr Surg 1980;15:310–311. esophageal function in patients treated at birth for esop hageal atresia.
187. Brow n AK, Tam PK. Measu rem ent of gap length in esophageal atre- Pediatr Surg Int 2003;19:40–43.
sia: a sim p le p red ictor of ou tcom e. J Am Coll Surg 1996;182:41–45. 214. Dutta H K, Grover VP, Dw ived i SN , et al. Manom etric evalu ation of
188. Rescorla FJ, West KW, Scherer LR III, et al. The com p lex natu re of type postop erative patients of esop hageal atresia and tracheo-esop hageal
A (long-gap) esop hageal atresia. Surgery 1994;116:658–664. fistu la. Eur J Pediatr Surg 2001;11:371–376.
189. Pom p eo E, Coosem ans W, De Leyn P, et al. Esop hageal rep lacem ent 215. Zigm an A, Yazbeck S. Esop hageal foreign bod y obstru ction after
w ith colon in child ren u sing either the intrathoracic or retrosternal esop hageal atresia rep air. J Pediatr Surg 2002;37:776–778.
route: an analysis of both su rgical and long-term resu lts. Surg Today 216. Bax KM, van d er Zee DC. Feasibility of th oracoscop ic rep air of
1997;27:729–734. esop h ageal atresia w ith d istal fistu la. J Pediatr Surg 2002;37:
190. McCollum MO, Rangel SJ, Blair GK, et al. Prim ary reversed gastric 192–196.
tu be reconstru ction in long gap esop hageal atresia. J Pediatr Surg 2003; 217. H olcom b GW III, Rothenberg SS, Bax KM, et al. Thoracoscop ic rep air
38:957–962. of esophageal atresia and tracheoesophageal fistula: a m ulti-institu-
191. Spitz L, Kiely E, Pierro A. Gastric transp osition in child ren—a 21-year tional analysis. Ann Surg 2005;242(3):422–430.
experience. J Pediatr Surg 2004;39:276–281; d iscu ssion 276–281. 218. Lu go B, Malhotra A, Gu ner Y, et al. Thoracoscop ic versu s op en rep air
192. Khan AR, Stiff G, Moham m ed AR, et al. Esop hageal rep lacem ent w ith of tracheoesophageal fistu la and esop hageal atresia. J Laparoendosc
colon in child ren. Pediatr Surg Int 1998;13:79–83. Adv Surg Tech A 2008;18(5):753–756.
193. H irschl RB, Yard eni D, Old ham K, et al. Gastric transposition for 219. Krosnar S, Baxter A. Thoracoscop ic rep air of esop h ageal atresia
esop hageal replacem ent in child ren: exp erience w ith 41 consecu tive w ith trach eoesop hageal fistu la: anesthetic and intensive care m an-
cases w ith special em p hasis on esop hageal atresia. Ann Surg 2002;236: agem en t of a series of eigh t n eon ates. Paediatr Anaesth 2005;15(7):
531–539; d iscu ssion 539–541. 541–546.
220. Clark RH , H ard in WD, H irschl RB Jr, et al. Cu rrent su rgical m anage- 245. H arrison MR, Ad zick N S, Bu llard KM, et al. Correction of congenital
m ent of congenital d iap hragm atic hernia: a rep ort from the Congeni- d iap hragm atic hernia in u tero VII: a p rosp ective trial. J Pediatr Surg
tal Diaphragm atic H ernia Stu d y Grou p . J Pediatr Surg 1998;33: 1997;32(11):1637–1642.
1004–1009. 246. N akstad B, N aess PA, d e Lange C, et al. Com p lications of u m bilical
221. Congenital Diap hragm atic H ernia Stu d y Grou p . Defect size d eter- vein catheterization: neonatal total p arenteral nu trition ascites after
m ines survival in infants w ith congenital d iap hragm atic hernia. Pedi- su rgical rep air of congenital d iap hragm atic hernia. J Pediatr Surg 2002;
atrics 2007;120(3):e651–e657. 37:E21.
222. Extracorp oreal Life Su p p ort Organization (ELSO) Registry. The ELSO 247. Cacciari A, Ruggeri G, Mord enti M, et al. H igh-frequ ency oscillatory
Registry Rep ort. Ann Arbor, MI: Extracorp oreal Life Su p p ort Organi- ventilation versu s conventional m echanical ventilation in congenital
zation; June 30, 2009. d iap hragm atic hernia. Eur J Pediatr Surg 2001;11:3–7.
223. Iritani I. Exp erim ental stu d y on em bryogenesis of congenital 248. Azarow K, Messineo A, Pearl R, et al. Congenital d iap hragm atic her-
d iap hragm atic hernia. Anat Embryol (Berl) 1984;169:133–139. nia—a tale of tw o cities: the Toronto exp erience. J Pediatr Surg 1997;
224. H arrison MR, Jester JA, Ross N A, et al. Correction of congenital 32:395–400.
d iap hragm atic hernia in u tero. I. The m od el: intrathoracic balloon 249. The N eonatal Inhaled N itric Oxid e Stu d y Grou p (N IN OS). Anony-
p rod u ces fatal pu lm onary hyp op lasia. Surgery 1980;88:174–182. m ous inhaled nitric oxid e and hypoxic respiratory failure in infants
225. Bohn D, Tam u ra M, Perrin D, et al. Ventilatory p red ictors of p ul- w ith congenital d iap hragm atic hernia. Pediatrics 1997;99:838–845.
m onary hypoplasia in congenital d iap hragm atic hernia, confirm ed by 250. Shanley CJ, H irschl RB, Schu m acher RE, et al. Extracorp oreal life su p -
m orphologic assessm ent. J Pediatr 1987;111:423–431. port for neonatal respiratory failu re. A 20-year exp erience. Ann Surg
226. Yam ataka T, Pu ri P. Pu lm onary artery stru ctu ral changes in p u l- 1994;220:269–280; d iscu ssion 281–282.
m onary hypertension com plicating congenital d iaphragm atic hernia. 251. Schw artz SM, Verm ilion RP, H irschl RB, et al. Evalu ation of left ven-
J Pediatr Surg 1997;32:387–390. tricu lar m ass in child ren w ith left-sid ed congenital d iap hragm atic
227. Laberge JM, Flageole H . Fetal tracheal occlu sion for the treatm ent of hernia. J Pediatr 1994;125:447–451.
congenital d iap hragm atic hernia. World J Surg 2007;31(8):1577–1586. 252. H eiss KF, Clark RH , Cornish JD, et al. Preferential u se of venovenou s
228. Price MR, Galantow icz ME, Stolar CJ, et al. Con gen ital d iap h rag- extracorporeal m em brane oxygenation for congenital d iaphragm atic
m atic h ern ia, extracorp oreal m em brane oxygenation , and d eath: a hernia. Pediatr Surg 1995;30:416–419.
sp ectru m of etiologies. J Pediatr Surg 1991;26:1023–1026; d iscu ssion 253. Vazqu ez WD, Cheu H W. H em orrhagic com p lications and rep air of
1026–1027. congenital d iaphragm atic hernias: d oes tim ing of the repair m ake a
229. Dillon PW, Cilley RE, Mau ger D, et al. The relationship of p u lm onary d ifference? Data from the Extracorp oreal Life Su p p ort Organization.
artery p ressu re and su rvival in congenital d iap hragm atic hernia. J Pediatr Surg 1994;29:1002–1005; d iscu ssion 1005–1006.
J Pediatr Surg 2004;39:307–312; d iscu ssion 307–312. 254. Congenital Diap hragm atic H ernia Stu d y Grou p . Congenital
230. Manning PB, Murp hy JP, Raynor SC, et al. Congenital d iap hragm atic d iap hragm atic hernia requ iring extracorp oreal m em brane oxygena-
hernia p resenting d u e to gastrointestinal com p lications. J Pediatr Surg tion: d oes tim ing of rep air m atter? J Pediatr Surg 2009;44(6):1165–1171;
1992;27:1225–1228. d iscu ssion 1171–1172.
231. Bu rge DM, Atw ell JD, Freem an N V, et al. Could the stom ach site help 255. Wilson JM, Bow er LK, Lu nd DP, et al. Evolu tion of the techniqu e of
p red ict ou tcom e in babies w ith left sid ed congenital d iap hragm atic congenital d iap hragm atic hernia rep air on ECMO. J Pediatr Surg 1994;
hernia d iagnosed antenatally? J Pediatr Surg 1989;24:567–569. 29:1109–1112.
232. H atch EI, Kend all J, Blu m hagen J Jr, et al. Stom ach p osition as an in 256. Rozm iarek AJ, Qu reshi FG, Cassid y L, et al. Factors influ encing su r-
u tero p red ictor of neonatal ou tcom e in left-sid ed d iap hragm atic her- vival in new borns w ith congenital d iap hragm atic hernia: the relative
nia. J Pediatr Surg 1992;27:778–779. role of tim ing of surgery. J Pediatr Surg 2004;39(6):821–824.
233. Bohn DJ, Jam es I, Filler RM, et al. The relationship betw een PaCO 2 257. Reickert CA, H irschl RB, Schu m acher R, et al. Effect of very d elayed
and ventilation p aram eters in pred icting su rvival in congenital repair of congenital d iaphragm atic hernia on survival and extracor-
d iap hragm atic hernia. J Pediatr Surg 1984;19:666–671. p oreal life su p port u se. Surgery 1996;120:766–772; d iscu ssion 772–773.
234. Doné E, Gu cciard o L, Van Mieghem T, et al. Prenatal d iagnosis, pre- 258. N io M, H aase G, Kennaugh J, et al. A p rosp ective rand om ized trial of
d iction of ou tcom e and in u tero therap y of isolated congenital d elayed versu s im m ed iate rep air of congenital d iap hragm atic hernia.
d iap hragm atic hernia. Prenat Diagn 2008;28(7):581–591. J Pediatr Surg 1994;29:618–621.
235. Kitano Y, N akagaw a S, Ku rod a T, et al. Liver p osition in fetal congen- 259. d e la H u nt MN , Mad d en N , Scott JE, et al. Is d elayed su rgery really
ital d iaphragm atic hernia retains a prognostic value in the era of lu ng- better for congenital d iap hragm atic hernia?: a p rosp ective rand om -
p rotective strategy. J Pediatr Surg 2005;40(12):1827–1832. ized clinical trial. [see com m ent]. J Pediatr Surg 1996;31:1554–1556.
236. Ryp ens F, Metens T, Rocou rt N , et al. Fetal lu ng volu m e: estim ation at 260. Atkinson JB, Poon MW. ECMO and the m anagem ent of congenital
MR im aging-initial resu lts. Radiology 2001;219(1):236–241. d iap hragm atic hernia w ith large d iap hragm atic d efects requ iring a
237. Cannie MM, Jani JC, Van Kerkhove F, et al. Fetal bod y volu m e at MR p rosthetic p atch. J Pediatr Surg 1992;27:754–756.
im aging to qu antify total fetal lu ng volu m e: norm al ranges. Radiology 261. H ajer GF, vd Staak FH , d e H aan AF, et al. Recu rrent congenital
2008;247(1):197–203. d iap hragm atic hernia; w hich factors are involved ? Eur J Pediatr Surg
238. Kilian AK, Schaible T, H ofm ann V, et al. Congenital d iap hragm atic 1998;8:329–333.
hernia: pred ictive value of MRI relative lung-to-head ratio com pared 262. Tsang TM, Tam PK, Du d ley N E, et al. Diap hragm atic agenesis as a
w ith MRI fetal lu ng volu m e and sonograp hic lu ng-to-head ratio. AJR d istinct clinical entity. J Pediatr Surg 1995;30:16–18.
Am J Roentgenol 2009;192(1):153–158. 263. Scaife ER, Johnson DG, Meyers RL, et al. The sp lit abd om inal w all
239. Waag KL, Loff S, Zahn K, et al. Congenital d iap hragm atic hernia: a m u scle flap —a sim p le, m esh-free ap p roach to rep air large d iap hrag-
m od ern d ay approach. Semin Pediatr Surg 2008;17(4):244–254. m atic hernia. J Pediatr Surg 2003;38:1748–1751.
240. Yang SH , N obu hara KK, Keller RL, et al. Reliability of the lu ng-to- 264. Rana AR, Khou ri JS, Teitelbau m DH , et al. Salvaging the severe con-
head ratio as a pred ictor of outcom e in fetu ses w ith isolated left congenital d iap hragm atic hernia p atient: is a silo the solu tion? J Pediatr
genital d iap hragm atic hernia at gestation ou tsid e 24–26 w eeks. Am J Surg 2008;43(5):788–791.
Obstet Gynecol 2007;197(1):110–111; d iscu ssion e1–e5. 265. Kim AC, Bryner BS, Akay B, et al. Thoracoscop ic rep air of congenital
241. Lip shu tz GS, Albanese CT, Feld stein VA, et al. Prosp ective analysis of d iap hragm atic hernia in neonates: lessons learned . J Laparoendosc Adv
lung-to-head ratio pred icts su rvival for patients w ith prenatally d iag- Surg Tech A 2009;19(4):575–580.
nosed congenital d iap hragm atic hernia. J Pediatr Surg 1997;32(11): 266. Guner YS, Chokshi N, Arand a A, et al. Thoracoscopic repair of neonatal
1634–1636. d iaphragmatic hernia. J Laparoendosc Adv Surg Tech A 2008;18(6):875–880.
242. Ku nisaki SM, Barnew olt CE, Estroff JA, et al. Ex u tero intrap artu m 267. Yang EY, Allm end inger N , Johnson SM, et al. N eonatal thoracoscop ic
treatm ent w ith extracorp oreal m em brane oxygenation for severe con- repair of congenital d iaphragm atic hernia: selection criteria for su c-
genital d iap hragm atic hernia. J Pediatr Surg 2007;42(1):98–106. cessful ou tcom e. J Pediatr Surg 2005;40(9):1369–1375.
243. Jani JC, N icolaid es KH , Gratacós E, et al. Severe d iap hragm atic hernia 268. Arca MJ, Barnhart DC, Lelli JL Jr, et al. Early exp erience w ith m ini-
treated by fetal end oscop ic tracheal occlu sion. Ultrasound Obstet m ally invasive repair of congenital d iaphragm atic hernias: resu lts and
Gynecol 2009;34(3):304–310. lessons learned . J Pediatr Surg 2003;38:1563–1568.
244. H arrison MR, Keller RL, H aw good SB, et al. A rand om ized trial of 269. Shah SR, Wishnew J, Barsness K, et al. Minim ally invasive congenital
fetal end oscopic tracheal occlusion for severe fetal congenital d iap hragm atic hernia repair: a 7-year review of one institu tion’s exp e-
d iap hragm atic hernia. N Engl J Med 2003;349(20):1916–1924. rience. Surg Endosc 2009;23(6):1265–1271.
270. H an ekam p MN , Tjin ADGC, van H oek-Otten kam p WG, et al. Does 296. Molik KA, Gingalew ski CA, West KW, et al. Gastroschisis: a p lea for
V-A ECMO in crease th e likelih ood of ch yloth orax after con gen ital risk categorization. J Pediatr Surg 2001;36:51–55.
d iap h ragm atic h ernia rep air? J Pediatr Surg 2003;38:971–974. 297. Old ham KT, Coran AG, Drongow ski RA, et al. The d evelop m ent of
271. Gonzalez R, Bryner BS, Teitelbau m DH , et al. Chylothorax after con- necrotizing enterocolitis follow ing repair of gastroschisis: a su rpris-
genital d iap hragm atic hernia rep air. J Pediatr Surg 2009;44(6): ingly high incid ence. J Pediatr Surg 1988;23(10):945–949.
1181–1185. 298. Jayanthi S, Seym ou r P, Pu ntis JW, et al. N ecrotizing enterocolitis after
272. Graziano JN . Card iac anom alies in p atients w ith congenital d iap hrag- gastroschisis rep air: a p reventable com p lication? J Pediatr Surg 1998;
m atic hernia and their prognosis: a report from the Congenital 33(5):705–707.
Diap hragm atic H ernia Stu d y Grou p . J Pediatr Surg 2005;40(6): 299. Koivusalo A, Rintala R, Lind ahl H , et al. Gastroesop hageal reflu x in
1045–1050. child ren w ith a congenital abd om inal w all d efect. J Pediatr Surg
273. Fauza DO, Wilson JM. Congenital d iap hragm atic hernia and associ- 1999;34:1127–1129.
ated anom alies: their incid ence, id entification, and im p act on p rogno- 300. Saxena AK, H ulskam p G, Schleef J, et al. Gastroschisis: a 15-year, sin-
sis. J Pediatr Surg 1994;29:1113–1117. gle-center exp erience. Pediatr Surg Int 2002;18:420–424.
274. Bernbau m J, Schw artz IP, Gerd es M, et al. Su rvivors of extracorporeal 301. Mahou r GH , Weitzm an JJ, Rosenkrantz JG, et al. Om p halocele and
m em brane oxygenation at 1 year of age: the relationship of prim ary gastroschisis. Ann Surg 1973;177:478–482.
d iagnosis w ith health and neu rod evelop m ental sequ elae. Pediatrics 302. H eid er AL, Strau ss RA, Ku ller JA, et al. Om p halocele: clinical ou t-
1995;96:907–913. com es in cases w ith norm al karyotyp es. Am J Obstet Gynecol 2004;
275. N agaya M, Akatsu ka H , Kato J, et al. Develop m ent in lu ng function of 190:135–141.
the affected sid e after rep air of congenital d iap hragm atic hernia. 303. Greenw ood RD, Rosenthal A, N ad as AS, et al. Card iovascu lar m alfor-
J Pediatr Surg 1996;31:349–356. m ations associated w ith om p halocele. J Pediatr 1974;85:818–821.
276. D’Agostino JA, Bernbau m JC, Gerd es M, et al. Ou tcom e for infants 304. Boyd PA, Bhattacharjee A, Gou ld S, et al. Ou tcom e of p renatally d iag-
w ith congenital d iap hragm atic hernia requ iring extracorp oreal m em - nosed anterior abd om inal w all d efects. Arch Dis Child Fetal Neonatal
brane oxygenation: the first year. J Pediatr Surg 1995;30:10–15. Ed 1998;78:F209–F213.
277. Stolar CJ, Levy JP, Dillon PW, et al. Anatom ic and fu nctional abnor- 305. H ong AR, Sigalet DL, Gu ttm an FM, et al. Sequ ential sac ligation for
m alities of the esophagus in infants surviving congenital d iaphrag- giant om p halocele. J Pediatr Surg 1994;29:413–415.
m atic hernia. Am J Surg 1990;159:204–207. 306. d e Lorim ier AA, Ad zick N S, H arrison MR, et al. Am n ion inversion
278. Rescorla FJ, Shed d FJ, Grosfeld JL, et al. Anom alies of intestinal rota- in the treatm ent of gian t om p halocele. J Pediatr Surg 1991;26:
tion in child hood : analysis of 447 cases. Surgery 1990;108:710–715; 804–807.
d iscu ssion 715–716. 307. Brow n MF, Wright L. Delayed external com p ression red u ction of an
279. Lu nd DP, Mitchell J, Kharasch V, et al. Congenital d iap hragm atic her- om phalocele (DECRO): an alternative m ethod of treatm ent for m od -
nia: the hid d en m orbid ity. J Pediatr Surg 1994;29:258–262; d iscussion erate and large om phaloceles. J Pediatr Surg 1998;33:1113–1115; d iscu s-
262–264. sion 1115–1116.
280. Snyd er CL, Miller KA, Sharp RJ, et al. Managem ent of intestinal atre- 308. Barlow B, Coop er A, Gand hi R, et al. External silo red u ction of the
sia in patients w ith gastroschisis. J Pediatr Surg 2001;36:1542–1545. u nru ptu red giant om phalocele. J Pediatr Surg 1987;22:75.
281. Driver CP, Bru ce J, Bianchi A, et al. The contem p orary ou tcom e of gas- 309. H atch EI, Baxter R. Su rgical op tions in the m anagem ent of large
troschisis. J Pediatr Surg 2000;35:1719–1723. om p haloceles. Am J Surg 1987;153:449–452.
282. Lenke RR, H atch EI Jr. Fetal gastroschisis: a p relim inary rep ort ad vo- 310. Mann S, Blinm an TA, Dou glas Wilson R. Prenatal and p ostnatal m an-
cating the u se of cesarean section. Obstet Gynecol 1986;67:395–398. agem ent of om p halocele. Prenat Diagn 2008;28(7):626–632.
283. Sakala EP, Erhard LN , White JJ. Elective cesarean section im proves 311. Krasna IH . Is early fascial closu re necessary for om p halocele and gas-
ou tcom es of neonates w ith gastroschisis. Am J Obstet Gynecol 1993; troschisis? J Pediatr Surg 1995;30:23–28.
169(4):1050–1053. 312. Du nn JC, Fonkalsru d EW. Im p roved su rvival of infants w ith
284. Du nn JC, Fonkalsru d EW, Atkinson JB, et al. The influ ence of gesta- om p halocele. Am J Surg 1997;173:284–287.
tional age and m od e of d elivery on infants w ith gastroschisis. J Pediatr 313. Koivu salo A, Lind ahl H , Rintala RJ, et al. Morbid ity and qu ality of life
Surg 1999;34:1393–1395. in ad u lt p atients w ith a congenital abd om inal w all d efect: a qu estion-
285. Bethel CA, Seashore JH , Tou lou kian RJ, et al. Cesarean section d oes naire su rvey. J Pediatr Surg 2002;37:1594–1601.
n ot im p rove ou tcom e in gastroschisis. J Pediatr Surg 1989;24:1–3; 314. Koivusalo A, Taskinen S, Rintala RJ, et al. Cryp torchid ism in boys
d iscu ssion 3–4. w ith congenital abd om inal w all d efects. Pediatr Surg Int 1998;13:
286. H uang J, Ku rkchu basche AG, Carr SR, et al. Benefits of term d elivery 143–145.
in infants w ith antenatally d iagnosed gastroschisis. [see com m ent]. 315. God bole P, Sp rigg A, Dickson JA, et al. Ultrasou nd com p ared w ith
Obstet Gynecol 2002;100:695–699. clinical exam ination in infantile hyp ertrop hic p yloric stenosis. [see
287. Ad ra AM, Land y H J, N ahm ias J, et al. The fetu s w ith gastroschisis: com m ent]. Arch Dis Child 1996;75:335–337.
im p act of route of d elivery and p renatal u ltrasonograp hy. Am J Obstet 316. Kovalivker M, Erez I, Shneid er N , et al. The valu e of u ltrasou nd in the
Gynecol 1996;174(2):540–546. d iagnosis of congenital hyp ertrop hic p yloric stenosis. Clin Pediatr
288. Strauss RA, Balu R, Ku ller JA, et al. Gastroschisis: the effect of labor 1993;32:281–283.
and ru ptured m em branes on neonatal ou tcom e. Am J Obstet Gynecol 317. H aid er N , Sp icer R, Grier D, et al. Ultrasou nd d iagnosis of infantile
2003;189(6):1672–1678. hypertrophic pyloric stenosis: d eterm inants of pyloric length and the
289. Abd el-Latif ME, Bolisetty S, Abeyw ard ana S, et al. Mod e of d elivery effect of prem atu rity. Clin Radiol 2002;57:136–139.
and neonatal su rvival of infants w ith gastroschisis in Au stralia and 318. N eilson D, H ollm an AS. The u ltrasonic d iagnosis of infantile hyp er-
N ew Zealand . J Pediatr Surg 2008;43(9):1685–1690. trophic p yloric stenosis: techniqu e and accu racy. Clin Radiol 1994;49:
290. Singh SJ, Fraser A, Led itschke JF, et al. Gastroschisis: d eterm inants of 246–247.
neonatal ou tcom e. Pediatr Surg Int 2003;19:260–265. 319. Miozzari H H , Tonz M, von Vigier RO, et al. Flu id resu scitation in
291. Minkes RK, Langer JC, Mazziotti MV, et al. Rou tine insertion of a infan tile h yp ertrop hic p yloric sten osis. Acta Paediatr 2001;90:
silastic sp ring-load ed silo for infants w ith gastroschisis. [see com - 511–514.
m ent]. J Pediatr Surg 2000;35:843–846. 320. Cook-Sather SD, Tulloch H V, Liacou ras CA, et al. Gastric flu id volu m e
292. Mollitt DL, Ballantine TV, Grosfeld JL, et al. A critical assessm ent of in infants for pylorom yotom y. Can J Anaesth 1997;44:278–283.
flu id requ irem ents in gastroschisis. J Pediatr Surg 1978;13:217–219. 321. Karri V, Bou had iba N , Mathu r AB, et al. Pylorom yotom y throu gh cir-
293. Schlatter M, N orris K, Uitvlu gt N , et al. Im p roved ou tcom es in th e cum bilical incision w ith fascial extension. Pediatr Surg Int 2003;19:
treatm en t of gastrosch isis u sin g a p reform ed silo an d d elayed 695–696.
rep air ap p roach. J Pediatr Surg 2003;38:459–464; d iscu ssion 322. Cam p bell BT, McLean K, Barnhart DC, et al. A com p arison of lap aro-
459–464. scop ic and op en pylorom yotom y at a teaching hosp ital. J Pediatr Surg
294. Schw artz MZ, Tyson KR, Milliorn K, et al. Staged red u ction u sing a 37:1068–1071; d iscu ssion 1068–1071.
Silastic sac is the treatm ent of choice for large congenital abd om inal 323. Royal RE, Linz DN , Gru p p o DL, et al. Rep air of m u cosal p erforation
w all d efects. J Pediatr Surg 1983;18:713–719. d u ring pylorom yotom y: su rgeon’s choice. J Pediatr Surg 1995;30:
295. Ryckm an J, Aspirot A, Laberge JM, et al. Intestinal venou s congestion 1430–1432.
as a com plication of elective silo p lacem ent for gastroschisis. Semin 324. Sola JE, N eville H L. Lap aroscop ic vs op en p ylorom yotom y: a system -
Pediatr Surg 2009;18(2):109–112. atic review and m eta-analysis. J Pediatr Surg 2009;44(8):1631–1637.
325. Fu jim oto T, Lane GJ, Segaw a O, et al. Lap aroscop ic extram u cosal 349. Blakely ML, Lally KP, McDon ald S, et al. Postop erative ou tcom es
p ylorom yotom y versu s op en p ylorom yotom y for infantile hyp er- of extrem ely low birth -w eigh t in fan ts w ith n ecrotizin g en terocoli-
trophic pyloric stenosis: w hich is better? J Pediatr Surg 1999;34(2):3 tis or isolated intestinal p erforation: a p rosp ective cohort stu d y by
70–372. the N ICH D N eonatal Research N etw ork. Ann Surg 2005;241(6):
326. H all N J, van d er Zee J, Tan H L, et al. Meta-analysis of lap aroscop ic 984–994.
versu s op en pylorom yotom y. Ann Surg 2004;240(5):774–778. 350. Moss RL, Dim m itt RA, Barnhart DC, et al. Lap arotom y versu s p eri-
327. Cam p bell BT, McLean K, Barnhart DC, et al. A com p arison of lap aro- toneal d rainage for necrotizing enterocolitis and p erforation. N Engl J
scopic and open p ylorom yotom y at a teaching hosp ital. J Pediatr Surg Med 2006;354(21):2225–2234.
2002;37(7):1068–1071. 351. Rees CM, Eaton S, Kiely EM, et al. Peritoneal d rainage or lap arotom y
328. van d er Bilt JD, Kram er WL, van d er Zee DC, et al. Lap aroscop ic for neonatal bow el p erforation? A rand om ized controlled trial. Ann
p ylorom yotom y for hyp ertrop hic p yloric stenosis: im p act of experi- Surg 2008;248(1):44–51.
ence on the resu lts in 182 cases. Surg Endosc 2004;18(6):907–909. 352. Rees CM, Pierro A, Eaton S. N eu rod evelop m ental ou tcom es of
329. Ad ibe OO, N ichol PF, Flake AW, et al. Com p arison of ou tcom es after neonates w ith m ed ically and su rgically treated necrotizing enterocol-
laparoscopic and open pylorom yotom y at a high-volum e ped iatric itis. Arch Dis Child Fetal Neonatal Ed 2007;92(3):F193–F198.
teaching hosp ital. J Pediatr Surg 2006;41(10):1676–1678. 353. Blakely ML, Tyson JE, Lally KP, et al. Lap arotom y versu s p eritoneal
330. Pu ap ong D, Kahng D, Ko A, et al. Ad libitu m feed ing: safely im p rov- d rainage for necrotizing enterocolitis or isolated intestinal p erforation
ing the cost-effectiveness of p ylorom yotom y. J Pediatr Surg 2002;37: in extrem ely low birth w eight infants: ou tcom es throu gh 18 m onths
1667–1668. ad ju sted age. Pediatrics 2006;117(4):e680–e687.
331. Lu ciani JL, Allal H , Polliotto S, et al. Prognostic factors of the postop - 354. Vand erKolk WE, Ku rz P, Daniels J, et al. Liver hem orrhage d u ring
erative vom iting in case of hyp ertrop hic p yloric stenosis. Eur J Pediatr lap arotom y in p atients w ith necrotizing enterocolitis. J Pediatr Surg
Surg 1997;7:93–96. 1996;31:1063–1066; d iscu ssion 1066–1067.
332. Yagm u rlu A, Barnhart DC, Vernon A, et al. Com p arison of the inci- 355. Pu m berger W, Kohlhau ser C, Mayr M, et al. Severe liver haem orrhage
d ence of com p lications in op en and lap aroscop ic p ylorom yotom y: a d u ring laparotom y in very low birthw eight infants. [see com m ent].
concu rrent single institu tion series. J Pediatr Surg 2004;39:292–296; d is- Acta Paediatr 2002;91:1260–1262.
cu ssion 292–296. 356. Al-H u d haif J, Phillip s S, Gholu m S, et al. The tim ing of enterostom y
333. Yam ataka A, Tsukad a K, Yokoyam a-Law s Y, et al. Pylorom yotom y reversal after necrotizing enterocolitis. J Pediatr Surg 2009;44(5):
versu s atropine su lfate for infantile hyp ertrop hic p yloric stenosis. 924–927.
J Pediatr Surg 2000;35:338–341; d iscu ssion 342. 357. Stringer MD, Brereton RJ, Drake DP, et al. Recu rrent necrotizing ente-
334. Poon TS, Zhang AL, Cartm ill T, et al. Changing p atterns of d iagnosis rocolitis. J Pediatr Surg 1993;28:979.
and treatm ent of infantile hyp ertrop hic p yloric stenosis: a clinical 358. Born M, H olgersen LO, Sh ahrivar F, et al. Rou tin e con trast enem as
aud it of 303 patients. J Pediatr Surg 1996;31:1611–1615. for d iagnosing and m anaging strictu res follow ing nonop erative
335. Wilson R, Kan to WP, McCarthy BJ Jr, et al. Age at on set of necrotiz- treatm ent of necrotizing enterocolitis. J Pediatr Surg 1985;20(4):
ing en terocolitis: an ep id em iologic an alysis. Pediatr Res 1982;16: 461–463.
82–85. 359. Tonkin IL, Bjelland JC, H u nter TB, et al. Sp ontaneou s resolu tion of
336. Pu m berger W, Mayr M, Kohlhau ser C, et al. Sp ontaneou s localized colonic strictures cau sed by necrotizing enterocolitis: therapeutic
intestinal perforation in very-low -birth-w eight infants: a d istinct clin- im plications. AJR Am J Roentgenol 1978;130(6):1077–1081.
ical entity d ifferent from necrotizing enterocolitis. J Am Coll Surg 360. Stevenson DK, Kerner JA, Malachowski N, et al. Late morbid ity among
2002;195:796–803. survivors of necrotizing enterocolitis. Pediatrics 1980;66:925–927.
337. H u tter JJ, H athaw ay WE, Wayne ER Jr, et al. H em atologic abnorm ali- 361. Oku yam a H , Ku bota A, Ou e T, et al. A com p arison of the clinical p res-
ties in severe neonatal necrotizing enterocolitis. J Pediatr 1976;88: entation and outcom e of focal intestinal perforation and necrotizing
1026–1031. enterocolitis in very-low -birth-w eight neonates. Pediatr Surg Int
338. Bu tter A, Flageole H , Laberge JM, et al. The changing face of su rgical 2002;18:704–706.
ind ications for necrotizing enterocolitis. J Pediatr Surg 2002;37: 362. Davies BW, Abel G, Pu ntis JW, et al. Lim ited ileal resection in infancy:
496–499. the long-term consequ ences. J Pediatr Surg 1999;34:583–587.
339. Fraw ley G, Bayley G, Chond ros P, et al. Lap arotom y for necrotizing 363. Fasoli L, Tu ri RA, Sp itz L, et al. N ecrotizing enterocolitis: extent of
enterocolitis: intensive care nursery com p ared w ith operating theatre. d isease and su rgical treatm ent. J Pediatr Surg 1999;34:1096–1099.
J Paediatr Child Health 1999;35:291–295. 364. Sonntag J, Grim m er I, Scholz T, et al. Grow th and neu rod evelop m en-
340. d e Sou za JC, d a Motta UI, Ketzer CR, et al. Prognostic factors of m ortal ou tcom e of very low birthw eight infants w ith necrotizing entero-
tality in new borns w ith necrotizing enterocolitis subm itted to colitis. Acta Paediatr 2000;89:528–532.
exp loratory laparotom y. J Pediatr Surg 2001;36:482–486. 365. Lucas A, Cole TJ. Breast m ilk and neonatal necrotising enterocolitis.
341. H all N J, Curry J, Drake DP, et al. Resection and p rim ary anastom osis Lancet 1990;336(8730):1519–1523.
is a valid su rgical option for infants w ith necrotizing enterocolitis w ho 366. Schanler RJ, Lau C, H u rst N M, et al. Rand om ized trial of d onor
w eigh less than 1000 g. Arch Surg 2005;140(12):1149–1151. hum an m ilk versus preterm form ula as substitutes for m others’ ow n
342. Chw als WJ, Blakely ML, Cheng A, et al. Su rgery-associated com plica- m ilk in the feed ing of extrem ely p rem atu re infants. Pediatrics 2005;
tions in necrotizing enterocolitis: a m u ltiinstitu tional stu d y. J Pediatr 116(2):400–406.
Surg 2001;36:1722–1724. 367. McClure RJ. Trophic feed ing of the p reterm infant. Acta Paediatr Suppl
343. Lessin MS, Schw artz DL, Wesselhoeft CW Jr, et al. Mu ltip le sp onta- 2001;90(436):19–21.
neou s sm all bow el anastom osis in prem atu re infants w ith m ultiseg- 368. Am in H J, Zam ora SA, McMillan DD, et al. Arginine su p p lem entation
m ental necrotizing enterocolitis. J Pediatr Surg 2000;35:170–172. p revents necrotizing enterocolitis in the p rem atu re infant. J Pediatr
344. Chard ot C, Rochet JS, Lezeau H , et al. Su rgical necrotizing enterocoli- 2002;140(4):425–431.
tis: are intestinal lesions m ore severe in infants w ith low birth w eight? 369. Egan EA, N elson RM, Mantilla G, et al. Ad d itional exp erience w ith
J Pediatr Surg 2003;38:167–172. rou tine u se of oral kanam ycin prophylaxis for necrotizing enterocoli-
345. Ein SH , Shand ling B, Wesson D, et al. A 13-year exp erience w ith p eri- tis in infants u nd er 1,500 gram s. J Pediatr 1977;90(2):331–332.
toneal d rainage und er local anesthesia for necrotizing enterocolitis 370. Siu YK, N g PC, Fu ng SC, et al. Dou ble blind , rand om ised , p lacebo
p erforation. J Pediatr Surg 1990;25:1034–1036; d iscu ssion 1036–1037. controlled stud y of oral vancom ycin in prevention of necrotising ente-
346. Dim m itt RA, Meier AH , Skarsgard ED, et al. Salvage lap arotom y rocolitis in p reterm , very low birthw eight infants. Arch Dis Child Fetal
for failu re of p eriton eal d rain age in necrotizing enterocolitis in Neonatal Ed 1998;79(2):F105–F109.
in fants w ith extrem ely low birth w eigh t. J Pediatr Surg 2000;35: 371. Bin-N un A, Brom iker R, Wilschanski M, et al. Oral p robiotics p revent
856–859. necrotizing enterocolitis in very low birth w eight neonates. J Pediatr
347. Ehrlich PF, Sato TT, Short BL, et al. Ou tcom e of p erforated necrotizing 2005;147(2):192–196.
enterocolitis in the very low -birth w eight neonate m ay be ind epend - 372. Lin H C, Su BH , Chen AC, et al. Oral p robiotics red u ce the incid ence
ent of the typ e of su rgical treatm ent. Am Surg 2001;67:752–756. and severity of necrotizing enterocolitis in very low birth w eight
348. Cass DL, Brand t ML, Patel DL, et al. Peritoneal d rainage as d efinitive infants. Pediatrics 2005;115(1):1–4.
treatm ent for neonates w ith isolated intestinal p erforation. J Pediatr 373. Ku nz AN , Fairchok MP, N oel JM. Lactobacillu s sep sis associated w ith
Surg 2000;35:1531–1536. probiotic therap y. Pediatrics 2005;116(2):517–518.
374. Du ro D, Kam in D, Du ggan C. Overview of p ed iatric short bow el syn- 381. Sp encer AU, N eaga A, West B, et al. Ped iatric short bow el synd rom e:
d rom e. J Pediatr Gastroenterol Nutr 2008;47(Su p p l 1):S33–S36. red efining p red ictors of su ccess. Ann Surg 2005;242(3):403–409; d is-
375. N u cci A, Burns RC, Arm ah T, et al. Interd iscip linary m anagem ent of cu ssion 409–412.
p ed iatric intestinal failu re: a 10-year review of rehabilitation and 382. Btaiche IF, Khalid i N . Parenteral nu trition-associated liver com p lica-
transplantation. J Gastrointest Surg 2008;12:429–436. tions in child ren. Pharmacotherapy 2002;22(2):188–211.
376. Gou let O, Ruem m ele F. Cau ses and m anagem ent of intestinal failure 383. Diam ond IR, Sterescu A, Pencharz PB, et al. The rationale for the u se
in child ren. Gastroenterology 2006;130(2, Su p p l 1):S16–S28. of p arenteral om ega-3 lip id s in child ren w ith short bow el synd rom e
377. Ching YA, Gu ra K, Mod i B, et al. Ped iatric intestinal failu re: nu trition, and liver d isease. Pediatr Surg Int 2008;24(7):773–778.
p harm acologic, and su rgical ap p roaches. Nutr Clin Pract 2007;22:653. 384. Georgeson K, H alpin D, Figu eroa R, et al. Sequ ential intestinal length-
378. Koehler AN , Yaw orski JA, Gard ner M, et al. Coord inated interd isci- ening proced u res for refractory short bow el synd rom e. J Pediatr Surg
p linary m anagem ent of p ed iatric intestinal failu re: a 2-year review. J 1994;29(2):316–320; d iscu ssion 320–321.
Pediatr Surg 2000;35(2):380–385. 385. Ienaga T, Kim u ra K, H ashim oto K, et al. Isolated bow el segm ent
379. Su d an D, Thom p son J, Botha J, et al. Com p arison of intestinal length- (Iow a Mod el 1): techniqu e and histological stu d ies. J Pediatr Surg
ening proced ures for patients w ith short bow el synd rom e Ann Surg 1990;25(8):902–904.
2007;246(4):593–601; d iscu ssion 601–604. 386. Figu eroa-Colon R, H arris PR, Bird song E, et al. Im p act of intestinal
380. Wessel JJ, Kocoshis SA. N u tritional m anagem ent of infants w ith short lengthening on the nu tritional ou tcom e for child ren w ith short bow el
bow el synd rom e. Semin Perinatol 2007;31(2):104–111. synd rom e. J Pediatr Surg 1996;31(7):912–916.
CHAPTER
53
Surgical Complications in Children

J ames D. Geiger
■ THORACIC SURGERY su ction catheters can lead to p erforation of the p harynx or

cervical esophagus.
■ Chest infections The d iagnosis of p erforation is su sp ected if intu bation is
d ifficu lt or if excessive blood -tinged orop haryngeal secre-
The m ajority of seriou s p ed iatric chest infections are
tions are noted . An abnorm al cou rse of the nasogastric tube
treated m ed ically. H ow ever, several su ppu rative cond itions
on rad iograp hic exam ination ind icates the p resence of the
can lead to surgical complications both in d iagnosis and
p erforation. Pneu m om ed iastinu m occu rs variably. The
m anagem en t.
d iagnosis is confirm ed by esop hagram and if d elayed can
lead to sep sis. Diagnostic errors can lead to u nnecessary
Mediastinitis
thoracic exp loration. Esop hageal p erforation m ay be m is-
Acu te m ed iastinitis follow s bacterial and chem ical soiling taken for esop hageal atresia, or the inju ry m ay be m isinter-
of the m ed iastinu m by p erforation of the pharynx, trachea, p reted to be intrathoracic w hen, in fact, a cervical injury is
or esop hagu s. Perforation u su ally results from external p resent (7). Perforation into the p leu ral sp ace m ay prod u ce
trau m a, su rgery, foreign bod ies, or instru m entation (1–4). a large-tension p neu mothorax. When the d iagnosis of
Becau se the m ed iastinu m offers no anatom ic barriers to the p haryngoesop hageal p erforation is mad e qu ickly, evacu a-
spread of infection w ithin it, early d iagnosis and treatm ent tion of p neu m othoraces, antibiotics, gastric d ecom pres-
are critical to red u cing m orbid ity and m ortality. sion, and hyp eralim entation are u su ally ad equ ate therapy,
Acute med iastinitis is u su ally herald ed by a high fever, lead ing to a high rate of su rvival (8,9). Su rgical d rainage is
chest p ain, d ysp nea, cyanosis, and m arked tachycard ia and rare for these inju ries and is u su ally reserved for extensive
leu kocytosis. In neonates, acute m ed iastinitis m ay p resent extravasation or an abscess.
w ith m ore su btle signs of sepsis su ch as lethargy, tem p era-
tu re instability, and leu kopenia. Rad iographs show m ed i- Thoracic Esophageal Perforation
astinal em p hysem a, and crepitance is som etim es ap p arent
Perforation of the thoracic esop hagu s m ay follow traum a,
on p alp ation of the neck or chest w all. If the d iagnosis is
end oscop ic or d ilation p roced u res, or d isru p tion of an
d elayed and sep sis d evelop s, the m ortality rate can be sig-
esop hageal anastom osis. Most of these p erforations are
nificant, thou gh less frequ ent than in ad ults (5).
sm all contained leaks that com m only occur after d ilation of
The m anagem ent of m ed iastinitis d ep end s on the etiol-
an esop hageal strictu re and can be effectively treated non-
ogy and w hether there is ongoing contam ination or leak
op eratively. If a contrast esop hagram d em onstrates a con-
into the m ed iastinu m or pleu ral space. Drainage is essen-
tained p erforation in the m ed iastinum w ith free d rainage
tial for an abscess or continu ed contam ination from an
back into the esop hagu s, then intravenou s antibiotics and
esophageal p erforation. The m ed iastinu m can be d rained
hyp eralim entation w ith close observation are often ad e-
by a cervical, transthoracic, retrop leu ral, or anterior rou te,
qu ate therap y (1,5,10). Major p erforation of the thoracic
d ep end ing on the site of ongoing contam ination.
esop hagu s not contained w ithin the m ed iastinu m can
Cervical Esophageal Perforation som etim es be effectively treated by the placem ent of a
coated esop hageal stent (11), bu t m ay requ ire thoracotom y,
Perforations generally occur in low -birth-w eight p rem a- closu re of the p erforation site, p leu ral d rainage, and intra-
tu re infants. Typ ically, a nasogastric tu be perforates the venou s antibiotics. In som e cases, esop hageal d iversion is
hyp op harynx and cou rses along the esop hagu s u ntil it also requ ired .
enters the m ed ial p arietal pleu ra into a pleu ral space (6).
Tubes term inating in the pericard iu m and retroperitoneum Lung Abscess
have been rep orted . Less com m only, end otracheal tu bes or
Lu ng abscess is p rim arily a m ed ical d isease w ith su rgical
im p lications. There are m an y cau ses of lu n g abscess in
James D. Geiger: University of Michigan, Ann Arbor, MI ch ild ren, in clu d in g bacterial and fu n gal p n eu m on ias,
48109. cystic fibrosis (CF), foreign bod y asp iration, lu n g cysts,
746
Chapter 53 • Surgical Complications in Children 747
bronchiectasis, im m u ne d eficiencies, sequ estration, and Empyema

chronic granu lom atou s d isease. Asp iration of gastric Pleu ral effusion and empyema can complicate u p to 20% of
contents occu rs in child ren w ith neu rologic d eficits or in bacterial p neum onias. Despite ad vances in antimicrobial
p atien ts w ith abnorm al esop h ageal m otility su ch achala- therapy and the use of the pneumococcal conjugate vaccine,
sia or esop hageal atresia. This is a significant risk factor several stud ies have noted an increase in the incid ence of
for th e d evelop m en t of asp iration p n eu m onia and lu n g em p yem a as w ell as an increase in resistant organism s
abscess. (18,19). In some stud ies, methicillin-resistant staphylococ-
The initial and often only treatm ent is sp ecific antibi- cus is a frequent pathogen (20).
otics w ith p ostu ral d rainage and chest p hysiotherap y In ad d ition to antibiotics, m u ltip le treatm ent m od alities
(12,13). Whenever possible, a specific bacteriologic d iagno- exist for p leu ral effu sion and em p yem a, includ ing thora-
sis shou ld be m ad e before treatm ent. In som e cases, need le centesis, chest tu be d rainage, instillation of fibrinolytic
asp iration gu id ed by com p u ted tom ograp hy (CT), u ltra- therap y into the p leu ral cavity, and d ecortication of solid
sou nd , or bronchoscop y is help fu l in the id entification of material coating the lu ng (21,22). In the last 10 years, the
the p athogen and can also p rovid e d rainage of the abscess u se of vid eo-assisted thoracic su rgery (VATS) has d ram ati-
(14,15). Bronchoscop y w ith rem oval of an obstru cting for- cally changed the management of com plicated pneu m onia
eign bod y can be cu rative for a d istal abscess. The antibi- (23). The less invasive natu re of VATS, as w ell as the excel-
otic therap y of choice d ep end s on the resu lts of Gram stain lent p u blished resu lts, has led to the recom m end ation of an
and cu ltu re find ings. Em piric antim icrobial therap y shou ld early surgical approach to d rain the pleural space effec-
inclu d e a penicillinase-resistant agent active against Staphy- tively (Fig. 53.1) (24,25). Early intervention as opposed to a
lococcus aureus and an agent active against anaerobic bacte- step w ise ap p roach of thoracentesis follow ed by chest tu be
ria. A cou rse of at least 3 w eeks is u su ally required . Su rgical p lacem ent ap p ears to lead to excellent ou tcom es w ith sig-
intervention is reserved for the rare patient w ho d oes not nificantly shorter length of hosp italization (20,26,27). Chest
resp ond to p rolonged antibiotic therapy. This is m ore likely CT is useful for id entifying p atients w ith loculated effu-
in a p atient w ith centrally located , fu ngal or m u ltip le sions w ho are m ore likely to fail a nonsu rgical ap p roach.
abscesses, as w ell as those w ith an abscess w ithin a congen- Rarely is open thoracotom y w ith d ecortication required .
ital lu ng lesion. Thoracoscopy w ith d rainage of the abscess
has been su ccessful in som e patients (16), but in general Bronchiectasis
lobectom y is the best approach w ith the low est rate of com - Bronchiectasis is an abnorm al d ilation of the bronchi and
plications (17). In som e cases, a segm entectomy or w ed ge bronchials that is associated w ith chronic su p pu rative d is-
resection m ay be effective. End obronchial spill w ith con- ease of the airw ays (28). The d isease u su ally d evelops as a
tralateral lu ng contam ination is a p ossible and p otentially resu lt of bronchial obstru ction or of an anteced ent infection
significant com p lication of thoracotom y for lu ng abscess or su ch as p neu m onia. Bronchiectasis is more rare now than
severe p neu m onia. Use of a selective bronchial blocker, in the 1940s and 1950s w hen it ranked as one of the m ost
minim al m anip u lation of the abscess, and need le asp ira- frequ ent ind ications for p ulm onary resection in child ren
tion of the abscess once the chest is op ened m ay m inim ize (29,30). Tod ay, m ost child ren w ith bronchiectasis have
the m orbid ity associated w ith thoracotom y in these cir- an u nd erlying con gen ital p u lm onary an om aly, CF, or an
cu m stances. im m unologic d eficiency.
A B
FIGURE 53.1. A: Thoracoscopic view of fibrinous empyema. B: Atraumatic grasper (arrow) removing the fibrinous peel and breaking
down adhesions.
The p referred treatm ent for bronchiectasis is m ed ical, effective ap p roach for this grou p of p atients. In som e cases,
consisting of antibiotics, postu ral d rainage, and avoid ance oversew ing or resection of su rgical blebs is requ ired to
of inhaled toxins. Pu lm onary resection is rarely requ ired control a p ersistent air leak. Less com m only, a p u lm onary
excep t w hen the d isease is quite localized and contribu tes resection m ay be need ed .
to chronic infection w ith contam ination of the other lu ng Desp ite the ad vances in m anagem ent, CF p atients ulti-
field s (31,32). The d ecision to proceed w ith operation, esp e- m ately d evelop p rogressive resp iratory failu re. Lu ng trans-
cially in p atients w ho have CF, m ust be m ad e very carefu lly p lantation is u sefu l to correct irreversible respiratory
as it can be d ifficu lt to p red ict the benefit that lobectom y or failu re, u sing either cad averic or living lobar transplants.
segmental resection w ill provid e (31,32). The ou tcom e for lu ng transp lantation has im p roved over
tim e, w ith 5-year su rvival rates ap p roaching 70% in a num -
Cystic Fibrosis ber of series (42–44).
CF is hered itary and transm itted by a recessive gene, w hich
w as cloned and characterized in 1989 (33). There has been
d ramatic improvement in the med ical management of the
■ Respiratory foreign bodies
complications of CF. The med ian survival is now w ell over Foreign bod y asp iration is a com m on and seriou s p roblem
30 years of age comp ared w ith less than a year w hen the am ong child ren, accou nting for 7% of lethal accid ents in
d isord er w as first d escribed in 1938 (34). Progressive infec- child ren aged 1 to 3 years (45). Foreign bod y aspiration
tion and inflammation in the low er airw ays continues to m ay resu lt in either airw ay com p rom ise and d eath or seri-
lim it the length and quality of life for m ost patients w ith CF ou s sequ elae su ch as recu rrent p u lm onary infection, atelec-
and often lead s to a nu mber of pu lmonary comp lications. tasis, and bronchiectasis (46). Early d iagnosis and rem oval
Infection w ith an active host inflammatory response is pres- of the foreign bod y is critical to p reventing com plications
ent in CF airw ays from early in life. Infection is commonly (47). H ow ever, d iagnosis can be d elayed d u e to poor his-
caused by S. aureus, Haemophilus influenzae, Pseudomonas tory and nonspecific find ings on physical exam and chest
aeruginosa, and Burkholderia cepacia. Airw ay obstru ction x-ray. Lateral d ecu bitu s chest rad iograp hs can at tim es be
w ith viscous secretions is characteristic of CF and is the pri- help fu l in show ing hyp erinflation associated w ith a rad i-
mary factor in perpetuating infection and inflammation. olu cent foreign bod y. H ow ever, becau se of the risks of
The course of the lung d isease is inexorably progressive, overlooked foreign bod y asp iration, there shou ld be a low
althou gh the rate of progression is variable d epend ing on a threshold to p roceed ing w ith bronchoscopy for both d iag-
nu m ber of factors, inclu d ing genotyp e, nu tritional statu s, nosis and treatm ent (Fig. 53.2) (48).
exp osu re to environm ental toxins, exp osu re to second - Patients w ith chronic resp iratory tract foreign bod y
hand sm oke, and aerobic activity (35,36). The earliest chest retention m ay p resent w ith a recent d iagnosis of asthm a,
rad iograp hic abnorm ality is hyp erinflation, often w ith fever, hem op tysis, p neu m onia, or p u lm onary abscess. This
right u p p er lobe m u cou s retention (37). This p rogresses to grou p of p atients shou ld be consid ered for d iagnostic bron-
w id esp read bronchial d ilation, cyst, linear shad ow s, and choscop y (49). When there is a relatively low su sp icion for
infiltrates. The clinical course is marked by episod ic exacer- asp irated foreign bod y, then flexible bronchoscopy can be
bations of the pulmonary infection and inflammation treated com p leted . When there is a high su sp icion, rigid bron-
w ith antibiotic therapy, postural d rainage, and physiother- choscop y is u sefu l d u e to the broad er array of instru m ents
apy. With intense oral and often intravenou s antibiotic ther- available for the rem oval of even d ifficu lt foreign bod ies.
apy as w ell as the intense airw ay clearance therap y, the Complications of bronchoscopy are more common in
length and frequ ency of these p ulm onary exacerbations can patients w ith chronic foreign bod ies d ue to the d evelopment
be d ecreased . This in tu rn should d elay scarring and loss of of granulation tissue, stenosis, pneumonia, and bronchiecta-
pulmonary fu nction (38,39). sis. Some patients w ho have bronchoscopy w ithout identify-
Pneu m othorax occurs in 5% to 8% of patients w ith CF ing a foreign bod y may have a w orsening of their symptoms
(40). It is one of the tw o acu tely life-threatening com p lica- following the procedure due to exacerbation of an und erly-
tions of CF lu ng d isease (hem optysis is the other). Pneu - ing infectiou s p rocess. It is im p ortant that these p atients
mothorax is m ore com m on in old er p atients w ith m ore are m onitored closely in the recovery room and ad m ission
severe lu ng d isease. Patients present w ith sud d en onset of considered if there are any persistent postprocedure respira-
chest p ain and d ysp nea; how ever, both the exam and initial tory symptoms. The rigid bronchoscope provides a protec-
x-ray m ay not be very im p ressive as the stiff CF lu ng m ay tive sheath for the removal of many sharp foreign bodies.
resist collap se. Sim p le tube thoracostom y is ad equ ate treat- Pneumothorax and airw ay laceration are relatively uncom-
ment for m ost p neu m othoraces, bu t there is a high rate of mon complications (50).
recurrence. The d efinitive treatm ent, both for prom p t reso- When asp iration of p eanu ts is su sp ected , early bron-
lution and for p revention, involves ablating the p leu ral choscop y is critical for a good ou tcom e. Peanu ts that have
sp ace w ith chem ical p leu rod esis or su rgical p leu rectom y been in the airw ay for som e tim e becom e softer and an
and m anu al p leu ral abrasion (40). Ablative or su rgical inflam m atory reaction is initiated , m aking rem oval qu ite
app roaches shou ld not be w ithheld because of the potential d ifficu lt (51). Fogarty catheters and u reteral stone baskets
for futu re lu ng transp lantation (41). Thoracoscopy is an m ay facilitate rem oval of d ifficu lt foreign bod ies.
A B
FIGURE 53.2. A: Chest x-ray showing aspirated metallic foreign body in left mainstem bronchus. B: Rigid bronchoscopic view of the
foreign body obstructing the l mainstem bronchus.
■ Pectus excavatum p u lmonary compromise. Recurrence of the pectus deformity

has been reported in up to 5% of patients and appears to be
Pectu s chest d eform ities are am ong the m ost com m on more common in those w ho d o not have at least temporary
major congenital anom alies, occu rring in app roxim ately 1 internal fixation of the sternum (65). Delaying repair until at
in every 400 births (52). Pectu s excavatum is com m only least 10 years of age should minimize the extent of remodel-
recognized d u ring the first year of life. It is frequ ently ing of the chest, w hich occurs w ith grow th. Patients who
asym p tom atic u ntil ad olescent skeletal grow th occu rs, and have Marfan’s synd rom e have a higher risk of recurrence,
the d eform ity becom es m u ch m ore severe (53). There is evi- and long-term internal fixation should be considered.
d ence to ind icate that pectu s excavatu m d eform ities cau se Jeu ne’s d isease (acqu ired thoracic chond rod ystrop hy
physiologic im p airm ent and lim itations, and there is little synd rom e) is a cond ition in w hich too extensive resection
controversy that the d efects can lead to ad verse cosm etic of the costal cartilages lead s to failu re of the su bsequ ent
and p sychologic effects (54–57). chest w all grow th (65). Althou gh this can occu r at any age,
Prior to 2000, m ost surgeons p erform ed a sm all nu m ber child ren w ho und ergo pectus repair at younger ages seem
of p ectu s op erations for p ectu s excavatu m each year p ri- to be at greater risk. H yp ertrop hic scar form ation in the
marily using mod ifications of the operation p opu larized by anterior chest incision can com p rom ise an otherw ise excel-
Ravitch (58), Welch (59), H aller et al. (60), and others. With lent cosm etic resu lt. This com p lication can be prevented by
the ad vent of the N u ss proced u re first reported in 1998 (61), m inim izing trau m a to the skin flap s and antiscar measu res
the nu m ber of p ectu s op erations has significantly increased in the p ostop erative p eriod . In som e instances, excision of
becau se of the rep orted low er m orbid ity, an easier to the hyp ertrop hic scar is need ed . Other com plications,
comp lete operation, and excellent outcomes. These tw o inclu d ing a floating sternum and m igration of the subster-
ap p roaches accom p lish the p ectu s excavatu m rep air in nal fixation d evice, can occu r (66,67).
qu ite a d ifferent m anner, and althou gh stud ies su ggest that
the overall com p lication rate betw een the tw o p roced u res Complications of the Nuss Procedure
may not be significantly d ifferent (62), the pattern of com - Many p ed iatric su rgeons now rep air the m ajority of p ectu s
plications is related to the proced u re. excavatu m d efects w ith the N u ss p roced u re. This proce-
d u re, w hich is less invasive, avoid s an anterior chest inci-
Complications of Ravitch Procedure sion, cartilage resection, and sternal osteotom y by placing a
Although a number of variations of the operative technique carefu lly p reform ed , convex steel bar u nd er the sternu m
have been reported, the major concepts of (a) resection of throu gh bilateral thoracic incisions (61). Early respiratory
deformed costal cartilages w ith preservation of the peri- com p lications su ch as p neu m othorax and p leu ral effu sion
chond ral sheaths, (b) w ed ge anterior sternal osteotomy w ith ap p ear to occu r at a sim ilar rate as the Ravitch proced u re
elevation of the low er sternu m to the d esired level, and (68,69). Mod ification of the N u ss p roced u re w ith use of
(c) som e type of internal or external fixation to support the thoracoscopy to gu id e d issection of the anterior m ed i-
sternu m . Early com p lications follow ing the Ravitch p roce- astinu m and p lacem ent of the bar shou ld significantly
d u re are lim ited and generally inclu d e w ou nd infection, red u ce the risk of card iac perforation seen very early in the
p neu m othorax, and p leu ral effu sion (63,64). Most p neu - exp erience w ith this p roced u re w hen the d issection of the
m othoraces can be observed u nless there is associated m ed iastinu m w as com p leted blind ly (70). Pericard itis and
A B
FIGURE 53.3. A and B: Anterior–posterior and lateral chest x-rays demonstrate Nuss bar position and use of heavy-gauge sternal
wires around a rib for fixation.
pericard ial effu sion have been rep orted but in general d o but when complications do occur, they can lead to significant
not requ ire intervention. Wound infection occu rs in morbidity and even mortality (77). Minor complications such
roughly 2% to 3% of patients and m ay necessitate bar as gastrostomy site infections, granulation tissue, and leakage
rem oval (71). Bar d isplacem ent occu rs in 5% to 10% of occur in a significant percentage of patients and postopera-
patients, and a nu m ber of techniqu es to red uce this com p li- tive care is important to preventing these problems (78).
cation have now been d escribed (72,73). Our p reference is Location of the gastrostom y tu be on the abd om inal w all
to u se heavy gau ge sternal w ire p laced arou nd a rib to is im p ortant and requ ires p lanning. Du ring p ercu taneous
secu re the bar (Fig. 53.3). Althou gh postop erative p ain is end oscop ic gastrostom y (PEG) or laparoscop ic gastros-
significant w ith both ap p roaches necessitating ep id u ral tomy p lacem ent, it is im p ortant to m ark the costal m argin
pain m anagem ent, p atients u nd ergoing the N u ss p roce- w ith a m arking p en before insu fflation of the stom ach or
d u re requ ire longer courses of oral narcotics and in som e abd om en is initiated . If this step is not com p leted , espe-
cases the severe p ain lead s to early bar rem oval. The recu r- cially in sm all child ren, the gastrostom y tu be m ay end u p
rence rate ap p ears to be 10% and can be d ecreased by right on the costal m argin, lead ing to significant gastros-
keeping the bar in p lace for a total of 3 years (70). The ou t- tom y site com p lications and the need to be rep ositioned .
com e of patients w ith severe asym m etric d efects has been Accurate placement of the gastrostomy tube into the
less satisfactory w ith the N u ss p roced ure, requ iring either stom ach is not alw ays straight forw ard even in open surgery,
significant m od ifications or com p letion of a later Ravitch- especially in neonates w ith pure esophageal atresia w ho
type p roced u re. Other less com m on com plications inclu d e have microgastria. In ad d ition, PEG tube placement can lead
allergic reactions to the bar (74), scoliosis, second ary rib to a d evelopment of gastroenteric, m ost commonly gastro-
d eform ities d u e to the bar (75), and extraosseou s bone for- colic, fistulas in up to 3% of patients (79). Abnormal anatomy
mation (76), w hich m ay m ake bar rem oval m ore d ifficu lt. or previous surgery may contribute to this complication, and
in this group of patients, a laparoscopic or laparoscopy-
Gastric Surgery assisted approach is w arranted. The diagnosis of a gastroen-
Gastrostomy. Gastrostomy is a procedure used frequently in teric fistula follow ing a PEG can be d ifficult and is often
the care of pediatric surgical patients. Depending on the clin- d elayed (80). This problem often becomes apparent at the
ical variables, gastrostom y tube p lacem ent can be accom - time of the first gastrostomy tube change.
plished with an open laparotomy, percutaneous endoscopic A com mon com p lication of gastrostom y is inad vertent
approach, or a laparoscopic approach. As the indications for rem oval by either the p atient or the treating m ed ical p er-
placement of gastrostomy tubes have broadened, the proce- sonnel. If the tu be w as p laced w ith an op en or lap aroscopic
dure is being completed on patients with significant comor- ap p roach that inclu d ed tacking su tu res of the stom ach to
bidities. Despite this, the complication rate overall is fairly low, the p osterior fascia, then rep lacem ent of the tu be by an
app rop riately trained m ed ical practitioner m ay be p ossi- d eath (88). Med ical treatm ent of GERD has trad itionally
ble, bu t correct tu be placem ent shou ld be confirm ed w ith a involved ad m inistration of antisecretory and p rokinetic
contrast stu d y. In PEG placem ent, early d islod gem ent w ill agents (89). Proton pump inhibitors, w idely used in children
requ ire a red o PEG if recognized p rom p tly or p otentially a for the past few years, are effective in treating esophagitis.
laparoscopic or open proced u re if significant abd om inal The loss of the use of cisaprid e has significantly d epleted the
contam ination has occu rred . In chronically placed gastros- arm am entariu m of p rokinetic agents. Therefore, the m an-
tom y tu bes, fam ily m em bers and caregivers can be trained agem ent of other com p lications of reflu x, inclu d ing pu l-
in tu be rep lacem ent. This shou ld be d one rapid ly becau se m on ary asp iration of gastric con ten ts (w ith su bsequ ent
the gastrostom y stom a can close quickly. At the very least, a p n eu m onia and reactive airw ay d isease), ap p aren t life-
sm aller tu be su ch as a Foley catheter can be p laced u ntil a threatening events, and failu re to thrive, m ay necessitate
new gastrostom y tu be can be inserted . antireflux surgery.
In som e p atients, significant leakage from the gastros- The d evelop m ent of m inim ally invasive (lap aroscop ic)
tom y site lead ing to enlargem ent of the gastrostom y fu nd op lication increased the nu m ber of referrals for antire-
w ou nd and p rolapse of gastric m ucosa can occu r. Delayed flu x su rgery, at least initially (90). Fu nd op lication rem ains
gastric em ptying and increased intra-abd om inal pressu re, one of the three m ost com m on m ajor su rgical p roced u res
as can occu r in patients w ith cerebral p alsy w ith severe p erform ed in infants and child ren by p ed iatric surgeons in
spasticity or p atients w ith respiratory failu re, increases the the United States. In m any stu d ies, fu nd op lication has been
risk of this com p lication (78). In many p atients, this can be show n to be highly effective in p reventing reflux, em esis,
managed by d iscontinu ation of the gastrostom y tube for at and m any of the com p lications associated w ith GERD.
least 24 hou rs to allow the stom a to close partially. A larger H ow ever, becau se of the alteration of the gastroesop hageal
balloon catheter m ay also be of help in sealing the leak and anatom y and fu nction, antireflu x su rgery m ay lead to a
allow ing the site to heal. A nu mber of topical agents m ay variety of sid e effects or comp lications. The N issen fu nd o-
assist in p rotecting the skin and stim ulating healing of the p lication, either lap aroscop ic or op en, is the m ost comm on
site. In d ifficu lt cases, the gastrostom y tube can be con- p roced u re, bu t som e su rgeons p refer p artial fu nd op lication
verted to a gastrojeju nal feed ing tube, and if this is u nsu c- su ch as the Thal fu nd op lication. In all p roced ures, fund o-
cessfu l, then this site can be su rgically revised (81). p lication is d esigned to p revent GER by correcting hiatal
herniation, lengthening the intra-abd om inal p ortion of the
esop hagu s, tightening the cru ra, and increasing the pres-
■ Gastrocutaneous fistula su re at the level of the low er esop hageal sp hincter. Fund o-
When a p atient no longer requires a gastrostom y, the tu be p lication is su ccessfu l in abolishing GERD symp tom s in
is d iscontinu ed . Closure of the gastrostom y site occu rs 80% to 90% of p atients in long-term follow -u p stud ies (91).
spontaneou sly in the m ajority of patients. In 20% to 40% of H ow ever, both short- and long-term com p lications occu r
patients, a p ersistent gastrocutaneou s fistu la d evelop s and can at tim es be very d ifficu lt to m anage.
(82–84). The m ost im portant factor pred isposing to the p er- Im m ed iate com plications of a prim ary laparoscopic fun-
sistence of a gastrocu taneou s fistu la ap p ears to be the d oplication should be very rare events. In general, patients
length of tim e the tu be w as in place before rem oval (85). und ergoing N issen fund oplication have a short length of
Local m easures such as cau tery of the epithelialized track, stay often 48 hou rs.
occlu sive w ou nd d ressings, and installation of fibrin glu e Failure of fund oplication to improve preoperative symp-
may facilitate closu re of a gastrocu taneous fistula in som e toms may be caused by erroneous d iagnosis of GERD. Con-
patients (86). A significant p ercentage of patients w ith a d itions commonly mimicking GERD and associated w ith a
persistent gastrocu taneous fistula requ ire surgical closu re, high incid ence of problems after surgery includ e cyclic vom-
w hich can be accom p lished as an ou tp atient p roced u re. iting, rumination, gastroparesis, and eosinophilic esophagi-
The gastrocu taneou s fistu la is m obilized , and the stom ach tis. It is critical that these cond itions are consid ered before
is closed and physically separated from the facial closure. su rgery (92).
Sid e effects d irectly related to antireflu x su rgery inclu d e
d ysp hagia d u e to a tight fu nd op lication, herniation of the
■ Fundoplication w rap throu gh the hiatu s, d evelop m ent of a p eriesophageal
Gastroesophageal reflux disease (GERD) is a relatively hernia, or a sm all-bow el obstru ction from ad hesions (93).
benign cond ition in the you nger infant. Most p atients There is an early exp erience w ith end oscop ic, end olu m inal
improve, at least symptomatically, during the first 18 months fu nd op lication for GERD, bu t lon g-term d ata w ill be
of life. In old er children and adults, GERD is often a chronic requ ired to com p are com p lications and ou tcom es (94).
disease, unlikely to resolve spontaneously. Some child ren,
such as those with neurologic disorders or chronic pulmonary
disease, are at particular risk for complications of poorly
■ Dysphagia
controlled GERD. In fact, in som e p atien ts, GERD m ay be Dysphagia is a common problem especially in the early post-
the p rim ary agent ind u cing resp iratory d isease su ch as operative period (95). This is especially true in the todd ler age
asthma (87). In some infants, it may be a cause of sudd en group who often take longer to adjust to the fundoplication.
This early d ysphagia, which is most likely made w orse by probably not the best ind ication for a d rainage proced ure,
the ed ema and inflam mation associated w ith the norm al and u se of solid p hase emptying maybe more help ful. The
healing p rocess, resolves over the first few m onths in the treatment of gas-bloat symptoms is challenging, and there
vast majority of patients. In 15% of patients, d ysphagia is are no controlled stu d ies evalu ating the d ifferent p harmaco-
persistent due to a tight fundoplication or overzealous clo- logical interventions available to treat these sym ptom s. Pro-
sure of the hiatus. In this group, esophageal d ilation m ay kinetic agents such as metoclopramid e, erythromycin, and
improve symptoms dramatically without compromising the octreotid e have been used to treat gas-bloat symptoms.
fund oplication. The d ilation should not be performed before Metoclopram

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Complications in Surgery 2nd Ed

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Com p lications

Michael W. Mulholland, MD, PhD

© 2011 by LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER business

First Edition © 2006 by Lippincott Williams & Wilkins

Library of Congress Cataloging-in-Publication Data

Sanjeev Aggarwal, MD Andrew C. Chang, MD Matthew J . Eagleton, MD

Samir K. Gadepalli, MD, MBA Ronald B. Hirschl, MD Christine L. Lau, MD

Marc R. Moon, MD J ohn E. Rectenwald, MD Randall S. Sung, MD

Contributors v 20. Abnorm alities in Coagu lation . . . . . . . . . . . . . . . . 200

1. Su rgical Com plications . . . . . . . . . . . . . . . . . . . . . . . . 3 P ART I I I :

38. Com p lications of Append ectom y and P A R T VI I :

Surgical Training: Present and Future

■ INTRODUCTION trend . The p resent-d ay grad u ating su rgical resid ent is

Table 3 .2 Percen t a ge of op en su r gica l r esid en cy slot s ﬁ lled a,b

FIGURE 3.1. Simulators are avail-

FIGURE 3.2. Simulated environ-

Table 4 .2 Typ es of CM E a ct ivit ies a n d t h eir ch a r a ct er ist ics

■ INTRODUCTION 6. organ transp lantation

■ DENIAL OF PRIVILEGES ■ REFERENCES

FIGURE 6.1. Big problems with small 100%

FIGURE 6.2. Risk-adjusted mortality rates for coro- 20

Coronary artery bypass FIGURE 6.3. Variation in risk-adjusted mortal-

Quintiles of Hospital Mortality

In con trast, th e im p ortan ce of risk ad ju stm en t m ay 50

Process: Patient selection & Procedure/ Prevention of Recognition &

Outcomes: No complication Seminal Downstream Death

FIGURE 6.6. Rates of mortality, major Colectomy

■ INTRODUCTION ■ SELECTIVE REFERRAL

Table 7 .1 Ch a ra ct er ist ics of t h r ee d iffer en t m od els for r ed u cin g va r ia t ion a n d im p rovin g

effectiveness in m arked ly red ucing rates of blood stream

FIGURE 7.2. Relationship of hospital process compliance to 10.0

Ris k-a djus te d morta lity ra te (%)

Ho s pitals ranke d o n pro c e s s c o mplianc e

for hosp ital ad m inistration w hen negotiating w ith insu r-

Table 8 .1 Th e ﬁ n a n cia l im p lica t ion s of su r gica l com p lica t ion s follow in g

4% Unlike m any national initiatives, the collegial atm os-

Colle gia lity is high 100%

BCBS M is a re lia ble

Fina ncia l s upport

Us e d for compe titive

Re lucta nt to dis cus s

FIGURE 9.1. Systems failures (Reproduced with per- S ys te ms Failure s

S e rio us e rro rs are fre que ntly the re s ult o f

Vo lu n ta ry re p o rtin g include s “ne a r-mis s e s ” a s we ll a s eve nts tha t re s ult in pa tie nt ha rm

% o f re s po nde nts in e ac h nurs ing unit re s po nding with

70% 68% 68% 68%

Teamwork climate across Michigan ICUs (Repro-

No BSI 21% No BSI 31% No BSI 44%

FIGURE 9.6. Venilator-associated pneumonia—UH ICUs 10.00

Rate per 1,000 Ventilator Days

Table 9 .2 Un iver sit y of M ich iga n p r ot ocol for

Table 9 .6 Wor ld H ea lt h O r ga n iza t ion (W H O ) su r gica l sa fet y ch eck list

SIGN IN TIME OUT SIGN OUT

■ INTRODUCTION lem s, and the severity of d isease is u sed to m od ify its

Table 1 0 .2 Ca rdiac risk a stratiﬁ ca tion for ■ Diagnostic testing

Pe riope ra tive s urve illa nce

Active ca rdia c Eva lua te a nd tre a t pe r Cons ide r

Good functiona l ca pa city (MET leve l

Table 1 0 .4 G u id e t o n on in va sive t est in g in p r eop era t ive p a t ien t s

Table 1 0 .6 Recom m en d a t ion s for bet a -block er m ed ica l t h era py

Table 1 1 .3 Com m on p r escr ip t ion m ed ica t ion s t h a t m ay r eq u ir e sp ecia l

Table 1 1 .4 Pot en t ia l in t er a ct ion s for som e com m on h er ba l m ed icin es

Table 1 1 .5 Su ggest ion s for a d u lt p r eop era t ive t est in g

Fluid or Lyte Loss