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Jean-Louis Vincent
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TEXTBOOK OF
CRITICAL CARE
7
th E d i t i o n
Downloaded from ClinicalKey.com at UCSI University January 11, 2017.

For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
TEXTBOOK OF
CRITICAL CARE
7 TH E D I T I O N
JEAN-LOUIS VINCENT, MD, PhD PATRICK M. KOCHANEK, MD, MCCM

Professor of Intensive Care Medicine Ake N. Grenvik Professor in Critical Care Medicine
Université Libre de Bruxelles Professor and Vice Chairman
Department of Intensive Care Department of Critical Care Medicine
Erasme University Hospital Professor of Anesthesiology, Pediatrics, Bioengineering,
Brussels, Belgium and Clinical and Translational Science
University of Pittsburgh School of Medicine
EDWARD ABRAHAM, MD Director, Safar Center for Resuscitation Research
Professor and Dean Pittsburgh, Pennsylvania
Wake Forest School of Medicine
Winston-Salem, North Carolina MITCHELL P. FINK, MD†
Professor of Surgery and Anesthesiology
FREDERICK A. MOORE, MD, MCCM Vice Chair for Critical Care
Professor of Surgery Department of Surgery
Head, Acute Care Surgery David Geffen School of Medicine at UCLA
Department of Surgery Los Angeles, California
University of Florida College of Medicine
Gainesville, Florida †Deceased.

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TEXTBOOK OF CRITICAL CARE, SEVENTH EDITION ISBN: 978-0-323-37638-9
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Previous editions copyrighted 2011, 2005, 2000, 1995, 1989, 1984.
Library of Congress Cataloging-in-Publication Data
Names: Fink, M. P. (Mitchell P.), 1948- , editor. | Vincent, J. L., editor. | Abraham, Edward, editor. |
Moore, Frederick A., 1953- , editor. | Kochanek, Patrick, 1954- , editor.
Title: Textbook of critical care / editors, Mitchell P. Fink, Jean-Louis Vincent, Edward Abraham, Frederick A.
Moore, Patrick M. Kochanek.
Description: 7/E. | Philadelphia, PA : Elsevier, [2017] | Preceded by Textbook of critical care / [edited by]
Jean-Louis Vincent … [et al.]. 6th ed. c2011. | Includes bibliographical references and index.
Identifiers: LCCN 2015048565 | ISBN 9780323376389 (hardcover : alk. paper)
Subjects: | MESH: Critical Care | Intensive Care Units
Classification: LCC RC86.7 | NLM WX 218 | DDC 616.02/8—dc23 LC record available at http://lccn.loc.
gov/2015048565
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BOOK
Textbook of Critical Care, Seventh Edition

Table of Contents
Front Matter 21. Thrombocytopenia Weakness
Copyright 22. Coagulopathy in the ICU 47. Advanced Bedside

23. Jaundice Neuromonitoring
Dedications
24. Gastrointestinal Bleeding 48. Coma
In Memoriam
25. Ascites 49. Use of Brain Injury Biomarkers
Contributors in Critical Care Settings
26. Acute Abdominal Pain
Preface 50. Cardiopulmonary Cerebral
27. Ileus
Resuscitation
28. Diarrhea
51. Delirium
1. Sudden Deterioration in 29. Rash and Fever
Neurologic Status 52. Management of Acute Ischemic
30. Chest Pain Stroke
2. Agitation and Delirium
31. Biochemical or 53. Nontraumatic Intracerebral and
3. Management of Acute Pain in Electrocardiographic Evidence Subarachnoid Hemorrhage
the Intensive Care Unit of Acute Myocardial Injury
54. Seizures in the Critically Ill
4. Fever 32. Point-of-Care Ultrasound
55. Neuromuscular Disorders in the
5. Very High Systemic Arterial 33. Echocardiography Critically Ill
Blood Pressure
34. Cardiovascular Monitoring 56. Traumatic Brain Injury
6. Low Systemic Arterial Blood
35. Bedside Monitoring of 57. Spinal Cord Injury
Pressure
Pulmonary Function
7. Tachycardia and Bradycardia 58. Neuroimaging
36. Arterial Blood Gas
8. Arterial Hypoxemia 59. Intensive Care After
Interpretation
Neurosurgery
9. Acute Respiratory Failure 37. Tracheal Intubation
60. Key Issues in Pediatric
10. Pulmonary Edema 38. Tracheostomy Neurointensive Care
11. Polyuria 39. Mechanical Ventilation 61. Patient-Ventilator Interaction
12. Oliguria 40. Renal Replacement Therapy 62. Noninvasive Positive-Pressure
13. Hypernatremia and 41. Targeted Temperature Ventilation
Hyponatremia Management and Therapeutic 63. Weaning from Mechanical
14. Hyperkalemia and Hypokalemia Hypothermia Ventilation
15. Hyperphosphatemia and 42. Extracorporeal Membrane 64. Adjunctive Respiratory Therapy
Hypophosphatemia Oxygenation (Venovenous and
65. Hyperbaric Oxygen in Critical
16. Hypomagnesemia Venoarterial ECMO)
Care
17. Hypocalcemia and 43. Nutritional Support in Adults
66. Imaging of the Chest
Hypercalcemia 44. Nutritional Support in Children
67. Acute Respiratory Distress
18. Hypoglycemia 45. Early Ambulation in the ICU Syndrome
19. Hyperglycemia 46. Role of Early Mobilization in the 68. Aspiration Pneumonitis and
20. Anemia Prevention of ICU-Acquired Pneumonia
69. Severe Asthma Exacerbation Cholecystitis System Failure in Children
70. Chronic Obstructive Pulmonary 98. Acute Pancreatitis 123. Infections of the Urogenital
Disease 99. Peritonitis and Intraabdominal Tract
71. Pulmonary Embolism Infection 124. Central Nervous System
72. Pulmonary Hypertension 100. Ileus and Mechanical Bowel Infections
73. Pneumothorax Obstruction 125. Infections of Skin, Muscle, and

101. Toxic Megacolon and Ogilvie's Soft Tissue
74. Community-Acquired
Pneumonia Syndrome 126. Head and Neck Infections
75. Nosocomial Pneumonia 102. Clinical Assessment of Renal 127. Infections in the
Function Immunocompromised Patient
76. Drowning
103. Biomarkers of Acute Kidney 128. Infectious Endocarditis
77. Acute Parenchymal Disease in
Injury 129. Fungal Infections
Pediatric Patients
104. Metabolic Acidosis and Alkalosis 130. Influenza
78. Acute Coronary Syndromes :
Therapy 105. Water Metabolism 131. Human Immunodeficiency Virus
79. Supraventricular Arrhythmias 106. Disorders of Calcium and Infection
Magnesium Metabolism 132. Tuberculosis
80. Ventricular Arrhythmias
107. Fluid and Volume Therapy in 133. Malaria and Other Tropical
81. Conduction Disturbances and
the ICU Infections in the Intensive Care
Cardiac Pacemakers
108. Fluids and Electrolytes in Unit
82. Myocarditis and Acute
Pediatrics 134. Acute Viral Syndromes
Myopathies
109. Acute Kidney Injury 135. Clostridium difficile Infection
83. Acquired and Congenital Heart
Disease in Children 110. Urinary Tract Obstruction 136. Anemia and RBC Transfusion
84. Pericardial Diseases 111. Contrast-Induced Acute Kidney 137. Blood Component Therapies
Injury
85. Emergency Heart Valve 138. Venous Thromboembolism in
Disorders 112. Glomerulonephritis Medical-Surgical Critically Ill
86. Infectious Endocarditis 113. Interstitial Nephritis Patients
87. Hypertensive Crisis : Emergency 114. Antimicrobial Stewardship 139. Monitoring of Coagulation
and Urgency 115. Prevention and Control of Status
88. Pathophysiology and Nosocomial Pneumonia 140. Anticoagulation in the Intensive

Classification of Shock States 116. Antimicrobial Agents with Care Unit
89. Resuscitation from Circulatory Primary Activity Against 141. Critical Care of the
Shock Gram-Negative Bacteria Hematopoietic Stem Cell
117. Antimicrobial Agents with Transplant Recipient
90. Inotropic Therapy
Primary Activity Against 142. Cardiovascular and
91. Mechanical Support in
Gram-Positive Bacteria Endocrinologic Changes
Cardiogenic Shock
118. Antimicrobial Agents Active Associated with Pregnancy
92. Portal Hypertension : Critical
Against Anaerobic Bacteria 143. Hypertensive Disorders in
Care Considerations
119. Selective Decontamination of Pregnancy
93. Hepatorenal Syndrome
the Digestive Tract 144. Acute Pulmonary Complications
94. Hepatopulmonary Syndrome During Pregnancy
120. Vascular Catheter-Related
95. Hepatic Encephalopathy Infections 145. Postpartum Hemorrhage
96. Fulminant Hepatic Failure 121. Septic Shock 146. Neurologic Critical Illness in
97. Calculous and Acalculous 122. Sepsis and Multiple Organ Pregnancy
147. Hyperglycemia and Blood 167. Pressure Ulcers Measurement
Glucose Control 168. Burns, Including Inhalation e5. Bedside Pulmonary Artery
148. Adrenal Insufficiency Injury Catheterization
149. Thyroid Disorders 169. Thoracic Trauma e6. Cardioversion and Defibrillation
150. Diabetes Insipidus 170. Abdominal Trauma e7. Transvenous and
151. Metabolic and Endocrine Crises 171. Pelvic and Major Long Bone Transcutaneous Cardiac Pacing
in the Pediatric Intensive Care Fractures e8. Ventricular Assist Device
Unit 172. Pediatric Trauma Implantation
152. General Principles of 173. Management of the Brain-Dead e9. Pericardiocentesis
Pharmacokinetics and Organ Donor e10. Paracentesis and Diagnostic
Pharmacodynamics Peritoneal Lavage
174. Donation After Cardiac Death
153. Poisoning : Overview of (Non-Heart-Beating Donation) e11. Thoracentesis
Approaches for Evaluation and
175. Conversations with Families of e12. Chest Tube Placement, Care,
Treatment
Critically Ill Patients and Removal
154. Resuscitation of Hypovolemic
176. Resource Allocation in the e13. Fiberoptic Bronchoscopy
Shock
Intensive Care Unit e14. Bronchoalveolar Lavage and
155. Mediastinitis *
177. Basic Ethical Principles in Protected Specimen Bronchial
156. Epistaxis Critical Care Brushing
157. Management of the 178. Determination of Brain Death e15. Percutaneous Dilatational
Postoperative Cardiac Surgical Tracheostomy
179. Building Teamwork to Improve
Patient
Outcomes e16. Esophageal Balloon Tamponade
158. Intensive Care Unit
180. The Pursuit of Performance e17. Nasoenteric Feeding Tube
Management of Lung Transplant
Excellence Insertion
Patients
181. Severity of Illness Indices and e18. Lumbar Puncture
159. Management of the
Outcome Prediction : Adults e19. Jugular Venous and Brain
Postoperative Liver Transplant
Patient 182. Severity of Illness Indices and Tissue Oxygen Tension
Outcome Prediction : Children Monitoring
160. Intestinal and Multivisceral
Transplantation : The Ultimate 183. Long-Term Outcomes of Critical e20. Intracranial Pressure
Treatment for Intestinal Failure Illness Monitoring
161. Aortic Dissection 184. Mass Critical Care e21. Indirect Calorimetry
162. Splanchnic Ischemia 185. Telemedicine in Intensive Care e22. Extracorporeal Membrane
186. Teaching Critical Care Oxygenation Cannulation
163. Abdominal Compartment
Syndrome e1. Difficult Airway Management e23. Bedside Laparoscopy in the
for Intensivists Intensive Care Unit
164. Extremity Compartment
Syndromes e2. Bedside Ultrasonography e24. Pediatric Intensive Care
Procedures
165. Thromboembolization and e3. Central Venous Catheterization
Thrombolytic Therapy IBC
e4. Arterial Cannulation and
166. Atheroembolization Invasive Blood Pressure
CONTRIBUTORS
Basem Abdelmalak, MD Roland Amathieu, MD, PhD

Professor of Anesthesiology Associate Professor
Director of Anesthesia for Bronchoscopic Surgery Critical Care Medicine and Anesthesiology
Departments of General Anesthesiology and Outcomes Research Henri Mondor Hospital - AP-HP
Anesthesiology Institute Associate Professor
Cleveland Clinic UPEC - School of Medicine
Cleveland, Ohio Créteil, France
Yasir Abu-Omar, MB ChB, DPhil, FRCS John Leo Anderson-Dam, MD

Consultant Cardiothoracic and Transplant Surgeon Assistant Clinical Professor
Papworth Hospital Department of Anesthesiology and Perioperative Medicine
Cambridge, Great Britain University of California Los Angeles
Los Angeles, California
Felice Achilli, MD
Chief of Cardiology Rajesh K. Aneja, MD
Cardiothoracic Department Associate Professor
San Gerardo University Hospital Department of Pediatrics and Critical Care Medicine
Monza, Italy University of Pittsburgh School of Medicine
Medical Director
Hernán Aguirre-Bermeo, MD Pediatric Intensive Care Unit
Intensive Care Department Children’s Hospital of Pittsburgh of UPMC
Hospital Sant Pau Pittsburgh, Pennsylvania
Barcelona, Spain
Massimo Antonelli, MD
Ayub Akbari, MD, MSc Professor of Intensive Care and Anesthesiology
Associate Professor Department of Anesthesiology and Intensive Care
Department of Medicine Agostino Gemelli University Hospital
University of Ottawa Rome, Italy
Senior Clinical Investigator
Clinical Epidemiology Program Zarah D. Antongiorgi, MD
Ottawa Hospital Research Institute Assistant Clinical Professor
Ottawa, Ontario, Canada Department of Anesthesiology and Perioperative Medicine
Division of Critical Care
Louis H. Alarcon, MD, FACS, FCCM David Geffen School of Medicine at UCLA
Associate Professor of Surgery and Critical Care Medicine Los Angeles, California
Pittsburgh, Pennsylvania Anastasia Antoniadou, MD, PhD
Associate Professor of Internal Medicine and Infectious Diseases
F. Luke Aldo, DO University General Hospital ATTIKON
Department of Anesthesiology National and Kapodistrian University of Athens Medical School
Hartford Hospital Athens, Greece
Hartford, Connecticut
Anupam Anupam, MBBS
Ali Al-Khafaji, MD, MPH, FACP, FCCP Attending Physician
Associate Professor Department of Medicine
Department of Critical Care Medicine Advocate Illinois Masonic Medical Center
Director Chicago, Illinois
Transplant Intensive Care Unit
Pittsburgh, Pennsylvania
ix
x Contributors
Lorenzo Appendini, ASLCN Arna Banerjee MD, FCCM

Presidio Ospedaliero di Saluzzo Associate Professor of Anesthesiology/Critical Care
Saluzzo (Cuneo), Italy Associate Professor of Surgery
Medical Education and Administration
Andrew C. Argent, MBBCh, MMed(Paediatrics), MD Assistant Dean for Simulation in Medical Education
(Paediatrics), DCH(SA), FCPaeds(SA) Vanderbilt University Medical Center
Professor Nashville, Tennessee
School of Child and Adolescent Health
University of Cape Town Shweta Bansal, MBBS, MD, FASN
Medical Director Professor of Medicine
Paediatric Intensive Care Division of Nephrology
Red Cross War Memorial Children’s Hospital University of Texas Health Sciences Center at San Antonio
Cape Town, South Africa San Antonio, Texas
John H. Arnold, MD Kaysie Banton, MD

Professor of Anaesthesia (Pediatrics) Assistant Professor of Surgery
Harvard Medical School University of Minnesota
Senior Associate Minneapolis, Minnesota
Department of Anesthesia and Critical Care
Medical Director Philip S. Barie, MD, MBA, FIDSA, FACS, FCCM
Respiratory Care/ECMO Professor of Surgery and Public Health
Children’s Hospital Weill Cornell Medicine of Cornell University
Boston, Massachusetts New York, New York
Stephen Ashwal, MD Igor Barjaktarevic, MD, MSc

Distinguished Professor of Pediatrics and Neurology Assistant Professor of Medicine
Chief Division of Pulmonary and Critical Care
Division of Pediatric Neurology David Geffen School of Medicine at UCLA
Department of Pediatrics Los Angeles, California
Loma Linda University School of Medicine
Loma Linda, California Barbara L. Bass, MD
John F., Jr., and Carolyn Bookout Presidential Distinguished Chair
Mark E. Astiz, MD Department of Surgery
Professor of Medicine Professor of Surgery
Hofstra Northwell School of Medicine Houston Methodist Hospital
Chairman Houston, Texas
Department of Medicine Professor of Surgery
Lenox Hill Hospital Weill Cornell Medicine of Cornell University
New York, New York New York, New York
Arnold S. Baas, MD, FACC, FACP Gianluigi Li Bassi, MD, PhD

Associate Clinical Professor of Medicine Department of Pulmonary and Critical Care Medicine
University of California Los Angeles Hospital Clinic Calle Villarroel
David Geffen School of Medicine at UCLA Barcelona, Spain
Sarice L. Bassin, MD
Marie R. Baldisseri, MD, MPH, FCCM Medical Director, Stroke Program
Professor of Critical Care Medicine PeaceHealth Southwest Medical Center
University of Pittsburgh Medical Center Vancouver, Washington
Julie A. Bastarache, MD
Zsolt J. Balogh, MD, PhD, FRACS, FACS Assistant Professor of Medicine
Professor of Traumatology Division of Allergy, Pulmonary, and Critical Care Medicine
Department of Traumatology Vanderbilt University School of Medicine
John Hunter Hospital and University of Newcastle Nashville, Tennessee
Newcastle, New South Wales, Australia

Contributors xi
Daniel G. Bausch, MD, MPH&TM Adriana Bermeo-Ovalle, MD

Professor Assistant Professor
Department of Tropical Medicine Department of Neurological Sciences
Tulane School of Public Health and Tropical Medicine Rush University Medical Center
Clinical Associate Professor Chicago, Illinois
Department of Medicine
Section of Adult Infectious Diseases Gordon R. Bernard, BS, MD
Tulane Medical Center Professor of Medicine
New Orleans, Louisiana Department of Medicine
Vanderbilt University School of Medicine
Hülya Bayır, MD Nashville, Tennessee
Professor of Critical Care Medicine
University of Pittsburgh School of Medicine Cherisse D. Berry, MD
Director of Research, Pediatric Critical Care Medicine Clinical Instructor
Associate Director, Center for Free Radical and Antioxidant Health Department of Surgery
University of Pittsburgh Medical Center University of Maryland School of Medicine
Pittsburgh, Pennsylvania Baltimore, Maryland
Yanick Beaulieu, MD, FCRPC Beth Y. Besecker, MD

Cardiologue-Échocardiographiste/Intensiviste Assistant Professor of Medicine
Hôpital du Sacré-Coeur de Montréal Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine
Professeur Adjoint de Clinique The Ohio State University Wexner Medical Center
Université de Montréal Columbus, Ohio
Montréal, Québec, Canada
Joost Bierens, MD
Thomas M. Beaver, MD, MPH Professor of Emergency Medicine
Professor of Surgery VU University Medical Centre
Chief Amsterdam, The Netherlands
Division of Thoracic and Cardiovascular Surgery
University of Florida College of Medicine Walter L. Biffl, MD
Gainesville, Florida Associate Director of Surgery
Denver Health Medical Center
Gregory Beilman, MD Denver, Colorado
Deputy Chair Professor of Surgery
Department of Surgery University of Colorado
Director of System Critical Care Program Aurora, Colorado
University of Minnesota Health System
Minneapolis, Minnesota Thomas P. Bleck, MD, MCCM
Professor
Michael J. Bell, MD Departments of Neurological Sciences, Neurosurgery, Internal
Associate Professor Medicine, and Anesthesiology
Departments of Critical Care Medicine, Neurological Surgery, Rush Medical College
and Pediatrics Director
University of Pittsburgh School of Medicine Clinical Neurophysiology
Associate Director Rush University Medical Center
Safar Center for Resuscitation Research Chicago, Illinois
Thomas A. Bledsoe, MD
Giuseppe Bello, MD Clinical Associate Professor of Medicine
Department of Anesthesia and Intensive Care Division of Critical Care
Agostino Gemelli University Hospital Pulmonary and Sleep Medicine
Università Cattolica del Sacro Cuore The Warren Alpert Medical School at Brown University
Rome, Italy Vice-Chair
Ethics Committee
Peyman Benharash, MD Rhode Island Hospital
Assistant Professor of Bioengineering Providence, Rhode Island
Division of Cardiothoracic Surgery
University of California Los Angeles
David Geffen School of Medicine at UCLA

xii Contributors
Karen C. Bloch, MD, MPH, FIDSA, FACP Sara T. Burgardt, MD, PharmD
Associate Professor Subspecialty Fellow
Departments of Medicine (Infectious Diseases) and Health Policy Adult Nephrology
Vanderbilt University Medical Center Department of Medicine
Nashville, Tennessee Division of Nephrology
University of North Carolina
Desmond Bohn, MD Chapel Hill, North Carolina
Professor of Pediatrics and Anesthesia
University of Toronto Sherilyn Gordon Burroughs, MD
Toronto, Ontario Associate Professor of Surgery
Weill Cornell Medicine of Cornell University
David Boldt, MD, MS Houston Methodist Hospital
Assistant Clinical Professor, Critical Care Medicine Sherrie and Alan Conover Center for Liver Disease and
Chief, Trauma Anesthesiology Transplantation
University of California Los Angeles Houston, Texas
Los Angeles, California Clifton W. Callaway, MD, PhD
Professor of Emergency Medicine
Geoffrey J. Bond, MD Executive Vice-Chairman of Emergency Medicine
Assistant Professor in Transplant Surgery Ronald D. Stewart Endowed Chair of Emergency Medicine Research
Thomas E. Starzl Transplantation Institute University of Pittsburgh School of Medicine
University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania
Transplant Director
Pediatric Intestinal Care Center Peter M.A. Calverley, MB ChB, MD
Children’s Hospital of Pittsburgh of UPMC Professor of Respiratory Medicine
Pittsburgh, Pennsylvania Respiratory Researach Department
University of Liverpool
Michael J. Bradshaw, MD Liverpool, Great Britain
Resident Physician
Department of Neurology John Camm, QHP, MD, BsC, FMedSci, FRCP, FRCP(E),
Vanderbilt University School of Medicine FRCP(G), FACC, FESC, FAHA, FHRS, CStJ
Nashville, Tennessee Professor of Clinical Cardiology
Clinical Academic Group
Luca Brazzi, MD Cardiovascular and Cell Sciences Research Institute
Associate Professor St. George’s University of London
Department of Anesthesia and Intensive Care Medicine London, Great Britain
S. Giovanni Battista Molinette Hospital
University of Turin Andre Campbell, MD
Turin, Italy Professor of Surgery
School of Medicine
Serge Brimioulle, MD, PhD University of California San Francisco
Professor of Intensive Care San Francisco, California
Department of Intensive Care
Erasme Hospital Diane M. Cappelletty, RPh, PharmD
Université Libre de Bruxelles Associate Professor of Clinical Pharmacy
Brussels, Belgium Chair
Department of Pharmacy Practice
Itzhak Brook, MD Co-Director
Professor of Pediatrics The Infectious Disease Research Laboratory
Georgetown University School of Medicine University of Toledo College of Pharmacy and Pharmaceutical
Washington, DC Sciences
Toledo, Ohio
Richard C. Brundage, PharmD, PhD, FISoP
Distinguished University Teaching Professor Joseph A. Carcillo, MD
Professor of Experimental and Clinical Pharmacology Associate Professor
University of Minnesota College of Pharmacy Departments of Critical Care Medicine and Pediatrics
Minneapolis, Minnesota University of Pittsburgh School of Medicine

Contributors xiii
Edward D. Chan, MD Staci Collins, RD, CNSC

Staff Physician Senior Dietitian
Pulmonary Section Department of Food and Nutrition Services
Denver Veterans Affairs Medical Center UC Davis Children’s Hospital
National Jewish Health Sacramento, California
Denver, Colorado
Gulnur Com, MD
Satish Chandrashekaran, MD Associate Professor of Clinical Pediatrics
Assistant Professor of Medicine University of Southern California Keck School of Medicine
Division of Pulmonary, Critical Care, and Sleep Medicine Los Angeles, California
Lung Transplantation Program
University of Florida College of Medicine Chris C. Cook, MD
Gainesville, Florida Assistant Professor of Cardiothoracic Surgery
Lakhmir S. Chawla, MD Pittsburgh, Pennsylvania
Associate Professor of Medicine
George Washington University Medical Center Robert N. Cooney, MD, FACS, FCCM
Washington, DC Professor and Chairman
Department of Surgery
David C. Chen, MD SUNY Upstate Medical University
Associate Professor of Clinical Surgery Syracuse, New York
Associate Director of Surgical Education Susan J. Corbridge, PhD, APN
David Geffen School of Medicine at UCLA Clinical Associate Professor
Los Angeles, California College of Nursing and Department of Medicine
Director of Graduate Clinical Studies
Amit Chopra, MD College of Nursing
Assistant Professor of Medicine University of Illinois at Chicago
Division of Pulmonary and Critical Care Medicine Chicago, Illinois
Albany Medical College
Albany, New York Thomas C. Corbridge, MD
Professor of Medicine
Robert S.B. Clark, MD Division of Pulmonary and Critical Care Medicine
Professor of Critical Care Medicine Department of Medicine
Chief Northwestern University Feinberg School of Medicine
Pediatric Critical Care Medicine Chicago, Illinois
Associate Director Oliver A. Cornely, MD
Safar Center for Resuscitation Research Professor of Internal Medicine
Pittsburgh, Pennsylvania Director of Translational Research
Cologne Excellence Cluster on Cellular Stress Responses in Aging-
Jonathan D. Cohen, MD, PhD Associated Diseases (CECAD)
Robert Bendheim and Lynn Bendheim Thoman Professor in Director
Neuroscience Clinical Trials Center Cologne (CTCC)
Professor of Psychology University of Cologne
Princeton University Cologne, Germany
Co-Director Princeton Neuroscience Institute
Princeton, New Jersey Marie L. Crandall, MD, MPH
Professor of Surgery
Stephen M. Cohn, MD, FACS University of Florida College of Medicine
Witten B. Russ Professor of Surgery Jacksonville, Florida
University of Texas Health Science Center
San Antonio, Texas Andrej Čretnik, MD, PhD
Professor of Traumatology
Kelli A. Cole, PharmD, BCPS University Clinical Center Maribor
Antibiotic Steward Pharmacist Maribor, Slovenia
Department of Pharmacy Services
University of Toledo Medical Center
Toledo, Ohio

xiv Contributors
David Crippen, MD, FCCM Jeffrey Dellavolpe, MD, MPH

Professor of Critical Care Medicine Critical Care Medicine
University of Pittsburgh University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania Pittsburgh, Pennsylvania
Chasen Ashley Croft, MD Anne Marie G.A. De Smet, MD, PhD

Assistant Professor of Surgery Anesthesiologist-Intensivist
Department of Surgery Afdelingshoofd Intensive Care Volwassenen
University of Florida Health Science Center Head of Department of Critical Care
Gainesville, Florida University Medical Center Groningen
Groningen, The Netherlands
Elliott D. Crouser, MD
Professor of Medicine Anahat Dhillon, MD
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine Associate Professor
The Ohio State University Wexner Medical Center Department of Anesthesiology and Perioperative Medicine
Columbus, Ohio University of California Los Angeles
Burke A. Cunha, MD, MACP
Chief Rajeev Dhupar, MD
Infectious Disease Division Resident
Winthrop-University Hospital Division of General Surgery
Mineola, New York University of Pittsburgh Medical Center
Professor of Medicine Pittsburgh, Pennsylvania
State University of New York School of Medicine
Stony Brook, New York Rochelle A. Dicker, MD
Professor
Cheston B. Cunha, MD Departments of Surgery and Anesthesia
Assistant Professor of Medicine University of California San Francisco
Division of Infectious Disease San Francisco, California
Medical Director
Antimicrobial Stewardship Program Francesca Di Muzio, MD
The Warren Alpert Medical School of Brown University Department of Anesthesiology and Intensive Care
Providence, Rhode Island Agostino Gemelli University Hospital
Università Cattolica del Sacro Cuore
J. Randall Curtis, MD, MPH Rome, Italy
Division of Pulmonary and Critical Care Medicine Michael N. Diringer, MD
University of Washington School of Medicine Professor of Neurology and Neurosurgery
Seattle, Washington Associate Professor of Anesthesiology and Occupational Therapy
Washington University School of Medicine in St. Louis
Heidi J. Dalton, MD St. Louis, Missouri
Professor of Child Health
University of Arizona College of Medicine Conrad F. Diven, MD, MS
Phoenix, Arizona Assistant Trauma Director
Trauma Research Director
Joseph M. Darby, MD Abrazo West Campus Trauma Center
Professor of Critical Care Medicine and Surgery Goodyear, Arizona
Medical Director Peter Doelken, MD
Trauma ICU Associate Professor of Medicine
UPMC-Presbyterian Hospital Division of Pulmonary and Critical Care Medicine
Pittsburgh, Pennsylvania Albany Medical College
Albany, New York
John D. Davies, MA, RRT, FAARC, FCCP
Clinical Research Coordinator Michael Donahoe, MD
Division of Pulmonary, Allergy, and Critical Care Medicine Professor of Medicine
Duke University Medical Center Division of Pulmonary, Allergy, and Critical Care Medicine
Durham, North Carolina University of Pittsburgh School of Medicine

Contributors xv
Caron L. Boyd Dover, MD Shane W. English, MD, MSc, FRCPC

Chief Associate Scientist
Cardiothoracic Imaging Clinical Epidemiology Program
Medical Director of CT Ottawa Hospital Research Institute
Assistant Professor of Radiology Assistant Professor of Medicine (Critical Care)
Department of Radiology University of Ottawa
Wake Forest School of Medicine Intensivist
Winston Salem, North Carolina Department of Critical Care
The Ottawa Hospital
Brian K. Eble, MD Ottawa, Ontario, Canada
Associate Professor of Pediatrics
University of Arkansas for Medical Sciences Brent Ershoff, MD
Little Rock, Arkansas Clinical Instructor
Department of Anesthesiology and Perioperative Medicine
Charles L. Edelstein, MD, PhD, FAHA David Geffen School of Medicine at UCLA
Professor of Medicine Los Angeles, California
Division of Renal Diseases and Hypertension
University of Colorado Denver Joel H. Ettinger, BS, MHA
Aurora, Colorado President
Category One Inc.
Randolph Edwards, MD Pittsburgh, Pennsylvania
Assistant Professor of Surgery
University of Connecticut School of Medicine Josh Ettinger, MBA
Surgical Critical Care Category One, Inc.
Department of Surgery Pittsburgh, Pennsylvania
Hartford Hospital
Hartford, Connecticut David C. Evans, MD
Assistant Professor of Surgery
Elwaleed A. Elhassan, MBBS, FACP, FASN Department of Surgery
Assistant Professor of Medicine (Nephrology) The Ohio State University
Wayne State University School of Medicine Columbus, Ohio
Detroit, Michigan
Gregory T. Everson, MD
E. Wesley Ely, MD, MPH Professor of Medicine
Professor of Medicine Division of Gastroenterology and Hepatology
Department of Allergy, Pulmonary, and Criticial Care Medicine University of Colorado Denver
Vanderbilt University Medical Center Director of Hepatology
Nashville, Tennessee Hepatology and Transplant Center
University of Colorado Hospital
Lillian L. Emlet, MD, MS, FACEP, FCCM Aurora, Colorado
Assistant Professor
Departments of Critical Care Medicine and Emergency Medicine Chiara Faggiano, MD
Associate Program Director Department of Anesthesia and Critical Care Medicine
IM-CCM Fellowship of the MCCTP S. Giovanni Battista Mollinette Hospital
University of Pittsburgh Medical Center University of Turin
Pittsburgh, Pennsylvania Turin, Italy
Amir Emtiazjoo, MD, MSc Jeff Fair, MD

Assistant Professor of Medicine Professor
Division of Pulmonary, Critical Care, and Sleep Medicine Department of Surgery
Lung Transplantation Program University of Texas Medical Branch
University of Florida College of Medicine Galveston, Texas
Gainesville, Florida
Ronald J. Falk, MD
Allen Brewster Distinguished Professor of Medicine
Director
UNC Kidney Center
Chairman
Chapel Hill, North Carolina

xvi Contributors
Brenna Farmer, MD Ericka L. Fink, MD, MS

Assistant Professor of Medicine Associate Professor of Critical Care Medicine
Department of Emergency Medicine University of Pittsburgh School of Medicine
Weill Cornell Medicine of Cornell University Children’s Hospital of Pittsburgh of UPMC
Assistant Residency Director Associate Director
Department of Emergency Medicine Safar Center for Resuscitation Research
New York Presbyterian Hospital Pittsburgh, Pennsylvania
New York, New York
Mitchell P. Fink, MD†
Rory Farnan, MB, BCh, BAO Professor of Surgery and Anesthesiology
Division of Cardiology Vice Chair for Critical Care
Cooper University Hospital Department of Surgery
Camden, New Jersey David Geffen School of Medicine at UCLA
Alan P. Farwell, MD
Associate Professor of Medicine Brett E. Fortune, MD
Chair Assistant Professor of Medicine (Digestive Diseases) and of Surgery
Division of Endocrinology, Diabetes, and Nutrition (Transplant)
Boston University School of Medicine Associate Program Director
Director Gastroenterology Fellowship
Endocrine Clinics Yale School of Medicine
Boston Medical Center New Haven, Connecticut
Boston, Massachusetts
Barry I. Freedman, MD
Carinda Feild, PharmD, FCCM Professor and Chief
Assistant Dean and Associate Professor Department of Internal Medicine
Department of Pharmacotherapy and Translational Research Section on Nephrology
University of Florida College of Pharmacy Wake Forest School of Medicine
Seminole, Florida Winston-Salem, North Carolina
David Feller-Kopman, MD, FACP Elchanan Fried, MD

Associate Professor of Medicine, Otolaryngology - Head and Neck Senior Physician
Surgery Department of Medicine
Department of Pulmonary and Critical Care Medicine Hadassah Medical Centers
The Johns Hopkins University Jerusalem, Israel
Director
Bronchoscopy and Interventional Pulmonology Kwame Frimpong, MD
Johns Hopkins University Medical Institutions Clinical Research Coordinator
Baltimore, Maryland Vanderbilt University Medical Center
Nashville, Tennessee
Kathryn Felmet, MD
Assistant Professor Rajeev K. Garg, MD, MS
Departments of of Critical Care Medicine and Pediatrics Assistant Professor of Neurological Sciences and Neurosurgery
University of Pittsburgh School of Medicine Rush University Medical Center
Pittsburgh, Pennsylvania Chicago, Illinois
Miguel Ferrer, MD, PhD Raúl J. Gazmuri, MD, PhD, FCCM

Department of Pneumology Professor of Medicine
Respiratory Institute Professor of Physiology and Biophysics
Hospital Clinic Director
IDIBAPS Resuscitation Institute
CibeRes Rosalind Franklin University of Medicine and Science
Associate Professor Director of Critical Care Medicine
Department of Medicine Captain James A. Lovell Federal Health Care Center
University of Barcelona North Chicago, Illinois
Barcelona, Spain
†Deceased.

Contributors xvii
Robert H. Geelkerken, Prof Dr Diana J. Goodman, MD

Medisch Spectrum Twente Assistant Professor
and Faculty of Science and Technology and Experimental Center of Department of Neurological Sciences
Technical Medicine Rush University Medical Center
University of Twente Chicago, Illinois
Enschede, The Netherlands
Shankar Gopinath, MD
Todd W.B. Gehr, MD Associate Professor of Neurosurgery
Sir Hans A. Krebs Chair of Nephrology Baylor College of Medicine
Department of Internal Medicine Houston, Texas
Division of Nephrology
Virginia Commonwealth University School of Medicine John Gorcsan, III, MD
Richmond, Virginia Professor of Medicine
Division of Cardiology
Michael A. Gentile, RRT, FAARC, FCCM University of Pittsburgh
Associate in Research Pittsburgh, Pennsylvania
Division of Pulmonary and Critical Care Medicine
Duke University Medical Center Yaacov Gozal, MD
Durham, North Carolina Associate Professor of Anesthesiology
Hebrew University
M. Patricia George, MD Chair
Assistant Professor of Medicine Department of Anesthesiology, Perioperative Medicine and Pain
University of Pittsburgh School of Medicine Treatment
UPMC Montefiore Hospital Shaare Zedek Medical Center
Pittsburgh, Pennsylvania Jerusalem, Israel
Herwig Gerlach, MD, PhD, MBA Jeremy D. Gradon, MD, FACP, FIDSA
Professor and Chairman Attending Physician
Department of Anesthesia, Intensive Care, and Pain Management Department of Medicine
Vivantes-Klinikum Neukölln Sinai Hospital of Baltimore
Berlin, Germany Associate Professor of Medicine
The Johns Hopkins University School of Medicine
Helen Giamarellou, MD, PhD Baltimore, Maryland
Professor of Internal Medicine and Infectious Diseases
Hygeia Hospital Cornelia R. Graves, MD
Athens, Greece Professor of Obstetrics and Gynecology
University of Tennessee College of Medicine
Fredric Ginsberg, MD Clinial Professor of Obstetrics and Gynecology
Associate Professor of Medicine Vanderbilt University School of Medicine
Division of Cardiovascular Disease Director of Perinatal Services
Cooper Medical School of Rowan University St. Thomas Health System
Camden, New Jersey Medical Director
Tennessee Maternal Fetal Medicine
Thomas G. Gleason, MD Nashville, Tennessee
Ronald V. Pellegrini Endowed Professor of Cardiothoracic Surgery
University of Pittsburgh School of Medicine Cesare Gregoretti, MD
Chief Department of Biopathology and Medical Biotechnologies
Division of Cardiac Surgery (DIBIMED)
Heart and Vascular Institute Section of Anesthesia, Analgesia, Intensive Care, and Emergency
Director Policlinico P. Giaccone University of Palermo
Center for Thoracic Aortic Disease Palermo, Italy
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania Andreas Greinacher, MD
Institute for Immunology and Transfusion Medicine
Corbin E. Goerlich, MD University Medicine Greifswald
The University of Texas Medical School at Houston Department of Anesthesiology and Intensive Care Medicine
Houston, Texas Greifswald, Germany

xviii Contributors
Michael A. Gropper, MD, PhD Jonathan R. Hiatt, MD

Professor and Chair Professor of Surgery
Department of Anesthesia and Perioperative Care Vice Dean for Faculty
University of California San Francisco David Geffen School of Medicine at UCLA
San Francisco, California Los Angeles, California
Paul O. Gubbins, PharmD Robert W. Hickey, MD FAAP, FAHA

Associate Dean Associate Professor of Pediatrics
Vice Chair and Professor University of Pittsburgh School of Medicine
Division of Pharmacy Practice and Administration Department of Emergency Medicine
UMKC School of Pharmacy at Missouri State University Children’s Hospital of Pittsburgh of UPMC
Springfield, Missouri Pittsburgh, Pennsylvania
Vadim Gudzenko, MD Thomas L. Higgins, MD, MBA

Assistant Clinical Professor Professor
Departments of Anesthesiology and Perioperative Medicine Departments of Medicine, Anesthesia, and Surgery
David Geffen School of Medicine at UCLA Chief Medical Officer
Los Angeles, California Baystate Franklin Medical Center and BH Northern Region
Baystate Noble Hospital and BH Western Region
Kyle J. Gunnerson, MD Westfield, Massachusetts
Associate Professor of Emergency Medicine
Chief, Division of Emergency Critical Care Nicholas S. Hill, MD, FPVRI
University of Michigan Medical School Professor of Medicine
Ann Arbor, Michigan Chief
Division of Pulmonary, Critical Care, and Sleep Medicine
Fahim A. Habib, MD, MPH, FACS Tufts University Medical Center
Assistant Professor of Surgery Boston, Massachusetts
DeWitt Daughtry Department of Surgery
University of Miami Miller School of Medicine Swapnil Hiremath, MD, MPH
Director Assistant Professor
Department of Critical Care Department of Medicine
University of Miami Hospital University of Ottawa
Attending Trauma Surgeon Senior Clinical Investigator
Ryder Trauma Center Clinical Epidemiology Program
Jackson Memorial Hospital Ottawa Hospital Research Institute
Miami, Florida Ottawa, Ontario, Canada
Brian G. Harbrecht, MD Gerald A. Hladik, MD

Professor of Surgery Doc J Thurston Distinguished Professor of Medicine
University of Louisville School of Medicine Interim Chief
Louisville, Kentucky Division of Nephrology and Hypertension
UNC Kidney Center
Yenal I.J. Harper, MD, ABIM University of North Carolina
Cardiovascular Disease Fellow Chapel Hill, North Carolina
University of Tennessee Health Science Center
Memphis, Tennessee Steven M. Hollenberg, MD
Moustafa Hassan, MD Cooper Medical School of Rowan University
Associate Professor Director
Departments of Surgery and Anesthesiology Coronary Care Unit
State University of New York Cooper University Hospital
SUNY Upstate Medical University Camden, New Jersey
Syracuse, New York
Eric Hoste, MD, PhD
Jan A. Hazelzet, MD, PhD Associate Professor
Professor in Healthcare Quality and Outcome Department of Intensive Care Medicine
Chief Medical Information Officer Ghent University Faculty of Medicine and Health Sciences
Vice Director Ghent University Hospital
Strategy and Policy IT Ghent, Belgium
Erasmus Medical Center Senior Clinical Investigator
Rotterdam, The Netherlands Research Fund-Flanders (FWO)
Brussels, Belgium

Contributors xix
Albert T. Hsu, MD Ashutosh P. Jadhav, MD, PhD

Assistant Professor of Surgery Assistant Professor
University of Florida College of Medicine Departments of Neurology and Neurological Surgery
Jacksonville, Florida University of Pittsburgh
David T. Huang, MD, MPH
Associate Professor David Jiménez, MD, PhD
Departments of Critical Care Medicine and Emergency Medicine Associate Professor of Medicine (Respiratory Medicine)
Director Alcalá de Henares University
Multidisciplinary Acute Care Research Organization Chief, Venous Thromboembolism Programme
University of Pittsburgh School of Medicine Hospital Ramón y Cajal
Pittsburgh, Pennsylvania Madrid, Spain
J. Terrill Huggins, MD Jimmy Johannes, MD

Associate Professor of Medicine Fellow, Department of Pulmonary and Critical Care Medicine
Pulmonary, Critical Care, Allergy, and Sleep Medicine David Geffen School of Medicine at UCLA
Medical University of South Carolina Los Angeles, California
Charleston, South Carolina
Janeen Rene Jordan, MD
Russell D. Hull, MBBS, MSc, FRCPC, FACP, FCCP Department of Surgery
Professor of Medicine University of Florida
University of Calgary Faculty of Medicine Gainesville, Florida
Calgary, Alberta, Canada
Philippe G. Jorens, MD, PhD
Joseph Abdellatif Ibrahim, MD Professor and Chair
Associate Program Director Department of Critical Care Medicine
Department of General Surgery Professor of Clinical Pharmacology and Toxicology
Orlando Health University of Antwerp and Antwerp University Hospital
Orlando, Florida Antwerp, Belgium
Angie Ingraham, MD Mathieu Jozwiak, MD

Assistant Professor of Surgery Medical Intensive Care Unit
University of Wisconsin Bicêtre University Hospital
Madison, Wisconsin Paris-South University
Le Kremlin-Bicêtre, France
Margaret L. Isaac, MD
Assistant Professor of Medicine Rose Jung, PharmD, MPH, BCPS
University of Washington School of Medicine Clinical Associate Professor
Seattle, Washington Department of Pharmacy Practice
University of Toledo College of Pharmacy and Pharmaceutical
James P. Isbister, BSc(Med), MB, BS, FRACP, FRCPA Sciences
Consultant in Haematology and Transfusion Medicine Toledo, Ohio
Clinical Professor of Medicine
Sydney Medical School Aanchal Kapoor, MD
Royal North Shore Hospital of Sydney Associate Program Director
Conjoint Professor of Medicine Department of Critical Care Medicine
University of New South Wales Cleveland Clinic
Sydney, Australia Cleveland, Ohio
Adjunct Professor of Medicine
Monash University David C. Kaufman, MD, FCCM
Melbourne, Australia Professor of Surgery, Anesthesia, Internal Medicine, Medical
Humanities and Bioethics, and Urology
Frederique A. Jacquerioz, MD, MPH, CTropMed University of Rochester
Clinical Assistant Professor Rochester, New York
Department of Tropical Medicine
Tulane School of Public Health and Tropical Medicine A. Murat Kaynar, MD, MPH
New Orleans, Louisiana Associate Professor
Department of Tropical and Humanitarian Medicine Departments of Critical Care Medicine and Anesthesiology
Geneva University Hospitals University of Pittsburgh School of Medicine
Geneva, Switzerland The Clinical Research, Investigation, and Systems Modeling of Acute
Illness (CRISMA) Center

xx Contributors
John A. Kellum, MD Robert L. Kormos, MD, FRCS(C), FAHA

Professor of Critical Care Medicine Professor
University of Pittsburgh Department of Surgery
Pittsburgh, Pennsylvania University of Pittsburgh School of Medicine
Director
Orlando Kirton, MD Artificial Heart Program
Ludwig J. Pyrtek, MD, Chair of Surgery Co-Director
Department of Surgery Heart Transplantation
Hartford Hospital Medical Director
Hartford, Connecticut Vital Engineering
Professor and Vice Chairman University of Pittsburgh Medical Center
University of Connecticut School of Medicine
Farmington, Connecticut Lucy Z. Kornblith, MD
Fellow
Jason Knight, MD Trauma and Critical Care
Emergency Department Medical Director University of California San Francisco
Maricopa Medical Center San Francisco, California
Phoenix, Arizona
Roman Košir, MD, PhD
Patrick M. Kochanek, MD, MCCM Chief
Ake N. Grenvik Professor in Critical Care Medicine Emergency Center
Professor and Vice Chairman Attending Physician
Department of Critical Care Medicine Trauma Department
Professor of Anesthesiology, Pediatrics, Bioengineering, and Clinical University Clinical Center Maribor
and Translational Science Maribor, Slovenia
Director Robert M. Kotloff, MD
Safar Center for Resuscitation Research Chairman
Pittsburgh, Pennsylvania Department of Pulmonary Medicine
Respiratory Institute
Philipp Koehler, MD Cleveland Clinic
Resident Physician Cleveland, Ohio
Department of Internal Medicine
University Hospital Cologne Rosemary A. Kozar, MD, PhD
Cologne Excellence Cluster on Cellular Stress Responses in Aging- Professor of Surgery
Associated Diseases (CECAD) University of Maryland
Faculty of Medicine Baltimore, Maryland
University of Cologne
Cologne, Germany Wolf Benjamin Kratzert, MD, PhD
Assistant Clinical Professor
Jeroen J. Kolkman, Prof Dr Department of Anesthesiology and Perioperative Medicine
Department of Gastroenterology University of California Los Angeles
Medische Spectrum Twente Los Angeles, California
Enschede, The Netherlands
Department of Gastroenterology Anand Kumar, MD
University Medical Center Groningen Associate Professor
Groningen, The Netherlands Sections of Critical Care Medicine and Infectious Diseases
University of Manitoba
Marin H. Kollef, MD Winnipeg, Manitoba, Canada
Division of Pulmonary and Critical Care Medicine Associate Professor
Washington University School of Medicine in St. Louis Sections of Critical Care Medicine and Infectious Diseases
St. Louis, Missouri Robert Wood Johnson Medical School, UMDNJ
Camden, New Jersey
Cecilia Korb, MD, MSc
Research Fellow
Department of Paediatric Intensive Care
Royal Brompton Hospital
London, United Kingdom

Contributors xxi
Vladimir Kvetan, MD Jerrold H. Levy, MD, FAHA, FCCM

Director Professor of Anesthesiology
Jay B. Langner Critical Care System Director Associate Professor of Surgery
Division of Critical Care Medicine Co-Director
Montefiore Medical Center Cardiothoracic ICU
Albert Einstein College of Medicine Anesthesiology, Critical Care, and Surgery
Bronx, New York Duke University Hospital
Durham, North Carolina
Shawn D. Larson, MD, FACS
Assistant Professor of Surgery Mitchell M. Levy, MD
Division of Pediatric Surgery Professor of Medicine
University of Florida College of Medicine The Warren Alpert Medical School of Brown University
Gainesville, Florida Chief
Division of Critical Care, Pulmonary and Sleep Medicine
Gilles Lebuffe, MD Rhode Island Hospital
Professor of of Anaesthesiology and Intensive Care Medicine Providence, Rhode Island
Lille University School of Medicine
Lille University Hospital Anthony J. Lewis, MD
Lille, France General Surgery Resident
Constance Lee, MD University of Pittsburgh
Fellow Pittsburgh, Pennsylvania
Surgical Critical Care
Department of Surgery Catherine E. Lewis, MD
University of Florida College of Medicine Assistant Professor of Surgery
Gainesville, Florida Trauma, Emergency General Surgery, and Surgical Critical Care
Hans J. Lee, MD Los Angeles, California
Assistant Professor of Medicine
Director of Pleural Disease Service Susan J. Lewis, PharmD, BCPS
Fellowship Director Assistant Professor
Kopen Wang Interventional Pulmonary Fellowship Department of Pharmacy Practice
Division of Pulmonary/Critical Care Medicine University of Findlay College of Pharmacy
The Johns Hopkins University Findlay, Ohio
Baltimore, Maryland
Scott Liebman, MD, MPH
Angela M. Leung, MD, MSc Associate Professor
Assistant Clinical Professor of Medicine Department of Medicine
Division of Endocrinology University of Rochester Medical Center
David Geffen School of Medicine at UCLA Rochester, New York
VA Greater Los Angeles Healthcare System
Los Angeles, California Stuart L. Linas, MD
Rocky Mountain Professor of Renal Research
Allan D. Levi, MD, PhD, FACS Department of Internal Medicine
Chair University of Colorado School of Medicine
Department of Neurological Surgery Aurora, Colorado
Professor of Neurological Surgery, Orthopedics, and Rehabilitation Chief of Nephrology
Medicine Denver Health Medical Center
University of Miami Miller School of Medicine Denver, Colorado
Chief of Neurosurgery
Jackson Memorial Hospital Jason P. Linefsky, MD, MS
Miami, Florida Assistant Professor of Medicine
Division of Cardiology
Phillip D. Levin, MA, MB, BCHIR Emory University School of Medicine
Director Decatur, Georgia
Senior Lecturer
Department of Anesthesia Kerry Michael Link, MD, MBA
Hebrew University Professor of Radiology
Director Cardiology, Regenerative Medicine, and Translational Sciences
General Intensive Care Unit Department of Radiology
Shaare Zedek Medical Center Wake Forest School of Medicine
Jerusalem, Israel Winston-Salem, North Carolina

xxii Contributors
Pamela Lipsett, MD, MHPE Bernhard Maisch, MD, FESC, FACC

Warfield M. Firor Endowed Professorship Professor and Director
Department of Surgery Department of Cardiology
The Johns Hopkins University School of Medicine Marburg Heart Center
Baltimore, Maryland Marburg, Germany
Angela K.M. Lipshutz, MD, MPH Jordi Mancebo, MD

2015-2016 Severinghaus Assistant Professor Director
Department of Anesthesia and Perioperative Care Intensive Care Department
University of California San Francisco Hospital Sant Pau
San Francisco, California Barcelona, Spain
Alejandro J. Lopez-Magallon, MD Henry J. Mann, PharmD, FCCM, FCCP, FASHP

Assistant Professor of Medicine Dean and Professor
Division of Critical Care Medicine The Ohio State University College of Pharmacy
University of Pittsburgh School of Medicine Columbus, Ohio
Sanjay Manocha, MD, FRCPC
Andrew I.R. Maas, MD, PhD Medical Director
Professor and Chair Critical Care Unit
Department of Neurosurgery Division of Critical Care Medicine
University Hospital Antwerp and University of Antwerp Department of Medicine
Antwerp, Belgium Humber River Hospital
Toronto, Ontario, Canada
Neil R. MacIntyre, MD Assistant Professor
Professor of Medicine Department of Medicine
Duke University School of Medicine Queen’s University
Clinical Chief Kingston, Ontario, Canada
Pulmonary and Critical Care Division
Medical Director Daniel R. Margulies, MD, FACS
Respiratory Care Services Professor of Surgery
Duke University Medical Center Director
Durham, North Carolina Trauma Services and Acute Care Surgery
Associate Director, General Surgery
Duncan Macrae, MB, ChB, FRCA Cedars-Sinai Medical Center
Consultant Los Angeles, California
Department of Paediatric Intensive Care
Royal Brompton Hospital Paul E. Marik, MD, FCCP, FCCM
Senior Lecturer and Adjunct Reader Chief
Imperial College School of Medicine Division of Pulmonary and Critical Care Medicine
London, United Kingdom Department of Internal Medicine
Eastern Virginia Medical School
Michael C. Madigan, MD Norfolk, Virginia
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania Donald W. Marion, MD, MSc
Senior Clinical Consultant
Stefano Maggiolini, MD Division of Clinical Affairs
Chief of Cardiology The Defense and Veterans Brain Injury Center
Cardiovascular Department Silver Spring, Maryland
ASST-Lecco
San Leopoldo Mandic Hospital Merate Stephanie Markle, DO, MPH
Lecco, Italy Acute Care Surgery Fellow
Clinical Instructor
Aman Mahajan, MD, PhD University of Florida College of Medicine
Professor of Anesthesiology and Bioengineering Gainesville, Florida
Chair
Department of Anesthesiology Alvaro Martinez-Camacho, MD
David Geffen School of Medicine at UCLA Assistant Professor of Gastroenterology and Hepatology
Los Angeles, California University of Colorado Denver
Division of Digestive and Liver Health
Denver Health Hospital and Authority
Denver, Colorado

Contributors xxiii
Florian B. Mayr, MD, MPH Daniel R. Meldrum, MD

Assistant Professor of Critical Care Medicine Professor of Surgery
University of Pittsburgh School of Medicine Michigan State University College of Human Medicine
Pittsburgh, Pennsylvania Grand Rapids, Michigan
George V. Mazariegos, MD Joseph S. Meltzer, MD

Professor of Surgery and Critical Care Associate Clinical Professor
University of Pittsburgh School of Medicine Department of Anesthesiology and Perioperative Medicine
Director, Pediatric Transplantation University of California Los Angeles
Hillman Center for Pediatric Transplantation David Geffen School of Medicine at UCLA
Children’s Hospital of Pittsburgh of UPMC Los Angeles, California
Dieter Mesotten, MD, PhD
Joanne Mazzarelli, MD, FACC Associate Professor of Medicine
Division of Cardiovascular Disease Division of Intensive Care Medicine
Women’s Heart Program Katholieke Universiteit Leuven
Cooper University Hospital Leuven, Belgium
Cooper Medical School of Rowan University Kimberly S. Meyer, MSN, ACNP-BC
Camden, New Jersey Neurosurgery Nurse Practitioner
Trauma Institute
Steven A. McGloughlin, FCICM, FRACP, MPH&TM, University of Louisville Hospital
PGDipEcho Instructor in Nursing
Department of Intensive Care and Hyperbaric Medicine University of Louisville
The Alfred Hospital Louisville, Kentucky
Melbourne, Australia
Scott T. Micek, PharmD
Lauralyn McIntyre, MD, MSc Associate Professor of Pharmacy Practice
Senior Scientist St. Louis College of Pharmacy
Clinical Epidemiology Program St. Louis, Missouri
Ottawa Hospital Research Institute
Associate Professor of Medicine (Critical Care) David J. Michelson, MD
University of Ottawa Assistant Professor
Intensivist Departments of Pediatrics and Neurology
Department of Critical Care Loma Linda University Health
The Ottawa Hospital Loma Linda, California
Ottawa, Ontario, Canada
Dianne Mills, RD, CNSC
Anna W. McLean, MD Senior Dietitian
Department of Internal Medicine Department of Food and Nutrition Services
George Washington University School of Medicine UC Davis Children’s Hospital
VA Medical Center UC Davis Medical Center
Washington, DC Sacramento, California
John F. McNamara, BDSc, MDS (Adel), FICD, FADI, FPFA, Bartley Mitchell, MD
MRACDS (ENDO) Endovascular Neurosurgeon
Registrar—Associate Lecturer Baptist Medical Center
Center for Clinical Research Jacksonville, Florida
University of Queensland
Brisbane, Australia Aaron M. Mittel, MD
Clinical Fellow in Anaesthesia
Michelle K. McNutt, MD Department of Anesthesia, Critical Care, and Pain Medicine
Assistant Professor of Surgery Harvard Medical School
University of Texas Health Science Center at Houston Beth Israel Deaconess Medical Center
Houston, Texas Boston, Massachusetts
Lucido L. Ponce Mejia, MD Xavier Monnet, MD, PhD

Resident Physician Medical Intensive Care Unit
Department of Neurosurgery Paris-South University
Baylor College of Medicine Bicêtre Hospital
Houston, Texas Le Kremlin-Bicêtre, France

xxiv Contributors
John Montford, MD Bruno Mourvillier, MD

Assistant Professor of Medicine Assistant
University of Colorado School of Medicine Medical and Infectious Diseases Intensive Care
Aurora, Colorado Bichat-Claude Bernard Hospital
Paris 7 University
Frederick A. Moore, MD, MCCM Paris, France
Head Ricardo Muñoz, MD, FAAP, FCCM, FACC
Acute Care Surgery Professor
Department of Surgery Departments of Critical Care Medicine, Pediatrics, and Surgery
University of Florida College of Medicine University of Pittsburgh School of Medicine
Gainesville, Florida Chief
Pediatric Cardiac Critical Care
Laura J. Moore, MD Medical Director
Associate Professor of Surgery Global Business and Telemedicine
Chief of Surgical Critical Care Children’s Hospital of Pittsburgh of UPMC
The University of Texas Health Science Center Houston
Medical Director Kurt G. Naber, MD, PhD
Shock Trauma Intensive Care Unit Associate Professor of Urology
Texas Trauma Institute Technical University of Munich
Memorial Hermann Hospital Munich, Germany
Texas Medical Center
Houston, Texas Girish B. Nair, MD, FACP, FCCP
Director
Lisa K. Moores, MD Interstitial Lung Disease Program and Pulmonary Rehabilitation
Associate Dean for Student Affairs Internal Medicine
Office of the Dean Winthrop University Hospital
Professor of Medicine Mineola, New York
F. Edward Hebert School of Medicine Assistant Professor of Clinical Medicine
The Uniformed Services University of the Health Sciences Internal Medicine
Bethesda, Maryland SUNY Stony Brook
Stony Brook, New York
Colleen M. Moran, MD
Assistant Professor Jovany Cruz Navarro, MD
Departments of Anesthesiology and Critical Care Resident Physician
University of Pittsburgh School of Medicine Department of Anesthesiology
Pittsburgh, Pennsylvania Baylor College of Medicine
Houston, Texas
Alison Morris, MD, MS
Associate Professor of Medicine and Immunology Melissa L. New, MD
Division of Pulmonary, Allergy, and Critical Care Medicine Pulmonary and Critical Care Fellow
Vice Chair of Clinical Research Department of Medicine
Department of Medicine University of Colorado Denver
University of Pittsburgh School of Medicine Anschutz Medical Campus
Pittsburgh, Pennsylvania Aurora, Colorado
Thomas C. Mort, MD Jennifer Nguyen-Lee, MD

Assistant Professor of Surgery Assistant Clinical Instructor
University of Connecticut School of Medicine Department of Anesthesiology and Perioperative Medicine
Farmington, Connecticut Liver Transplant Anesthesia
Associate Director David Geffen School of Medicine at UCLA
Surgical Intensive Care Unit Los Angeles, California
Hartford Hospital
Hartford, Connecticut Michael S. Niederman, MD, MACP, FCCP, FCCM, FERS
Clinical Director
Michele Moss, MD Division of Pulmonary and Critical Care
Professor and Vice Chair New York Hospital
Department of Pediatrics Weill Cornell Medicine of Cornell University
University of Arkansas for Medical Sciences New York, New York
Little Rock, Arkansas

Contributors xxv
Alexander S. Niven, MD Joseph E. Parrillo, MD

Professor of Medicine Chairman
Uniformed Services University of the Health Sciences Heart and Vascular Hospital
Bethesda, Maryland Hackensack University Medical Center
Director of Medical Education and DIO Hackensack, New Jersey
Educational Resources Division Professor of Medicine
Madigan Army Medical Center Rutgers New Jersey Medical School
Tacoma, Washington Newark, New Jersey
Juan B. Ochoa, MD Rohit Pravin Patel, MD

Department of Surgery and Critical Care Medicine Assistant Professor
University of Pittsburgh School of Medicine Departments of Emergency Medicine, Anesthesiology, and Surgery
Pittsburgh, Pennsylvania Co-Director
Emergency Medicine Critical Care Fellowship
Mauro Oddo, MD Director of Critical Care Ultrasound
Staff Physician Surgical ICU
Head University of Florida Health Shands Hospital
Clinical Research Unit Gainesville, Florida
Department of Intensive Care Medicine
Centre Hospitalier Universitaire Vaudois (CHUV) – University David L. Paterson, MBBS (Hons), PhD, FRACP, FRCPA,
Hospital GDCE
Faculty of Biology Medicine Professor of Medicine
University of Lausanne Centre for Clinical Research (UQCCR)
Lausanne, Switzerland The University of Queensland
Consultant Infectious Diseases Physician
Patrick J. O’Neill, MD, PhD Department of Infectious Diseases
Clinical Associate Professor of Surgery Royal Brisbane and Women’s Hospital
University of Arizona College of Medicine Brisbane, Australia
Phoenix, Arizona
Trauma Medical Director Andrew B. Peitzman, MD
Abrazo West Campus Trauma Center Distinguished Professor of Surgery
Goodyear, Arizona Mark M. Ravitch Professor and Vice-Chair
University of Pittsburgh Vice President for Trauma and Surgical
Steven M. Opal, MD Services
Professor of Medicine Pittsburgh, Pennsylvania
Infectious Disease Division
The Warren Alpert Medical School of Brown University Daleen Aragon Penoyer, PhD, RN, CCRP, FCCM
Providence, Rhode Island Director
Center for Nursing Research and Advanced Nursing Practice
James P. Orlowski, MD Orlando Health
Division of Pediatric Critical Care Orlando, Florida
Community Hospital
Tampa, Florida Judith L. Pepe, MD
Senior Associate Director, Surgical Critical Care
Catherine M. Otto, MD Department of Surgery
J. Ward Kennedy-Hamilton Endowed Chair in Cardiology Hartford Hospital
Professor of Medicine Hartford, Connecticut
University of Washington School of Medicine Associate Professor of Surgery
Seattle, Washington University of Connecticut Medical Center
Farmington, Connecticut
Aravinda Page, MA, MB BChir, MRCS
Specialist Registrar Steve G. Peters, MD
Cardiothoracic Surgery Professor of Medicine
Papworth Hospital NHS Foundation Trust Division of Pulmonary and Critical Care Medicine
Cambridge, Great Britain Mayo Clinic
Rochester, Minnesota
Adrian Pilatz, MD, PhD

Clinic for Urology, Pediatric Urology, and Andrology
Justus-Liebig-University
Geissen, Germany

xxvi Contributors
Giovanni Piovesana, MD Davinder Ramsingh, MD

Fellow in Cardiothoracic Surgery Director of Clinical Research and Perioperative Ultrasound
Department of Surgery Associate Professor
University of Florida College of Medicine Department of Anesthesiology
Gainesville, Florida Loma Linda Medical Center
Loma Linda, California
Fred Plum, MD†
Department of Neurology Sarangarajan Ranganathan, MD
Weill Cornell Medicine of Cornell University Professor of Pathology
New York, New York University of Pittsburgh School of Medicine
Director of Anatomic Pathology
Kees H. Polderman, MD, PhD Division of Pediatric Pathology
Professor of Critical Care Medicine Children’s Hospital of Pittsburgh of UPMC
University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania
V. Marco Ranieri, MD
Murray M. Pollack, MD, MBA Policlinico Umberto I
Professor of Pediatrics Anesthesia and Critical Care Medicine
George Washington University School of Medicine and Health Sapienza Università di Roma
Sciences Rome, Italy
Director
Clinical Outcomes Research Sepehr Rejai, MD
Department of Critical Care Resident
Children’s National Medical Center Department of Anesthesiology and Perioperative Medicine
Washington, DC David Geffen School of Medicine at UCLA
Sebastian Pollandt, MD
Assistant Professor Jorge Reyes, MD
Department of Neurological Sciences Professor of Surgery
Rush University Medical Center Chief
Chicago, Illinois Division of Transplant Surgery
University of Washington School of Medicine
Peter J. Pronovost, MD Seattle, Washington
Professor
Departments of Anesthesiology/Critical Care Medicine and Surgery Joshua C. Reynolds, MD, MS
The Johns Hopkins University School of Medicine Assistant Professor
Baltimore, Maryland Department of Emergency Medicine
Michigan State University College of Human Medicine
Juan Carlos Puyana, MD, FACS, FACCP Grand Rapids, Michigan
Professor of Surgery, Critical Care Medicine, and Translational
Science Arsen D. Ristic, MD, PhD, FESC
Director Associate Professor of Internal Medicine (Cardiology)
Global Health Surgery Belgrade University School of Medicine
University of Pittsburgh School of Medicine Deputy Director
Pittsburgh, Pennsylvania Polyclinic of the Clinical Center of Serbia
Chief
Jin H. Ra, MD, FACS Interventional Pericardiology and Diseases of Pulmonary Circulation
Assistant Professor of Surgery Department of Cardiology
Medical Director, SICU Clinical Center of Serbia
Program Director, SCC Fellowship Belgrade, Serbia
University of Florida College of Medicine
Jacksonville, Florida Claudia S. Robertson, MD
Professor
Thomas G. Rainey, MD Department of Neurosurgery
President Baylor College of Medicine
Critical Medicine Houston, Texas
Bethesda, Maryland
Emmanuel Robin, MD, PhD
Head, Anesthesia—Cardiothoracic Intensive Care
Lille University Hospital
†Deceased. Lille, France

Contributors xxvii
Todd W. Robinson, MD Santhosh Sadasivan, MD

Assistant Professor Senior Research Assistant
Department of Internal Medicine Department of Neurosurgery
Section on Nephrology Baylor College of Medicine
Wake Forest School of Medicine Houston, Texas
Winston-Salem, North Carolina
Howard L. Saft, MD, MSHS
Ferran Roche-Campo, MD Assistant Professor
Intensive Care Department Department of Medicine
Hospital Verge de la Cinta David Geffen School of Medicine at UCLA
Tortosa, Tarragona, Spain VA Greater Los Angeles Healthcare System
Bryan Romito, MD National Jewish Health
Assistant Professor of Anesthesiology and Pain Management Denver, Colorado
University of Texas Southwestern Medical Center
Dallas, Texas Rajan Saggar, MD
Matthew R. Rosengart, MD, MPH David Geffen School of Medicine at UCLA
Associate Professor Los Angeles, California
Departments of Surgery and Critical Care Medicine
University of Pittsburgh Manish K. Saha, MBBS
Pittsburgh, Pennsylvania Postdoctoral Fellow
Department of Internal Medicine
Gordon D. Rubenfeld, MD, MSc Division of Nephrology
Professor of Medicine University of Alabama Birmingham
Interdepartmental Division of Critical Care Medicine Birmingam, Alabama
University of Toronto
Chief Juan C. Salgado, MD
Program in Trauma, Emergency, and Critical Care Assistant Professor of Medicine
Sunnybrook Health Sciences Center Division of Pulmonary, Critical Care, Sleep, and Occupational
Toronto, Ontario, Canada Medicine
Lung Transplantation Program
Lewis J. Rubin, MD Indiana University School of Medicine
Emeritus Professor Indianapolis, Indiana
University of California San Diego Joan Sanchez-de-Toledo, MD, PhD
La Jolla, California Assistant Professor of Medicine
Division of Critical Care
Jeffrey A. Rudolph, MD University of Pittsburgh School of Medicine
Assistant Professor of Pediatrics Clinical Director
University of Pittsburgh School of Medicine Cardiac Intensive Care Unit
Director, Intestinal Care and Rehabilitation Center Children’s Hospital of Pittsburgh of UPMC
Children’s Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania
Vivek R. Sanghani, MD
Mario Rueda, MD Subspecialty Fellow
Assistant Professor of Surgery Adult Nephrology
The Johns Hopkins University School of Medicine Department of Medicine
Baltimore, Maryland Division of Nephrology
Randall A. Ruppel, MD Chapel Hill, North Carolina
Assistant Professor of Pediatrics
Virginia Tech Carilion School of Medicine Cristina Santonocito, MD
Medical Director Department of Anesthesia and Intensive Care
Neonatal/Pediatric Transport Team IRCSS-ISMETT-UPMC
Carilion Clinic Children’s Hospital Palermo, Italy
Roanoke, Virginia

xxviii Contributors
Penny Lynn Sappington, MD Donna L. Seger, MD

Assistant Professor of Critical Care Medicine Associate Professor of Medicine and Emergency Medicine
University of Pittsburgh School of Medicine Vanderbilt University Medical Center
Medical Director Medical Director and Executive Director
Surgical Intensive Care Unit Tennessee Poison Center
University of Pittsburgh Medical Center Nashville, Tennessee
Sixten Selleng, MD
John Sarko, MD Senior Physician
Clinical Attending Physician Department of Anaesthesiology and Intensive Care
Department of Emergency Medicine University Medicine Greifswald
Maricopa Medical Center Greifswald, Germany
University of Arizona—Phoenix School of Medicine
Phoenix, Arizona Frank W. Sellke, MD
Karlson and Karlson Professor of Surgery
Richard H. Savel, MD, FCCM Chief of Cardiothoracic Surgery
Associate Professor The Warren Alpert Medical School of Brown University
Departments of Clinical Medicine and Neurology Providence, Rhode Island
Albert Einstein College of Medicine
Medical Co-Director Kinjal N. Sethuraman, MD, MPH
Surgical Intensive Care Unit Assistant Professor
Montefiore Medical Center Department of Emergency Medicine
New York, New York University of Maryland School of Medicine
Baltimore, Maryland
Irina Savelieva, MD, PhD
Lecturer in Cardiology Robert L. Sheridan, MD
Division of Cardiac and Vascular Sciences Medical Director, Burn Service
St. Georges University of London Shriners Hospital for Children
London, United Kingdom Boston, Massachusetts
Anton C. Schoolwerth, MD Ariel L. Shiloh, MD

Professor of Medicine Assistant Professor of Clinical Medicine and Neurology
Dartmouth University Geisel School of Medicine Director
Lebanon, New Hampshire Critical Care Medicine Consult Service
Albert Einstein College of Medicine
Christopher K. Schott, MD, MS, RDMS Montefiore Medical Center
Assistant Professor New York, New York
Department of Critical Care Medicine
Department of Emergency Medicine Pierre Singer, MD
Director of Critical Care Ultrasonography Department of General Intensive Care
VA Pittsburgh Healthcare Systems and University of Pittsburgh/ Rabin Medical Center
UPMC Petah Tikva and the Sackler School of Medicine
Pittsburgh, Pennsylvania Tel Aviv, Israel
Robert W. Schrier, MD Sumit P. Singh, MBBS, MD

Professor Emeritus Assistant Professor of Anesthesiology and Intensive Care
Department of Medicine David Geffen School of Medicine at UCLA
University of Colorado VA Greater Los Angeles
Aurora, Colorado Los Angeles, California
Carl Schulman, MD Anthony D. Slonim, MD, DrPH

Director Professor of Medicine and Pediatrics
Department of Critical Care University of Nevada School of Medicine
University of Miami Miller School of Medicine President and CEO
Miami, Florida Renown Health
Reno, Nevada

Contributors xxix
Neel R. Sodha, MD Jean-Louis Teboul, MD, PhD

Assistant Professor of Surgery Professor of Medicine
Division of Cardiothoracic Surgery Medical Intensive Care Unit
Director Paris-South University
Lifespan Thoracic Aortic Center Bicêtre University Hospital
The Warren Alpert Medical School of Brown University Le Kremlin-Bicêtre, France
Providence, Rhode Island
Isaac Teitelbaum, MD
Vincenzo Squadrone, MD Professor of Medicine
Department of Anesthesia University of Colorado School of Medicine
Città della Salute e della Scienza Aurora, Colorado
Torino, Italy
Pierpaolo Terragni, MD
Roshni Sreedharan, MD Associate Professor
Clinical Assistant Professor Department of Surgical Sciences
Department of Anesthesiology and Center for Critical Care University of Sassari
Cleveland Clinic Lerner College of Medicine Sassari, Italy
Cleveland, Ohio
Stephen R. Thom, MD, PhD
Steven M. Steinberg, MD Professor
Professor of Surgery Department of Emergency Medicine
The Ohio State University University of Maryland School of Medicine
Columbus, Ohio Baltimore, Maryland
David M. Steinhorn, MD Elizabeth Thomas, DO

Professor of Pediatrics Assistant Professor
Department of Critical Care Department of Surgery
Children’s National Medical Center University of Florida
Washington, DC Gainesville, Florida
Nino Stocchetti, MD Jean-Francois Timsit, MD, PhD

Professor of Anesthesia Intensive Care Decision Sciences in Infectious Disease Prevention
Department of Physiopathology and Transplantation Paris Diderot University
Milan University Paris, France
Director
Neurosurgical Intensive Care Samuel A. Tisherman, MD, FACS, FCCM
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Professor
Milan, Italy Department of Surgery
R. A. Cowley Shock Trauma Center
Joerg-Patrick Stübgen, MB ChB, MD University of Maryland School of Medicine
Professor of Clinical Neurology Baltimore, Maryland
Weill Cornell Medicine of Cornell University
New York, New York S. Robert Todd, MD, FACS, FCCM
Associate Professor of Surgery
Joseph F. Sucher, MD Baylor College of Medicine
Vice Chairman of Surgery Chief
HonorHealth John C. Lincoln North Mountain Hospital General Surgery and Trauma
Director of Trauma Ben Taub Hospital
John C. Lincoln Deer Valley Hospital Houston, Texas
Phoenix, Arizona
Ashita J. Tolwani, MD, MSc
David Szpilman, MD Professor of Medicine
Medical Director Department of Medicine
Sociedade Brasileira de Salvamento Aquatico Division of Nephrology
Rio de Janeiro Civil Defense University of Alabama at Birmingham
Retired Director Birmingham, Alabama
Drowning Resuscitation Center
Retired Colonel
Fire Department of Rio de Janeiro—Lifeguard
Rio de Janeiro, Brazil

xxx Contributors
Antoni Torres, MD, FCCP Paul M. Vespa, MD, FCCM, FAAN, FANA, FNCS
Professor of Medicine (Pulmonology) Assistant Dean for Research in Critical Care Medicine
Universidad de Barcelona Gary L. Brinderson Family Chair in Neurocritical Care
Director Director of Neurocritical Care
Institut Clínic de Pneumologia i Cirurgia Toràcica Professor of Neurology and Neurosurgery
Hospital Clínic de Barcelona David Geffen School of Medicine at UCLA
Barcelona, Spain University of California Los Angeles
Cody D. Turner, MD
Department of Medicine Jean-Louis Vincent, MD, PhD
Division of Critical Care Professor of Intensive Care
Summa Akron City Hospital Université Libre de Bruxelles
Akron, Ohio Department of Intensive Care
Erasme Hospital
Krista Turner, MD Brussels, Belgium
Medical Director of Trauma
Department of Surgery Florian M.E. Wagenlehner, MD, PhD
The Medical Center of Aurora Professor of Urology
Aurora, Colorado Clinic for Urology, Pediatric Urology, and Andrology
Justus-Liebig-University
Edith Tzeng, MD Giessen, Germany
University of Pittsburgh Justin P. Wagner, MD
Chief of Vascular Surgery Resident
VA Pittsburgh Healthcare System Department of Surgery
Pittsburgh, Pennsylvania David Geffen School of Medicine at UCLA
Benoît Vallet, PhD
Professor of Anesthesiology and Critical Care Paul Phillip Walker, BMedSci (Hons), BM BS, MD
Lille University School of Medicine Consultant Physician
Lille University Hospital Respiratory Medicine
Lille, France University Hospital Aintree
Honorary Senior Lecturer
Greet Van den Berghe, MD, PhD Respiratory Research Department
Professor of Medicine University of Liverpool
Division of Intensive Care Medicine Liverpool, Great Britain
Katholieke Universiteit Leuven
Leuven, Belgium Keith R. Walley, MD
Professor
Arthur R.H. van Zanten, MD, PhD Department of Medicine
Hospital Medical Director University of British Columbia
Department of Intensive Care Vancouver, British Columbia, Canada
Gelderse Vallei Hospital
Ede, The Netherlands Robert J. Walter, MD
Brandywine Pediatrics
Floris Vanommeslaeghe, MD Wilmington, Delaware
Renal Division
Ghent University Hospital Kevin K.W. Wang, PhD
Ghent, Belgium Executive Director
Center for Neuroproteomics and Biomarker Research
Ramesh Venkataraman, AB Associate Professor
Consultant in Critical Care Medicine Department of Psychiatry
Academic Coordinator McKnight Brain Institute
Department of Critical Care University of Florida
Apollo Hospitals Gainesville, Florida
Chennai, India
Tisha Wang, MD
Kathleen M. Ventre, MD Associate Clinical Professor
Assistant Professor of Pediatrics Division of Pulmonary and Critical Care
University of Colorado School of Medicine David Geffen School of Medicine at UCLA
Children’s Hospital Colorado Los Angeles, California
Aurora, Colorado

Contributors xxxi
Nicholas S. Ward, MD Richard G. Wunderink, MD

Associate Professor of Medicine Professor of Medicine
Division of Critical Care, Pulmonary and Sleep Medicine Division of Pulmonary and Critical Care
The Warren Alpert Medical School at Brown University Northwestern University Feinberg School of Medicine
Providence, Rhode Island Medical Director, Medical ICU
Northwestern Memorial Hospital
Lorraine B. Ware, MD Chicago, Illinois
Professor of Medicine and Pathology, Microbiology, and
Immunology Christopher Wybourn, MD
Division of Allergy, Pulmonary, and Critical Care Medicine Trauma/Critical Care Fellow
Vanderbilt University School of Medicine Department of Surgery
Nashville, Tennessee University of California San Francisco
San Francisco General Hospital
Gregory A. Watson, MD, FACS San Francisco, California
Assistant Professor of Surgery and Critical Care
University of Pittsburgh School of Medicine Zhihui Yang, PhD
Pittsburgh, Pennsylvania Associate Scientific Director and Senior Scientist
Center for Neuroproteomics and Biomarkers Research
Lawrence R. Wechsler, MD Department of Psychiatry and Neuroscience
Henry B. Higman Professor and Chair University of Florida College of Medicine
Department of Neurology Gainesville, Florida
Pittsburgh, Pennsylvania Lonny Yarmus, DO
Wolfgang Weidner, MD, PhD Clinical Chief
Professor of Urology Division of Pulmonary and Critical Care
Clinic for Urology, Pediatric Urology, and Andrology Johns Hopkins University School of Medicine
Justus-Liebig-University Baltimore, Maryland
Giessen, Germany
Sachin Yende, MD, MS
Charles Weissman, MD Associate Professor
Professor and Chair Departments of Critical Care Medicine and Clinical and
Department of Anesthesiology and Critical Care Medicine Translational Sciences
Hadassah-Hebrew University Medical Center Director
Hebrew University—Hadassah School of Medicine Clinical Epidemiology Program
Jerusalem, Israel CRISMA Center
Mark H. Wilcox, MD Vice President
Professor and Head of Medical Microbiology Critical Care
University of Leeds Faculty of Medicine and Health VA Hospital Pittsburgh
Leeds General Infirmary NHS Trust Pittsburgh, Pennsylvania
Leeds, United Kingdom
Stephanie Grace Yi, MD
Keith M. Wille, MD, MSPH Abdominal Transplant Surgery Fellow
Associate Professor of Medicine Houston Methodist Hospital
Department of Internal Medicine Houston, Texas
Division of Pulmonary and Critical Care
University of Alabama Birmingham Dongnan Yu, MD
Birmingham, Alabama Attending Physician
Department of Anesthesiology
Michel Wolff, MD Guangdong General Hospital
Head Guangdong Academy of Medical Sciences
Medical and Infectious Diseases Intensive Care Guangzhou, Guangdong, China
Bichat-Claude Bernard Hospital
Paris, France Felix Yu, MD
Division of Pulmonary, Critical Care and Sleep Medicine
Tufts Medical Center
Boston, Massachusetts

xxxii Contributors
Roger D. Yusen, MD, MPH Allyson R. Zazulia, MD

Associate Professor of Medicine Associate Professor
Division of Pulmonary and Critical Care Medicine Departments of Neurology and Radiology
Washington University School of Medicine in St. Louis Associate Dean
St. Louis, Missouri Continuing Medical Education
Washington University
St. Louis, Missouri

CHAPTER xxxiii
PREFACE
We are pleased to bring you the Seventh Edition of Textbook of Critical the gap between medical and surgical intensive care practice. Unlike
Care. We’ve listened to our readers and have retained the acclaimed many critical care references, Textbook of Critical Care includes
features that have made this book one of the top sellers in critical pediatric topics, providing a comprehensive resource for our readers
care, while also making changes to the organization and content of who see a broad range of patients. We continue to focus on the multi-
the book to best reflect the changes in the critical care specialty since disciplinary approach to the care of critically ill patients and include
the last edition. contributors trained in anesthesia, surgery, pulmonary medicine,
Our tables, boxes, algorithms, diagnostic images, and key points, and pediatrics.
which provide clear and accessible information for quick reference, will The companion online book is more interactive than ever, with 29
continue to be featured prominently throughout the book. The Seventh procedural videos and 24 e-only procedural chapters, a powerful
Edition contains a wealth of new information, including an entirely search engine, hyperlinked references, and downloadable images. The
new section on Common Approaches for Organ Support, Diagnosis, website is mobile optimized for your convenience on all portable
and Monitoring. In addition, we have added new chapters on Extra- devices. Access to the online content is included with your book pur-
corporeal Membrane Oxygenation, Biomarkers of Acute Kidney chase, so please activate your e-book to take advantage of the full scope
Injury, Antimicrobial Stewardship, Targeted Temperature Manage- of information available to you.
ment and Therapeutic Hypothermia, Telemedicine in Intensive Care,
and many more. Given the increased use of bedside ultrasonography, Jean-Louis Vincent, MD, PhD
a new chapter addressing best practices with this now ubiquitous tool Edward Abraham, MD
has been added. All chapters throughout the book have been revised Frederick A. Moore, MD, MCCM
to reflect new knowledge in the field and, thus, changes in the practice Patrick M. Kochanek, MD, MCCM
of critical care medicine. Mitchell P. Fink, MD
Textbook of Critical Care has evolved with critical care practice over
the years and is now known as the reference that successfully bridges
xxxiii
IN MEMORIAM
MITCHELL P. FINK, MD
This edition of the Textbook of Critical Care is dedicated to the revising the textbook that served as the backbone for the Sixth
late Mitchell P. Fink, MD. Dr. Fink was Professor of Surgery and and this new Seventh Edition, which he also importantly helped
Vice Chair for Critical Care at the University of California Los to formulate. Mitch was a great friend and colleague to each of
Angeles and an international leader and giant in the field of us, and he will be dearly missed by us and by the entire field.
critical care medicine. He was the lead author of the Fifth We are confident that his visionary work on this book will serve,
Edition of this textbook. In the Fifth Edition, Dr. Fink inspired through its users, to improve the care and outcomes of critically
a novel, informative, user-friendly, and exciting approach to ill adults and children worldwide for many years into the future.

To my family and friends and all who can contribute to make a better world
— Jean-Louis Vincent
To Norma-May, my true love. To Claire and Erin, who bring me the greatest joy,
and to my mother, Dale Abraham, for her support throughout my life
— Edward Abraham
To my father, Ernest E. Moore, who was a family practitioner for 50 years in Butler,
Pennsylvania. He inspired me by his dedication to self-education, humility,
and service to his community
— Frederick A. Moore
To my family, friends, colleagues, and staff for their sacrifices, support, and
dedication, and to the late Dr. Peter Safar for inspiring each of us to bring promising
new therapies to the bedside of the critically ill
— Patrick M. Kochanek

1 Sudden Deterioration in Neurologic Status
Joseph M. Darby and Anupam Anupam
P
atients admitted to the intensive care unit (ICU) with critical stupor to coma) frequently represents the development of brain edema,
illness or injury are at risk for neurologic complications.1-5 A increasing intracranial pressure, new or worsening intracranial hemor-
sudden or unexpected change in the neurologic condition of a rhage, hydrocephalus, CNS infection, or cerebral vasospasm. In
critically ill patient often heralds a complication that may cause direct patients without a primary CNS diagnosis, an acute change in con-
injury to the central nervous system (CNS). Alternatively, such changes sciousness is often due to the development of infectious complications
may simply be neurologic manifestations of the underlying critical (i.e., sepsis-associated encephalopathy), drug toxicities, or the develop-
illness or treatment that necessitated ICU admission (e.g., sepsis). These ment or exacerbation of organ system failure. Nonconvulsive status
complications can occur in patients admitted to the ICU without neu- epilepticus is increasingly being recognized as a cause of impaired
rologic disease and in those admitted for management of primary CNS consciousness in critically ill patients (Box 1-1).44-53
problems (e.g., stroke). Neurologic complications can also occur as a States of altered consciousness manifesting as impairment in wake-
result of invasive procedures and therapeutic interventions performed. fulness or arousal (i.e., coma and stupor) and their causes are well
Commonly, recognition of neurologic complications is delayed or defined.42,43,54,55 Much confusion remains, however, regarding the diag-
missed entirely because ICU treatments (e.g., intubation, drugs) inter- nosis and management of delirium, perhaps the most common state
fere with the physical examination or confound the clinical picture. In of impaired CNS functioning in critically ill patients at large. When
other cases, neurologic complications are not recognized because of a dedicated instruments are used, delirium can be diagnosed in more
lack of sensitive methods to detect the problem (e.g., delirium). Mor- than 80% of critically ill patients, making this condition the most
bidity and mortality are increased among patients who develop neu- common neurologic complication of critical illness.56-58 Much of the
rologic complications; therefore, the intensivist must be vigilant in difficulty in establishing the diagnosis of delirium stems from the belief
evaluating all critically ill patients for changes in neurologic status. that delirium is a state characterized mainly by confusion and agitation
Despite the importance of neurologic complications of critical and that such states are expected consequences of the unique environ-
illness, few studies have specifically assessed their incidence and impact mental factors and sleep deprivation that characterize the ICU experi-
on outcome among ICU patients. Available data are limited to medical ence. Terms previously used to describe delirium in critically ill
ICU patients; data regarding neurologic complications in general sur- patients include ICU psychosis, acute confusional state, encephalopathy,
gical and other specialty ICU populations must be extracted from and postoperative psychosis. It is now recognized that ICU psychosis is
other sources. In studies of medical ICU patients, the incidence of a misnomer; delirium is a more accurate term.59
neurologic complications is 12.3% to 33%.1,2 Patients who develop Currently accepted criteria for the diagnosis of delirium include
neurologic complications have increased morbidity, mortality, and abrupt onset of impaired consciousness, disturbed cognitive func-
ICU length of stay. Sepsis is the most common problem associated with tion, fluctuating course, and presence of a medical condition that
development of neurologic complications (sepsis-associated encepha- could impair brain function.60 Subtypes of delirium include hyperac-
lopathy). In addition to encephalopathy, other common neurologic tive (agitated) delirium and the more common hypoactive or quiet
complications associated with critical illness include seizures and delirium.58 Impaired consciousness may be apparent as a reduction
stroke. As the complexity of ICU care has increased, so has the risk of in awareness, psychomotor retardation, agitation, or impairment in
neurologic complications. Neuromuscular disorders are now recog- attention (increased distractibility or vigilance). Cognitive impairment
nized as a major source of morbidity in severely ill patients.6 Recog- can include disorientation, impaired memory, and perceptual aber-
nized neurologic complications occurring in selected medical, surgical, rations (hallucinations or illusions).61 Autonomic hyperactivity and
and neurologic ICU populations are shown in Table 1-1.7-41 sleep disturbances may be features of delirium in some patients (e.g.,
those with drug withdrawal syndromes, delirium tremens). Delirium
in critically ill patients is associated with increased morbidity, mor-
IMPAIRMENT IN CONSCIOUSNESS tality, and ICU length of stay.62-64 In general, sepsis and medications
Global changes in CNS function, best described in terms of impair- should be the primary etiologic considerations in critically ill patients
ment in consciousness, are generally referred to as encephalopathy or who develop delirium.
altered mental status. An acute change in the level of consciousness, As has been noted, nonconvulsive status epilepticus is increasingly
undoubtedly, is the most common neurologic complication that occurs recognized as an important cause of impaired consciousness in criti-
after ICU admission. Consciousness is defined as a state of awareness cally ill patients. Although the general term can encompass other enti-
(arousal or wakefulness) and the ability to respond appropriately to ties, such as absence and partial complex seizures, in critically ill
changes in environment.42 For consciousness to be impaired, global patients, nonconvulsive status epilepticus is often referred to as status
hemispheric dysfunction or dysfunction of the brainstem reticular epilepticus of epileptic encephalopathy.53 It is characterized by alteration
activating system must be present.43 Altered consciousness may result in consciousness or behavior associated with electroencephalographic
in a sleeplike state (coma) or a state characterized by confusion and evidence of continuous or periodic epileptiform activity without overt
agitation (delirium). States of acutely altered consciousness seen in the motor manifestations of seizures. In a study of comatose patients
critically ill are listed in Table 1-2. without overt seizure activity, nonconvulsive status epilepticus was
When an acute change in consciousness is noted, the patient should evident in 8% of subjects.51 Nonconvulsive status epilepticus can
be evaluated, keeping in mind the patient’s age, presence or absence of precede or follow an episode of generalized convulsive status epilepti-
coexisting organ system dysfunction, metabolic status and medication cus; it can also occur in patients with traumatic brain injury, subarach-
list, and presence or absence of infection. In patients with a primary noid hemorrhage, global brain ischemia or anoxia, sepsis, and multiple
CNS disorder, deterioration in the level of consciousness (e.g., from organ failure. Despite the general consensus that nonconvulsive status
2
CHAPTER 1 Sudden Deterioration in Neurologic Status 3
TABLE 1-1 Neurologic Complications in Selected Specialty Populations
MEDICAL
Bone marrow transplantation7,8 CNS infection, stroke, subdural hematoma, brainstem ischemia, hyperammonemia, Wernicke encephalopathy
Cancer9 Stroke, intracranial hemorrhage, CNS infection
Fulminant hepatic failure10 Encephalopathy, coma, brain edema, increased ICP
HIV/AIDS11,12 Opportunistic CNS infection, stroke, vasculitis, delirium, seizures, progressive multifocal leukoencephalopathy
Pregnancy13,14 Seizures, ischemic stroke, cerebral vasospasm, intracranial hemorrhage, cerebral venous thrombosis, hypertensive encephalopathy,
pituitary apoplexy
SURGICAL
Cardiac surgery15-19 Stroke, delirium, brachial plexus injury, phrenic nerve injury
Vascular surgery20,21
Carotid Stroke, cranial nerve injuries (recurrent laryngeal, glossopharyngeal, hypoglossal, facial), seizures
Aortic Stroke, paraplegia
Peripheral Delirium
Transplantation10,22-25
Heart Stroke
Liver Encephalopathy, seizures, opportunistic CNS infection, intracranial hemorrhage, Guillain-Barré syndrome, central pontine
myelinolysis
Renal Stroke, opportunistic CNS infection, femoral neuropathy
Urologic surgery (TURP)26 Seizures and coma (hyponatremia)
Otolaryngologic surgery27,28 Recurrent laryngeal nerve injury, stroke, delirium
Orthopedic surgery29
Spine Myelopathy, radiculopathy, epidural abscess, meningitis
Knee and hip replacement Delirium (fat embolism)
Long-bone fracture/nailing Delirium (fat embolism)
NEUROLOGIC
Stroke30-34 Stroke progression or extension, reocclusion after thrombolysis, bleeding, seizures, delirium, brain edema, herniation
Intracranial surgery35 Bleeding, edema, seizures, CNS infection
Subarachnoid hemorrhage32,36-38 Rebleeding, vasospasm, hydrocephalus, seizures
Traumatic brain injury32,39,40 Intracranial hypertension, bleeding, seizures, stroke (cerebrovascular injury), CNS infection
Cervical spinal cord injury41 Ascension of injury, stroke (vertebral artery injury)
CNS, central nervous system; HIV/AIDS, human immunodeficiency virus/acquired immunodeficiency syndrome; ICP, intracranial pressure; TURP, transurethral prostatic resection.
States of Acutely Altered perioperative stroke ranges from 0.3% to 3.5%.67 Patients undergoing
TABLE 1-2 cardiac or vascular surgery and surgical patients with underlying cere-
Consciousness
brovascular disease can be expected to have an increased risk of peri-
operative stroke.19
STATE DESCRIPTION The frequency of new or worsening focal neurologic deficits in
Coma Closed eyes, sleeplike state with no response to external stimuli patients admitted with a primary neurologic or neurosurgical disorder
(pain) varies. For example, as many as 30% of patients with aneurysmal sub-
Stupor Responsive only to vigorous or painful stimuli arachnoid hemorrhage develop delayed ischemic neurologic deficits.36
Patients admitted with stroke often develop worsening or new symp-
Lethargy Drowsy, arouses easily and appropriately to stimuli
toms as a result of stroke progression, bleeding, or reocclusion of
Delirium Acute state of confusion with or without behavioral disturbance vessels previously opened with interventional therapy. In patients who
Catatonia Eyes open, unblinking, unresponsive have undergone elective intracranial surgery, postsurgical bleeding or
infectious complications are the main causes of new focal deficits. In
trauma patients, unrecognized injuries to the cerebrovascular circula-
tion can cause new deficits. Patients who have sustained spinal cord
injuries, and those who have undergone surgery of the spine or of the
epilepticus is a unique entity responsible for impaired consciousness thoracic or abdominal aorta, can develop worsening or new symptoms
in some critically ill patients, there is no general consensus on the of spinal cord injury. Early deterioration of CNS function after spinal
electroencephalographic criteria for its diagnosis or the optimal cord injury usually occurs as a consequence of medical interventions
approach to treatment.65 to stabilize the spine, whereas late deterioration is usually due to hypo-
tension and impaired cord perfusion. Occasionally, focal weakness or
STROKE AND OTHER FOCAL sensory symptoms in the extremities occur as a result of occult brachial
plexus injury or compression neuropathy. New cranial nerve deficits
NEUROLOGIC DEFICITS in patients without primary neurologic problems can occur after neck
The new onset of a major neurologic deficit that manifests as a focal surgery or carotid endarterectomy.
impairment in motor or sensory function (e.g., hemiparesis) or one
that results in seizures usually indicates a primary problem referable
to the cerebrovascular circulation. In a study evaluating the value of
SEIZURES
computed tomography (CT) in medical ICU patients, ischemic stroke The new onset of motor seizures occurs in 0.8% to 4% of critically ill
and intracranial bleeding were the most common abnormalities associ- medical ICU patients.1,2,68 New-onset seizures in general medical-
ated with the new onset of a neurologic deficit or seizures.66 Overall, surgical ICU patients is typically caused by narcotic withdrawal, hypo-
the frequency of new-onset stroke is between 1% and 4% in medical natremia, drug toxicities, or previously unrecognized structural
ICU patients.1,2 Among general surgical patients, the frequency of abnormalities.3,68 New stroke, intracranial bleeding, and CNS infection

4 PART 1 Common Problems
General Causes of Acutely Impaired are other potential causes of seizures after ICU admission. The fre-
BOX 1-1 quency of seizures is higher in patients admitted to the ICU with a
Consciousness in the Critically Ill
primary neurologic problem such as traumatic brain injury, aneurys-
INFECTION mal subarachnoid hemorrhage, stroke, or CNS infection.69 Because
Sepsis encephalopathy nonconvulsive status epilepticus may be more common than was pre-
CNS infection viously appreciated, this problem should also be considered in the
differential diagnosis of patients developing new, unexplained, or pro-
DRUGS
Narcotics longed alterations in consciousness.
Benzodiazepines
Anticholinergics GENERALIZED WEAKNESS AND
Anticonvulsants
Tricyclic antidepressants
NEUROMUSCULAR DISORDERS
Selective serotonin uptake inhibitors Generalized muscle weakness often becomes apparent in ICU patients
Phenothiazines as previous impairments in arousal are resolving or sedative and neu-
Steroids romuscular blocking agents are being discontinued or tapered. Poly-
Immunosuppressants (cyclosporine, FK506, OKT3)
neuropathy and myopathy associated with critical illness are now well
Anesthetics
recognized as the principal causes of new-onset generalized weakness
ELECTROLYTE AND ACID-BASE DISTURBANCES among ICU patients being treated for nonneuromuscular disor-
Hyponatremia ders.5,70-73 These disorders also may be responsible for prolonged ven-
Hypernatremia
tilator dependency in some patients. Patients at increased risk for these
Hypercalcemia
Hypermagnesemia complications include those with sepsis, systemic inflammatory
Severe acidemia and alkalemia response syndrome, and multiple organ dysfunction syndrome, as well
as those who require prolonged mechanical ventilation. Other risk
ORGAN SYSTEM FAILURE
factors include treatment with corticosteroids or neuromuscular
Shock
Renal failure blocking agents. In contrast to demyelinating neuropathies (e.g.,
Hepatic failure Guillain-Barré syndrome), critical illness polyneuropathy is primarily
Pancreatitis an axonal condition. Critical illness polyneuropathy is diagnosed in a
Respiratory failure (hypoxia, hypercapnia) high percentage of patients undergoing careful evaluation for weakness
ENDOCRINE DISORDERS acquired while in the ICU. Because primary myopathy coexists in a
Hypoglycemia large number of patients with critical illness polyneuropathy, ICU-
Hyperglycemia acquired paresis72 or critical illness neuromuscular abnormalities5 may
Hypothyroidism be better terms to describe this problem. Although acute Guillain-
Hyperthyroidism Barré syndrome and myasthenia gravis are rare complications of criti-
Pituitary apoplexy cal illness, these diagnoses should also be considered in patients who
DRUG WITHDRAWAL develop generalized weakness in the ICU.
Alcohol
Opiates NEUROLOGIC COMPLICATIONS OF
Barbiturates
Benzodiazepines PROCEDURES AND TREATMENTS
VASCULAR CAUSES Routine procedures performed in the ICU or in association with evalu-
Shock ation and treatment of critical illness can result in neurologic complica-
Hypotension tions.4 The most obvious neurologic complications are those associated
Hypertensive encephalopathy with intracranial bleeding secondary to the treatment of stroke and
CNS vasculitis other disorders with thrombolytic agents or anticoagulants. Other
Cerebral venous sinus thrombosis
notable complications are listed in Table 1-3.
CNS DISORDERS
Hemorrhage
Stroke
EVALUATION OF SUDDEN
Brain edema NEUROLOGIC CHANGE
Hydrocephalus
Increased intracranial pressure A new or sudden change in the neurologic condition of a critically ill
Meningitis patient necessitates a focused neurologic examination, review of the
Ventriculitis clinical course and medications administered before the change, a
Brain abscess thorough laboratory assessment, and appropriate imaging or neuro-
Subdural empyema physiologic studies when indicated. The type and extent of the evalu-
Seizures ation depend on clinical context and the general category of neurologic
Vasculitis change occurring. The history and physical examination should lead
SEIZURES the clinician to the diagnostic approach best suited to the individual
Convulsive and nonconvulsive status epilepticus patient.
MISCELLANEOUS Essential elements of the neurologic examination include an assess-
Fat embolism syndrome ment of the level and content of consciousness, pupillary size and
Neuroleptic malignant syndrome reactivity, and motor function. Additional evaluation of the cranial
Thiamine deficiency (Wernicke encephalopathy) nerves and peripheral reflexes and a sensory examination are con-
Psychogenic unresponsiveness ducted as indicated by the clinical circumstances. If the patient is
comatose on initial evaluation, a more detailed coma examination
CNS, central nervous system.
should be performed to help differentiate structural from metabolic
causes of coma.43,55 When the evaluation reveals only a change in
arousal without evidence of a localizing lesion in the CNS, a search for
infection, discontinuation or modification of drug therapy, and a

CHAPTER 1 Sudden Deterioration in Neurologic Status 5
Neurologic Complications Associated when the diagnosis of nonconvulsive status epilepticus is being enter-
TABLE 1-3 tained. Continuous electroencephalography should be considered
with ICU Procedures and Treatments
when the index of suspicion for nonconvulsive status epilepticus
remains high and the initial electroencephalographic studies are
PROCEDURE COMPLICATION
unrevealing.
Angiography Cerebral cholesterol emboli syndrome Computed tomography (CT) is indicated for nonneurologic
Anticoagulants/antiplatelet Intracranial bleeding patients with new focal deficits, seizures, or otherwise unexplained
agents impairments in arousal.66 In patients with primary neurologic disor-
Arterial catheterization Cerebral embolism ders, CT is indicated if worsening brain edema, herniation, bleeding,
and hydrocephalus are considerations when new deficits or worsening
Bronchoscopy Increased ICP
neurologic status occurs. In some cases, when the basis for a change
Central venous Cerebral air embolism, carotid dissection, in neurologic condition remains elusive, magnetic resonance imaging
catheterization Horner’s syndrome, phrenic nerve injury, (MRI) may be helpful. In particular, the diffusion-weighted MRI tech-
brachial plexus injury, cranial nerve injury
nique can reveal structural abnormalities such as hypoxic brain injury,
DC cardioversion Embolic stroke, seizures fat embolism, vasculitis, cerebral venous thrombosis, or multiple
Dialysis Seizures, increased ICP (dialysis disequilibrium infarcts following cardiopulmonary bypass that are not apparent by
syndrome) standard CT or conventional MRI.75-80 MRI may be the imaging modal-
Endovascular procedures Vessel rupture, thrombosis, reperfusion bleeding ity of choice in patients with human immunodeficiency virus (HIV)
(CNS) and new CNS complications.75 For patients who develop signs and
Epidural catheter Spinal epidural hematoma, epidural abscess symptoms of spinal cord injury complicating critical illness, MRI or
ICP monitoring CNS infection (ventriculitis), hemorrhage somatosensory evoked potentials can be used to further delineate the
nature and severity of the injury. For patients who develop generalized
Intraaortic balloon pump Lower extremity paralysis
muscle weakness or unexplained ventilator dependency, electromyog-
Intubation Spinal cord injury raphy and nerve conduction studies can confirm the presence of criti-
Left ventricular assist Stroke, seizures cal illness polyneuropathy or myopathy.
devices
Lumbar puncture or drain Meningitis, herniation MONITORING FOR
Mechanical ventilation Cerebral air embolism, increased ICP (high PEEP NEUROLOGIC CHANGES
and hypercapnia), seizures (hypocapnia)
Nasogastric intubation Intracranial placement
The common occurrence of neurologic changes in critically ill patients
emphasizes the need for vigilant monitoring. A variety of clinical tech-
CNS, central nervous system; DC, direct current; ICP, intracranial pressure; ICU, intensive care niques such as the Glasgow Coma Scale, National Institutes of Health
unit; PEEP, positive end-expiratory pressure. Stroke Scale, Ramsay Sedation Scale, Richmond Agitation-Sedation
Scale, and Confusion Assessment Method for the Intensive Care Unit
(CAM-ICU) can be used to monitor clinical neurologic status.57,58,81-86
Neurophysiologic methods such as the bispectral index may provide
general metabolic evaluation may be indicated. Lumbar puncture to more objective neurologic monitoring in the future for patients admit-
aid the diagnosis of CNS infection may be warranted in selected neu- ted to the ICU with and without primary neurologic problems.87-89 For
rosurgical patients and immunocompromised individuals. Lumbar patients admitted to the ICU with a primary neurologic disorder, a
puncture to rule out nosocomially acquired meningitis in other variety of monitoring techniques including measurements of intra-
patients is generally not rewarding.74 Electroencephalography should cranial pressure, near-infrared spectroscopy, brain tissue Po2, transcra-
be performed in patients with clear evidence of seizures, as well as nial Doppler, and electroencephalography are available.90
ANNOTATED REFERENCES
De Jonghe B, Sharshar T, Lefaucheur JP, et al. Paresis acquired in the intensive care unit. A prospective In an effort to dispel the myth that environmental conditions lead to “ICU psychosis,” the authors of this
multicenter study. JAMA 2002;288:2859–2867. article argue that ICU psychosis is more appropriately described as delirium. The etiology and
This prospective multicenter study of critically ill patients was the first to assess the clinical incidence, management of delirium in critically ill patients are reviewed.
risk factors, and outcomes of mechanically ventilated patients developing ICU-acquired weakness, Naik-Tolani S, Oropello JM, Benjamin E. Neurologic complications in the intensive care unit. Clin Chest
emphasizing a central role for corticosteroid use in its genesis and prolonged mechanical ventilation Med 1999;20:423–434.
as a relevant ICU outcome. The authors of this article present an overview of central nervous system (CNS) complications of critical
Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients. Validity and reliability illness and ICU procedures in critically ill patients without primary disorders of the CNS.
of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). JAMA Sundgren PC, Reinstrup P, Romner B, et al. Value of conventional diffusion- and perfusion-weighted MRI
2001;286:2703–2710. in the management of patients with unclear cerebral pathology, admitted to the intensive care unit.
Recognizing that the diagnosis of delirium is often difficult in the critically ill patient receiving mechani- Neuroradiology 2002;44:674–680.
cal ventilation, the authors adapted a common method for assessing delirium using the Confusion This retrospective study of 21 critically ill patients undergoing MRI because of a disparity in clinical
Assessment Method to critically ill patients receiving mechanical ventilation. This prospective neurologic findings and CT imaging revealed that additional useful diagnostic and prognostic
evaluation revealed high sensitivity, specificity, and inter-rater reliability in detecting delirium in information can be obtained, especially when diffusion- and perfusion-weighted MR sequences are
80% of the patient population they studied. obtained.
McGuire BE, Basten CJ, Ryan CJ, et al. Intensive care unit syndrome. A dangerous misnomer. Arch Intern
Med 2000;160:906–909.
References for this chapter can be found at expertconsult.com.

CHAPTER 1 Sudden Deterioration in Neurologic Status 5.e1
REFERENCES
1. Isensee LM, Weiner LJ, Hart RG. Neurologic disorders in a medical intensive care unit. J Crit Care 49. Kaplan PW. Assessing the outcomes in patients with nonconvulsive status epilepticus: nonconvulsive
1989;4:208–210. status epilepticus is underdiagnosed, potentially overtreated, and confounded by comorbidity. J Clin
2. Bleck TP, Smith MC, Pierre-Louis SJ, et al. Neurologic complications of critical medical illnesses. Neurophysiol 1999;16:341–352.
Crit Care Med 1993;21:98–103. 50. Vespa PM, Nuwer MR, Nenov V, et al. Increased incidence and impact of nonconvulsive and con-
3. Wijdicks EF. Neurologic complications in critically ill patients. Anesth Analg 1996;83:411–419. vulsive seizures after traumatic brain injury as detected by continuous electroencephalographic
4. Naik-Tolani S, Oropello JM, Benjamin E. Neurologic complications in the intensive care unit. monitoring. J Neurosurg 1999;91:750–760.
Clin Chest Med 1999;20:423–434. 51. Towne AR, Waterhouse EJ, Boggs JG, et al. Prevalence of nonconvulsive status epilepticus in comatose
5. Barlas I, Oropello JM, Benjamin E. Neurologic complications in intensive care. Curr Opin Crit Care patients. Neurology 2000;54:340–345.
2001;7:68–73. 52. Dennis LJ, Classen J, Hirsch LJ, et al. Nonconvulsive status epilepticus after subarachnoid hemor-
6. Lorin S, Nierman DM. Critical illness neuromuscular abnormalities. Crit Care Clin 2002;18: rhage. Neurosurgery 2002;51:1136–1143.
553–568. 53. Ruegg SJ, Dichter MA. Diagnosis and treatment of nonconvulsive status epilepticus in an intensive
7. Coplin WM, Cochran MS, Levine SR, et al. Stroke after bone marrow transplantation: frequency, care unit setting. Curr Treat Options Neurol 2003;5:93–110.
aetiology and outcome. Brain 2001;124:1043–1051. 54. Liao YJ, So YT. An approach to critically ill patients in coma. West J Med 2002;176:184–187.
8. Sostak P, Padovan CS, Yousry TA, et al. Prospective evaluation of neurological complications after 55. Malik K, Hess DC. Evaluating the comatose patient: rapid neurologic assessment is key to appropriate
allogeneic bone marrow transplantation. Neurology 2003;60:842–848. management. Postgrad Med 2002;111:38–55.
9. Rogers LR. Cerebrovascular complications in cancer patients. Neurol Clin 2003;21:167–192. 56. Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: Validity and
10. Krasko A, Deshpande K, Bonvino S. Liver failure, transplantation and critical care. Crit Care Clin reliability of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). JAMA
2003;19:155–183. 2001;286:2703–2710.
11. Said G, Saimont AG, Lacroix C. Neurologic complications of HIV and AIDS. Philadelphia: 57. Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically ill patients: validation of the
WB Saunders; 1998. Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med 2001;29:
12. Treisman GJ, Kaplin AI. Neurologic and psychiatric complications of antiretroviral agents. AIDS 1481–1483.
2002;16:1201–1215. 58. Ely EW, Siegel MD, Inouye S. Delirium in the intensive care unit: an under-recognized syndrome of
13. Fox MW, Harms RW, Davis DH. Selected neurologic complications of pregnancy. Mayo Clin Proc organ dysfunction. Semin Resp Crit Care Med 2001;22:115–126.
1990;65:1595–1618. 59. McGuire BE, Basten CJ, Ryan CJ, et al. Intensive care unit syndrome: a dangerous misnomer.
14. Lanska DJ, Kryscio RJ. Peripartum stroke and intracranial venous thrombosis in the National Hos- Arch Intern Med 2000;160:906–909.
pital Discharge Survey. Obstet Gynecol 1997;89:413–418. 60. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed.
15. Roach GW, Kanchuger M, Mangano CM, et al. Adverse cerebral outcomes after coronary bypass Washington, DC: American Psychiatric Association; 1994.
surgery: Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and 61. Lipowski ZJ. Delirium (acute confusional states). JAMA 1987;258:1789–1792.
Education Foundation Investigators. N Engl J Med 1996;335:1857–1863. 62. Rutherford LE, Sessler CN, Levenson JL, et al. Prospective evaluation of delirium and agitation in a
16. Hogue CW, Murphy SF, Schechtman KB, et al. Risk factors for early or delayed stroke after cardiac medical intensive care unit. Crit Care Med 1991;19(suppl):S81.
surgery. Circulation 1999;100:642–647. 63. Sessler CN, Rutherford L, Best A, et al. Agitation in a medical intensive care unit: prospective analysis
17. Arrowsmith JE, Grocott HP, Reves JG, et al. Central nervous system complications of cardiac surgery. of incidence and risk factors. Chest 1992;102(suppl):91S.
Br J Anaesth 2000;84:378–393. 64. Ely EW, Gautam S, Margolin R, et al. The impact of delirium in the intensive care unit on hospital
18. Hogue CW, Barzilai B, Pieper KS, et al. Sex differences in neurologic outcomes and mortality length of stay. Intensive Care Med 2001;27:1892–1900.
after cardiac surgery: a Society of Thoracic Surgery national database report. Circulation 2001;103: 65. Brenner RP. Is it status? Epilepsia 2002;43(suppl 3):103–113.
2133–2137. 66. Rafanan AL, Kakulavar P, Perl J, et al. Head computed tomography in medical intensive care unit
19. McKhann GM, Grega MA, Borowicz LM, et al. Encephalopathy and stroke after coronary bypass patients: clinical indications. Crit Care Med 2000;28:1306–1309.
grafting. Arch Neurol 2002;59:1422–1428. 67. Bell R, Merli G. Perioperative assessment and management of the surgical patient with neurologic
20. Alpagut U, Dayioglu E. Anterior spinal artery syndrome after infrarenal abdominal aortic surgery. problems. In: Merli G, Weitz H. Medical management of the surgical patient. Philadelphia: Saunders;
J Cardiovasc Surg (Torino) 2002;43:865–868. 1998. p. 283–311.
21. Gopalan PD, Burrows RC. Critical care of the vascular surgery patient. Crit Care Clin 2003;19: 68. Wijdicks EF, Sharbrough FW. New onset seizures in critically ill patients. Neurology 1993;43:
109–125. 1042–1044.
22. Patchell RA. Neurological complications of organ transplantation. Ann Neurol 1994;36:688– 69. Herman ST. Epilepsy after brain insult: targeting epileptogenesis. Neurology 2002;59(9 suppl
703. 5):S521–S526.
23. Bronster DJ, Emre S, Boccagni P, et al. Central nervous system complications in liver transplant 70. Lacomis D, Petrella JT, Giuliani MJ. Causes of neuromuscular weakness in the intensive care unit: a
recipients—incidence, timing, and long-term follow-up. Clin Transplant 2000;14:1–7. study of ninety-two patients. Muscle Nerve 1998;21:610–617.
24. Liang BC. Neurologic complications of orthotopic liver transplantation. Hosp Physician 2000;36: 71. Hund E. Neurological complications of sepsis: critical illness polymyopathy and myopathy. J Neurol
43–46. 2001;248:929–934.
25. Oliveras A, Roquer J, Puig JM, et al. Stroke in renal transplant recipients: epidemiology, predictive 72. De Jonghe B, Sharshar T, Lefaucheur JP, et al. Paresis acquired in the intensive care unit: a prospective
risk factors and outcome. Clin Transplant 2003;17:1–8. multicenter study. JAMA 2002;288:2859–2867.
26. Leung AKH, Tan IK. Critical care and the urologic patient. Crit Care Clin 2003;19:1–10. 73. Marinelli WA, Leatherman JW. Neuromuscular disorders in the intensive care unit. Crit Care Clin
27. Bansal A, Miskoff J, Lis RJ. Otolarynogologic critical care. Crit Care Clin 2003;19:55–72. 2002;18:915–929.
28. Garantziotis S, Kyrmizakis DE, Liolios AD. Critical care of the head and neck patient. Crit Care Clin 74. Metersky ML, Williams A, Rafanan AL. Retrospective analysis: are fever and altered mental status
2003;19:73–90. indications for lumbar puncture in a hospitalized patient who has not undergone neurosurgery?
29. Nazon D, Abergel G, Hatem CM. Critical care in orthopedic and spine surgery. Crit Care Clin Clin Infect Dis 1997;25:285–288.
2003;19:33–53. 75. Soulen RL, Duman RJ, Hoeffner E. Magnetic resonance imaging in the critical care setting. Crit Care
30. Grotta JC, Welch KM, Fagan SC, et al. Clinical deterioration following improvement in the NINDS Clin 1994;10:401–416.
rt-PA Stroke Trial. Stroke 2001;32:661–668. 76. Arbelaez A, Castillo M, Mukherji SK. Diffusion-weighted MR imaging of global cerebral anoxia.
31. Qureshi AI, Tuhrim S, Broderick JP, et al. Spontaneous intracranial hemorrhage. N Engl J Med AJNR Am J Neuroradiol 1999;20:999–1007.
2001;344:1450–1460. 77. Parizel PM, Demey HE, Veeckmans G, et al. Early diagnosis of cerebral fat embolism syndrome by
32. Fahy BG, Sivaraman V. Current concepts in neurocritical care. Anesth Clin North Am 2002;20: diffusion-weighted MRI (starfield pattern). Stroke 2001;32:2942–2944.
441–462. 78. Lovblad KO, Bassetti C, Schneider J, et al. Diffusion-weighted MR in cerebral venous thrombosis.
33. Ferro JM, Caeiro L, Verdelho A. Delirium in acute stroke. Curr Opin Neurol 2002;15:51–55. Cerebrovasc Dis 2001;11:169–176.
34. Sumer M, Ozdemir I, Erturk O. Progression in acute ischemic stroke: frequency, risk factors, and 79. Wityk RJ, Goldsborough MA, Hillis A, et al. Diffusion- and perfusion-weighted brain magnetic
prognosis. J Clin Neurosci 2003;10:177–180. imaging in patients with neurologic complications after cardiac surgery. Arch Neurol 2001;58:
35. Kelly DF. Neurosurgical postoperative care. Neurosurg Clin N Am 1994;5:789–810. 571–576.
36. Kassell NF, Sasaki T, Colohan AR, et al. Cerebral vasospasm following aneurysmal subarachnoid 80. Sundgren PC, Reinstrup P, Romner B, et al. Value of conventional, and diffusion and perfusion
hemorrhage. Stroke 1985;16:562–572. weighted MRI in the management of patients with unclear cerebral pathology, admitted to the
37. Kirsch JR, Diringer MN, Borel CO, et al. Cerebral aneurysms: mechanisms of injury and critical care intensive care unit. Neuroradiology 2002;44:674–680.
interventions. Crit Care Clin 1989;5:755–772. 81. Brain Trauma Foundation, American Association of Neurological Surgeons, Joint Section on Neu-
38. Tamargo RJ, Walter KA, Oshiro EM. Aneurysmal subarachnoid hemorrhage: prognostic features and rotrauma and Critical Care. Glasgow Coma Scale score. J Neurotrauma 2000;17:563–571.
outcomes. New Horiz 1997;5:364–375. 82. DeJonghe B, Cook D, Apepere-De-Vecchi C, et al. Using and understanding sedation scoring systems:
39. Chesnut RM. Secondary brain insults after head injury: clinical perspectives. New Horiz 1995;3: a systematic review. Intensive Care Med 2000;26:275–285.
366–375. 83. Bergeron N, Dubois MJ, Dumont M, et al. Intensive care delirium screening checklist: evaluation of
40. Pilitsis JG, Rengachary SS. Complications of head injury. Neurol Res 2001;23:227–236. a new screening tool. Intensive Care Med 2001;27:859–864.
41. Harrop JS, Sharan AD, Vaccaro AR, et al. The cause of neurologic deterioration after acute cervical 84. Sessler CN, Gosnell MS, Gnap M, et al. The Richmond agitation-sedation scale: validity and reliability
spinal cord injury. Spine 2001;26:340–346. in adult intensive care unit patients. Am J Resp Crit Care Med 2002;166:1338–1344.
42. Cartilidge N. States related to or confused with coma. J Neurol Neurosurg Psychiatry 2001;71(suppl 85. Adams HP, Adams RJ, Brott T, et al. Guideline for the early management of patients with ischemic
1):i18–i19. stroke. Stroke 2003;34:1056–1083.
43. Plum F, Posner J. The diagnosis of stupor and coma, 3rd ed. Philadelphia: FA Davis; 1980. 86. Ely EW, Truman B, Shintani A, et al. Monitoring sedation status over time in ICU patients: reliability
44. Lowenstein DH, Aminoff MJ. Clinical and EEG features of status epilepticus in comatose patients. and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA 2003;289:2983–2991.
Neurology 1992;42:100–104. 87. Simmons LE, Riker RR, Prato S, et al. Assessing sedation during intensive care unit mechanical
45. Drislane FW. Nonconvulsive status epilepticus in patients with cancer. Clin Neurol Neurosurg ventilation with the bispectral index and the sedation-agitation scale. Crit Care Med 1999;27:
1994;96:314–318. 1499–1504.
46. DeLorenzo RJ, Waterhouse EJ, Towne AR, et al. Persistent nonconvulsive status epilepticus after 88. Gilbert TT, Wagner MR, Halukurike V, et al. Use of bispectral electroencephalogram monitoring to
control of convulsive status epilepticus. Epilepsia 1998;39:833–840. assess neurologic status in unsedated, critically ill patients. Crit Care Med 2001;29:2036–2037.
47. Litt B, Wityk RJ, Hertz SH, et al. Nonconvulsive status epilepticus in the critically ill elderly. Epilepsia 89. Mondello E, Siliotti R, Noto G, et al. Bispectral index in ICU: correlation with Ramsay score on
1998;39:1194–1202. assessment of sedation level. J Clin Monit Comput 2002;17:271–277.
48. Jordan KG. Nonconvulsive status epilepticus in acute brain injury. J Clin Neurophysiol 1999;16: 90. Gupta AK. Monitoring the injured brain in the intensive care unit. J Postgrad Med 2002;48:
332–340. 218–225.

2 Agitation and Delirium
Kwame Frimpong, E. Wesley Ely, and Arna Banerjee
A
gitation and delirium are commonly encountered in the inten- have been used to describe this condition.16 Delirium can be clas-
sive care unit (ICU). They are more than just an inconvenience; sified according to psychomotor behavior into hypoactive delirium,
these conditions can have deleterious effects on patient and staff hyperactive delirium, or a mixed subtype. Hypoactive delirium,
safety and contribute to poor outcomes. It is therefore important for which is the most prevalent form of delirium, is characterized by
clinicians to be able to recognize agitation and delirium and to have decreased physical and mental activity and inattention. In contrast,
an organized approach for its evaluation and management. hyperactive delirium is characterized by combativeness and agita-
tion. Patients with both features have mixed delirium.17-19 Hyperactive
delirium puts both patients and caregivers at risk of serious injury
AGITATION but fortunately only occurs in a minority of critically ill patients.17-19
Agitation is a psychomotor disturbance characterized by excessive Hypoactive delirium might actually be associated with a worse prog-
motor activity associated with a feeling of inner tension.1,3 The activity nosis.20,21 The Delirium Motor Subtype Scale may assist in making this
is usually nonproductive and repetitious, consisting of behaviors such diagnosis.22
as pacing, fidgeting, wringing of hands, pulling of clothes, and an Although healthcare professionals realize the importance of recog-
inability to sit still. Careful observation of the patient may reveal the nizing delirium, it frequently goes unrecognized in the ICU.23-30 Even
underlying intent. In the ICU, agitation is frequently related to anxiety when ICU delirium is recognized, most clinicians consider it an
or delirium. Agitation may be caused by various factors: metabolic expected event that is often iatrogenic and without consequence.23
disorders (hypo- and hypernatremia), hyperthermia, hypoxia, hypo- However, it needs to be viewed as a form of organic brain dysfunction
tension, use of sedative drugs and/or analgesics, sepsis, alcohol with- that has consequences if left undiagnosed and untreated.
drawal, and long-term psychoactive drug use to name a few.4,5 It can
also be caused by external factors such as noise, discomfort, and pain.6
Associated with a longer length of stay in the ICU and higher costs,4
Risk Factors for Delirium
agitation can be mild, characterized by increased movements and an The risk factors for agitation and delirium are many and overlap to a
apparent inability to get comfortable, or it can be severe. Severe agita- large extent (Table 2-1). Fortunately there are several mnemonics that
tion can be life threatening, leading to higher rates of self-extubation, can aid clinicians in recalling the list; two common ones are IWATCH-
self-removal of catheters and medical devices, nosocomial infections,4 DEATH and DELIRIUM (Table 2-2). In practical terms, risk factors
hypoxia, barotrauma, and/or hypotension due to patient/ventilator can be divided into three categories: the acute illness itself, patient
asynchrony. Indeed, recent studies have shown that agitation contrib- factors, and iatrogenic or environmental factors. Importantly, a number
utes to ventilator asynchrony, increased oxygen consumption, and of medications that are commonly used in the ICU are associated with
increased production of CO2 and lactic acid; these effects can lead to the development of agitation and delirium (Box 2-1). A thorough
life-threatening respiratory and metabolic acidosis.5 approach to the treatment and support of the acute illness (e.g., con-
trolling sources of sepsis and giving appropriate antibiotics; correcting
hypoxia, metabolic disturbances, dehydration, and hyperthermia; nor-
DELIRIUM malizing sleep/wake cycles), as well as minimizing iatrogenic factors
Delirium can be defined as follows: (1) A disturbance of consciousness (e.g., excessive sedation), can reduce the incidence and/or severity of
(i.e., reduced clarity of awareness of the environment) with reduced delirium and its attendant complications. A retrospective study con-
ability to focus, sustain, or shift attention. (2) A change in cognition ducted on postoperative delirium, specifically in patients undergoing
(e.g., memory deficit, disorientation, language disturbance) or develop- cardiopulmonary bypass, has alluded to a decreased incidence of delir-
ment of a perceptual disturbance that is not better accounted for by a ium in patients pre-treated with statins.31 Furthermore, ICU statins
preexisting, established, or evolving dementia. (3) The disturbance have been associated with decreased delirium, most significantly in the
develops over a short period (usually hours to days) and tends to fluctu- early stages of sepsis; in contrast to this, discontinuation of statins has
ate during the course of the day. (4) There is evidence from the history, been shown to be associated with increased delirium.32,33
physical examination, or laboratory findings that the disturbance is
a direct physiologic consequence of a general medical condition,
an intoxicating substance, medication use, or more than one cause
PATHOPHYSIOLOGY
(Fig. 2-1).3 Delirium is commonly underdiagnosed in the ICU and has The pathophysiology of delirium is poorly understood, although there
a reported prevalence of 20% to 80%, depending on the severity of are a number of hypotheses:
illness and the need for mechanical ventilation.7-10 Recent investigations • Neurotransmitter imbalance. Multiple neurotransmitters have
have shown that the presence of delirium is a strong predictor of longer been implicated, including dopamine (excess), acetylcholine (rela-
hospital stay, higher costs, and increased risk of death.11-13 Each addi- tive depletion), γ-aminobutyric acid (GABA), serotonin, endor-
tional day with delirium increases a patient’s risk of dying by 10%.14 phins, norepinephrine, and glutamate.34-37
Longer periods of delirium are also associated with greater degrees of • Inflammatory mediators. Inflammatory mediators, such as tumor
cognitive decline when patients are evaluated after one year.13 Thus, necrosis factor alpha (TNF-α), interleukin-1 (IL-1), and other cyto-
delirium can adversely affect the quality of life in survivors of critical kines and chemokines, have been implicated in the pathogenesis of
illnesses and may serve as an intermediate recognizable step for target- endothelial damage, thrombin formation, and microvascular dys-
ing therapies to prevent poor outcomes in survivors of critical illness.13,15 function in the central nervous system (CNS), contributing to
Unfortunately, the true prevalence and magnitude of delirium have delirium.37 Recently, a study in the ICU has strengthened the evi-
been poorly documented because myriad terms including acute confu- dence of a role for endothelial dysfunction in increasing the dura-
sional state, ICU psychosis, acute brain dysfunction, and encephalopathy, tion of delirium.38
6
CHAPTER 2 Agitation and Delirium 7
Mnemonic for Risk Factors for

TABLE 2-2
Delirium and Agitation
Arousable Unarousable
to voice to voice IWATCHDEATH DELIRIUM
Infection Drugs
Acute mental Fluctuating Withdrawal Electrolyte and physiologic abnormalities
status change mental status Acute metabolic Lack of drugs (withdrawal)
Trauma/pain Infection
Central nervous system pathology Reduced sensory input (blindness,
Delirium Coma deafness)
Inattention Disorganized Hypoxia Intracranial problems (CVA, meningitis,
thinking
seizure)
Deficiencies (vitamin B12, thiamine) Urinary retention and fecal impaction
Endocrinopathies (thyroid, adrenal) Myocardial problems (MI, arrhythmia,
Hallucinations, Altered level of CHF)
delusions, consciousness Acute vascular (hypertension,
illusions
shock)
Toxins/drugs
Heavy metals
CHF, congestive heart failure; CVA, cerebrovascular accident; MI, myocardial infarction.
FIGURE 2-1 ■ Acute brain dysfunction. Patients who are unresponsive

to voice are considered to be in a coma. Patients who respond to voice
can be further evaluated for delirium using validated delirium monitoring
Commonly Used Drugs Associated
instruments. Inattention is a cardinal feature of delirium. Other pivotal BOX 2-1
features include a change in mental status that fluctuates over hours
With Delirium and Agitation
to days, disorganized thinking, and altered levels of consciousness.
Benzodiazepines
While hallucinations, delusions, and illusions may be part of the percep-
Opiates (especially meperidine)
tual disturbances seen in delirium, they on their own are not synony- Anticholinergics
mous with delirium, a diagnosis of which requires the presence of Antihistamines
inattention and other pivotal features outlined above. (With permission H2 blockers
from E. Wesley Ely and A. Morandi) (www.icudelirium.org). Antibiotics
Corticosteroids
Metoclopramide
Risk Factors for Agitation

TABLE 2-1
and Delirium
Age >70 years BUN/creatinine ratio ≥18 dopamine, and norepinephrine in the CNS. Altered availability of
Transfer from a nursing home Renal failure, creatinine > 2.0 mg/dL these amino acids is associated with increased risk of development
History of depression Liver disease
of delirium.40
History of dementia, stroke, or epilepsy CHF
Alcohol abuse within past month Cardiogenic or septic shock ASSESSMENT
Tobacco use Myocardial infarction Recently, the Society of Critical Care Medicine (SCCM) published
Drug overdose or illicit drug use Infection guidelines for the use of sedatives and analgesics in the ICU.41 The
SCCM has recommended the routine monitoring of pain, anxiety, and
HIV infection CNS pathology
delirium and the documentation of responses to therapy for these
Psychoactive medications Urinary retention or fecal impaction conditions.42
Hypo- or hypernatremia Tube feeding There are many scales available for the assessment of agitation and
Hypo- or hyperglycemia Rectal or bladder catheters sedation, including the Ramsay Scale,43 the Riker Sedation-Agitation
Hypo- or hyperthyroidism Physical restraints Scale (SAS),44 the Motor Activity Assessment Scale (MAAS),45 the
Richmond Agitation-Sedation Scale (RASS),46 the Adaptation to Inten-
Hypothermia or fever Central line catheters
sive Care Environment (ATICE)47 scale, and the Minnesota Sedation
Hypertension Malnutrition or vitamin deficiencies Assessment Tool (MSAT).47 Most of these scales have good reliability
Hypoxia Procedural complications and validity among adult ICU patients and can be used to set targets
Acidosis or alkalosis Visual or hearing impairment for goal-directed sedative administration. The SAS, which scores agita-
Pain Sleep disruption tion and sedation using a 7-point system, has excellent inter-rater
reliability (kappa = 0.92) and is highly correlated (r2 = 0.83 to 0.86)
Fear and anxiety
with other scales. The RASS (Table 2-3), however, is the only method
BUN, blood urea nitrogen; CHF, congestive heart failure; CNS, central nervous system; HIV, shown to detect variations in the level of consciousness over time or
human immunodeficiency virus. in response to changes in sedative and analgesic drug use.48 The
10-point RASS scale has discrete criteria to distinguish levels of agita-
tion and sedation. The evaluation of patients consists of a 3-step
• Impaired oxidative metabolism. According to this hypothesis, process. First, the patient is observed to determine whether he or she
delirium is a result of cerebral insufficiency secondary to a global is alert, restless, or agitated (0 to +4). Second, if the patient is not alert
failure in oxidative metabolism.39 and does not show positive motoric characteristics, the patient’s name
• Large neutral amino acids. Increased cerebral uptake of trypto- is called and his or her sedation level scored based on the duration of
phan and tyrosine can lead to elevated levels of serotonin, eye contact (−1 to −3). Third, if there is no eye opening on verbal

TABLE 2-3 Richmond Agitation-Sedation Scale Feature 1: Acute onset of mental status changes
or a fluctuating course
+4 Combative Combative, violent, immediate
danger to staff And
+3 Very agitated Pulls or removes tube(s) or Feature 2: Inattention
catheter(s); aggressive
+2 Agitated Frequent nonpurposeful And
movement; fights ventilator
+1 Restless Anxious, apprehensive, but
movements not aggressive or Feature 3: Disorganized Feature 4: Altered level of
vigorous OR
thinking consciousness
0 Alert and calm
−1 Drowsy Not fully alert but has sustained
= Delirium
(>10 sec) awakening (eye
opening/contact) to voice
−2 Light sedation Drowsy; briefly (<10 sec) FIGURE 2-2 ■ Confusion Assessment Method in the Intensive Care
awakens to voice or physical Unit (CAM-ICU).
stimulation
−3 Moderate sedation Movement or eye opening (but
no eye contact) to voice
−4 Deep sedation No response to voice, but Intensive Care Delirium
TABLE 2-4
movement or eye opening to Screening Checklist
physical stimulation
−5 Unarousable No response to voice or physical PATIENT EVALUATION
stimulation Altered level of (A–E)*
consciousness
PROCEDURE FOR ASSESSMENT Inattention Difficulty in following a conversation or instructions.
1. Observe patient. Is patient alert, (Score 0 to +4) Easily distracted by external stimuli. Difficulty in
restless, or agitated? shifting focus. Any of these scores 1 point.
2. If not alert, state patient’s name and (Score −1) Disorientation Any obvious mistake in time, place, or person scores 1
tell him or her to open eyes and look point.
at speaker. Patient awakens, with Hallucinations- The unequivocal clinical manifestation of hallucination
sustained eye opening and eye contact. delusions- or behavior probably attributable to hallucination or
3. Patient awakens, with eye opening and (Score −2) psychosis delusion. Gross impairment in reality testing. Any of
eye contact, but not sustained. these scores 1 point.
4. Patient does not awaken (no eye (Score −3) Psychomotor agitation Hyperactivity requiring the use of additional sedative
contact) but has eye opening or or retardation drugs or restraints to control potential danger to self
movement in response to voice. or others. Hypoactivity or clinically noticeable
3. Physically stimulate patient by shaking (Score −4) psychomotor slowing.
shoulder and/or rubbing sternum. No Inappropriate speech Inappropriate, disorganized, or incoherent speech.
response to voice, but response or mood Inappropriate display of emotion related to events or
(movement) to physical stimulation. situation. Any of these scores 1 point.
4. No response to voice or physical (Score −5) Sleep/wake cycle Sleeping less than 4 h or waking frequently at night (do
stimulation disturbance not consider wakefulness initiated by medical staff
or loud environment). Sleeping during most of the
From Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation-Sedation Scale: validity
day. Any of these scores 1 point.
and reliability in adult intensive care unit patients. Am J Respir Crit Care Med
Symptom fluctuation Fluctuation of the manifestation of any item or
2002;166(10):1338-1344.
symptom over 24 h scores 1 point.
Total Score (0-8)
*Level of consciousness:
stimulation, the patient’s shoulder is shaken or pressure applied over A—No response: score 0.
the sternum by rubbing, and the response noted (−4 or −5). This assess- B—Response to intense and repeated stimulation (loud voice and pain): score 0.
ment takes less than 20 seconds in total and correlates well with other C—Response to mild or moderate stimulation: score 1.
measures of sedation (e.g., Glasgow Coma Scale [GCS], bispectral elec- D—Normal wakefulness: score 0.
troencephalography, and neuropsychiatric ratings).46 E—Exaggerated response to normal stimulation: score 1.
Available at: http://www.acgme.org/acgmeweb/tabid/445/GraduateMedicalEducation/
Until recently, there was no valid and reliable way to assess delirium
SingleAccreditationSystemforAOA-ApprovedPrograms.aspx. Accessed November 12.
in critically ill patients, many of whom are nonverbal owing to sedation
or mechanical ventilation.51,58 A number of tools have been developed
to aid in the detection of delirium in the ICU. These tools have been
validated for use in both intubated and nonintubated patients and To perform the CAM-ICU, patients are first evaluated for level of
measured against a “gold standard,” the Diagnostic and Statistical consciousness; patients who respond to verbal commands (a RASS
Manual of Mental Disorders (DSM) criteria. The tools are the Confu- score of −3 or higher level of arousal) can then be assessed for delirium.
sion Assessment Method for the ICU (CAM-ICU)51-55 and the Inten- The CAM-ICU comprises four features: (1) a change in mental status
sive Care Delirium Screening Checklist (ICDSC).8 from baseline or a fluctuation in mental status, (2) inattention, (3)
The CAM-ICU (Fig. 2-2) is a delirium measurement tool developed disorganized thinking, and (4) altered level of consciousness. Delirium
by a team of specialists in critical care, psychiatry, neurology, and is diagnosed if patients have features 1 and 2, and either feature 3 or 4
geriatrics.51,58 Administered by a nurse, the evaluation takes only 1 to is positive (see Fig. 2-2).
2 minutes to conduct and is 98% accurate in detecting delirium as The ICDSC8 (Table 2-4) is a checklist-based assessment tool
compared with a full DSM-V assessment by a geriatric psychiatrist.51,52 that evaluates inattention, disorientation, hallucination, delusion or

CHAPTER 2 Agitation and Delirium 9
psychosis, psychomotor agitation or retardation, inappropriate speech continued to have persistent delirium even after interruption of seda-
or mood, sleep/wake cycle disturbances, and fluctuations in these tion. Thus, when feasible, delirium evaluation should be performed
symptoms. Each of the eight items is scored as absent or present (0 or after interruption of sedation; however delirium evaluations should not
1), respectively, and summed. A score of 4 or above indicates delirium, be forgone just because a patient is under sedation since the omission
while 0 indicates no delirium. Patients with scores between 1 and 3 are of the diagnosis would be far worse than overdiagnosing delirium in a
considered to have subsyndromal delirium,59 which has worse prog- handful of patients.
nostic implications than the absence of delirium but a better prognosis
than clearly present delirium.
Recent studies have called into question the usefulness of delirium
MANAGEMENT
evaluations for patients under sedation.60,61 A small subset of patients The development of effective evidence-based strategies and proto-
(approximately 10%) were noted to have rapidly reversible sedation- cols for prevention and treatment of delirium awaits data from
related delirium, but unfortunately in this study the majority of patients ongoing randomized clinical trials of both nonpharmacologic and
Perform Delirium Assessment via CAM-ICU
Delirious (CAM-ICU positive)

Non-delirious Stupor or coma while on sedative
(CAM-ICU negative) or analgesic drugs7
Consider differential diagnosis (Dr. DRE or THINK) 1
(RASS –4 or –5)
Reassess CAM-ICU at least every

shift. Treat pain and anxiety if Remove deliriogenic drugs2
indicated via CPOT or RASS Non-pharmacological protocol3 Does the patient require deep sedation
or analgosedation?
RASS +2 to +4 RASS –1 to –3 Yes No
Is the patient in pain?4 Reassess target

RASS 0 to +1 sedation goal Perform SAT8
every shift
Yes No
Assure adequate pain control4
Consider typical or atypical If tolerates SAT, perform SBT9
Give analgesic5 antipsychotics6 Reassess target sedation goal
and perform SAT8
Give adequate sedative for safety

and titrate to goal RASS If tolerates SAT, perform SBT9
Consider typical or
atypical antipsychotics6
1. Dr. DRE: Non-pharmacological protocol3

Diseases: Sepsis, CHF, COPD
Drug Removal: SATs and stopping benzodiazepines/narcotics Orientation
Environment: Immobilization, sleep and day/night orientation, hearing aids, eye Provide visual and hearing aids
glasses, noise Encourage communication and reorient patient
THINK: repetitively. Have familiar objects from patient’s
Toxic Situations – CHF, shock, dehydration – Deliriogenic meds (tight titration) – home in the room
New organ failure (liver, kidney, etc.) Attempt consistency in nursing staff
Hypoxemia Family engagement and empowerment
Infection/sepsis (nosocomial), immobilization Environment
Nonpharmacological interventions3 Sleep hygiene: Lights off at night, on during day.
K+ or Electrolyte problems Control excess noise (staff, equipment), earplugs
2. Consider stoppinig or substituting deliriogenic medications such as benzodiazepines, Early mobilization and exercise
anticholinergic medications (metoclopramide, H2 blockers, promethazine, Music
diphenhydramine), steroids, etc. Clinical parameters
3. See non-pharmacological protocol – see below. Maintain systolic blood pressure > 90 mm Hg
4. If patient is non-verbal assess via CPOT, or if patient is verbal assess via visual analog Maintain oxygen saturations >90%
scale. Treat underlying metabolic derangements and infections
5. Analgesia – Adequate pain control may decrease delirium. Consider opiates, non-
steroidals, acetaminophen, or gabapentin (neuropathic pain).
6. Typical or atypical antipsychotics. Discontinue if high fever, QTc prolongation, or drug-
induced rigidity.
7. Consider non-benzodiazepine sedation strategies (propofol or dexmedetomidine)
8. Spontaneous Awakening Trial (SAT) – If meets safety criteria (no active seizures, no
alcohol withdrawal, no agitation, no paralytics, no myocardial ischemia, normal
intracranial pressure, FiO2 ≤ 70%)
9. Spontaneous Breathing Trial (SBT) – If meets safety criteria (no agitation, no myocardial
ischemia, FiO2 ≤ 50%, adequate inspiratory efforts, O2 saturation ≥ 88%, no vasopressor
use, PEEP ≤ 7.5 cm)
FIGURE 2-3 ■ Delirium Protocol as a part of ABCDEF Bundle.

pharmacologic strategies. Refer to Chapter 51 for a detailed description that dexmedetomidine can decrease the duration and prevalence of
of management strategies of delirium, including an empiric sedation delirium when compared to lorazepam or midazolam. Pharmacologic
and delirium protocol. A brief overview is provided here. therapy should be attempted only after correcting any contributing
When agitation or delirium develops in a previously comfortable factors or underlying physiologic abnormalities. Although these agents
patient, a search for the underlying cause should be undertaken before are intended to improve cognition, they all have psychoactive effects
attempting pharmacologic intervention. A rapid assessment should be that can further cloud the sensorium and promote a longer overall
performed, including assessment of vital signs and physical examina- duration of cognitive impairment. Patients who manifest delirium
tion to rule out life-threatening problems (e.g., hypoxia, self-extubation, should be treated with traditional antipsychotic medication. Newer
pneumothorax, hypotension), or other acutely reversible physiologic “atypical” antipsychotic agents (e.g., risperidone, ziprasidone, quetiap-
causes (e.g., hypoglycemia, metabolic acidosis, stroke, seizure, pain). ine, olanzapine) may decrease the duration of delirium.76
The previously mentioned IWATCHDEATH and DELIRIUM mne- Benzodiazepines are not recommended for the management of
monics can be particularly helpful in guiding this initial evaluation. delirium because they can paradoxically exacerbate delirium. These
Once life-threatening causes are ruled out as possible etiologies, drugs can also promote oversedation and respiratory suppression.
aspects of good patient care such as reorienting patients, improving However, they remain the drugs of choice for the treatment of delirium
sleep and hygiene, providing visual and hearing aids if previously used, tremens (and other withdrawal syndromes), and seizures.
removing medications that can provoke delirium, and decreasing the At times, mechanical restraints may be needed to ensure the safety
use of invasive devices if not required (e.g., bladder catheters, restraints), of patients and staff while waiting for medications to take effect. It is
should be undertaken. important to keep in mind, however, that restraints can increase agita-
The use of ABCDEs (Awakening and Breathing Trials, Choice tion and delirium, and their use may have adverse consequences,
of appropriate sedation, Delirium monitoring and management, including strangulation, nerve injury, skin breakdown, and other com-
and Early mobility and Exercise) has been shown to decrease the plications of immobilization.
incidence of delirium and improve patient outcome (Fig. 2-3). This
algorithm based on the PAD 2013 guidelines41 involves the following:
(1) Routine assessment of agitation, depth and quality of sedation and
SUMMARY
delirium using appropriate scales (RASS and SAS for agitation and Agitation and delirium are very common in the ICU, where their
sedation and CAM-ICU or ICDSC for delirium). They recommend occurrence puts patients at risk of self-injury and poor clinical out-
using protocol target-based sedation and targeting the lightest pos- comes. Available sedation and delirium monitoring instruments allow
sible sedation, thus exposing the patient to lower cumulative doses of clinicians to recognize these forms of brain dysfunction. Through a
sedatives62 and/or daily awakening trials63 and spontaneous breath- systematic approach, life-threatening problems and other acutely
ing trials64 to reduce the total time spent on mechanical ventilation. reversible physiologic causes can be rapidly identified and remedied.
Coordination of daily awakening and daily breathing was associated A strategy that focuses on early liberation from mechanical ventilation
with shorter durations of mechanical ventilation, reduction in length and early mobilization can help reduce the burden of delirium. Use of
of hospital stay, and no long-term neuropsychologic consequences of antipsychotics should be reserved for patients who pose an imminent
waking patients during critical illness.65,66 (2) Treatment should start risk to themselves or staff.
with treating analgesia first. Choosing the right sedative regimen in
critically ill patients is important. Numerous studies have confirmed
that benzodiazepines are associated with poor clinical outcomes.67,68,69 KEY POINTS
The guidelines also recommend avoiding rivastigmine and antipsy-
chotics if there is an increased risk of Torsades de Pointes. (3) Pre- 1. Delirium
vention also plays an important role. Exercise and early mobility in 2. Agitation
ICU patients is associated with decreased length of both ICU and
hospital polypharmacy.70,71 Risk factors for delirium need to be identi- 3. Confusion
fied and eliminated. Promoting sleep and restarting baseline antipsy- 4. Assessment
chotic medications are also important. Data from the Maximizing 5. Risk factors
Efficacy of Targeted Sedation and Reducing Neurological Dysfunction 6. Management
(MENDS)67 study and the Safety and Efficacy of Dexmedetomidine 7. Sedation
Compared to Midazolam (SEDCOM) trial69 also support the view
ANNOTATED REFERENCES
Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, et al. Delirium as a predictor of This cohort study demonstrated a dose-response curve between days of delirium and the risk of dying
mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291(14): at 1 year.
1753-1762. Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, et al. Delirium in mechanically ventilated
This large cohort study showed that delirium in the ICU was an independent risk factor for death at 6 patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-
months and that each day with delirium increased the hazards of dying by 10%. ICU). JAMA 2001;286(21):2703-2710.
Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive Care Delirium Screening Checklist: A landmark study validating for the first time an easy to use bedside delirium-monitoring instrument
evaluation of a new screening tool. Intensive Care Med 2001;27(5):859-864. (Available at: http://www for nonverbal mechanically ventilated patients. Delirium monitoring with the CAM-ICU can be
.acgme.org/acgmeweb/tabid/445/GraduateMedicalEducation/SingleAccreditationSystemforAOA- performed in less than 2 minutes and does not require a psychiatrist.
ApprovedPrograms.aspx. Accessed November 12.) Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, et al. Early physical and
The ICDSC provides health care providers with an easy to use bedside delirium monitoring instrument occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial.
that can be incorporated into the daily work flow of bedside nurses. It provides the ability to Lancet 2009;373(9678):1874-1882.
diagnose subsyndromal delirium. This is the only interventional study that tested a nonpharmacologic intervention—early mobility—in
Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van Ness PH. Days of delirium are associated with ICU patients, and showed a reduction in delirium and improvements in functional outcomes.
1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med 2009;
180(11):1092-1097.
References for this chapter can be found at expertconsult.com.

CHAPTER 2 Agitation and Delirium 10.e1
REFERENCES
1. Chevrolet JC, Jolliet P. Clinical review: agitation and delirium in the critically ill–significance and 37. Gunther ML, Morandi A, Ely EW. Pathophysiology of delirium in the intensive care unit. Crit Care
management. Crit Care 2007;11(3):214. Clin 2008;24(1):45-65.
2. Deleted in review. 38. Hughes CG, Morandi A, Girard TD, Riedel B, Thompson JL, Shintani AK, et al. Association between
3. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders endothelial dysfunction and acute brain dysfunction during critical illness. Anesthesiology. 2013;
(5th ed.). Arlington, VA: American Psychiatric Publishing. 118(3):631-639.
4. Jaber S, Chanques G, Altairac C, Sebbane M, Vergne C, Perrigault PF, et al. A prospective study of 39. Fink MP, Evans TW. Mechanisms of organ dysfunction in critical illness: report from a Round Table
agitation in a medical-surgical ICU: incidence, risk factors, and outcomes. Chest 2005;128(4): Conference held in Brussels. Intensive Care Med 2002;28(3):369-375.
2749-2757. 40. Pandharipande PP, Morandi A, Adams JR, Girard TD, Thompson JL, Shintani AK, et al. Plasma
5. Cohen I, Gallagher T, Pohlman A, Dasta J, Abraham E, Papadokos P. Management of the agitated tryptophan and tyrosine levels are independent risk factors for delirium in critically ill patients.
intensive care unit patient. Crit Care Med 2002;30(1):S97–S123. Intensive Care Med 2009;35(11):1886-1892.
6. Pandharipande P, Jackson J, Ely EW. Delirium: acute cognitive dysfunction in the critically ill. Curr 41. Barr J, Fraser GL, Puntillo K, Ely EW, Gelinas C, Dasta JF, et al. Clinical practice guidelines for
Opin Crit Care 2005;11(4):360-368. the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit
7. Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, et al. Delirium as a predictor of Care Med 2013;41(1):263-306.
mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291(14): 42. Pandharipande PP, Patel MB, Barr J. Management of pain, agitation, and delirium in critically ill
1753-1762. patients. Pol Arch Med Wewn 2014;124(3):114-123.
8. Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive Care Delirium Screening Checklist: 43. Ramsay MA. Measuring level of sedation in the intensive care unit. JAMA 2000;284(4):441-442.
evaluation of a new screening tool. Intensive Care Med 2001;27(5)859-864 (Available at:http://www 44. Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Sedation-Agitation Scale for adult
.acgme.org/acgmeweb/tabid/445/GraduateMedicalEducation/SingleAccreditationSystemforAOA- critically ill patients. Crit Care Med 1999;27(7):1325-1329.
ApprovedPrograms.aspx. Accessed November 12 , 2016). 45. Devlin JW, Boleski G, Mlynarek M, Nerenz DR, Peterson E, Jankowski M, et al. Motor Activity
9. McNicoll L, Pisani MA, Zhang Y, Ely EW, Siegel MD, Inouye SK. Delirium in the intensive care Assessment Scale: a valid and reliable sedation scale for use with mechanically ventilated patients in
unit: occurrence and clinical course in older patients. J Am Geriatr Soc 2003;51(5):591-598 (Available an adult surgical intensive care unit. Crit Care Med 1999;27(7):1271-1275.
at:http://www.acgme.org/acgmeweb/tabid/445/GraduateMedicalEducation/SingleAccreditation 46. Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, et al. Monitoring sedation
SystemforAOA-ApprovedPrograms.aspx. Accessed November 12 , 2016). status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale
10. Girard TD, Pandharipande PP, Ely EW. Delirium in the intensive care unit. Crit Care 2008;12(Suppl. (RASS). JAMA 2003;289(22):2983-2991.
3):S3. 47. Weinert C, McFarland L. The state of intubated ICU patients: development of a two-dimensional
11. Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T, et al. The impact of delirium in the sedation rating scale for critically ill adults. Chest 2004;126(6):1883-1890.
intensive care unit on hospital length of stay. Intensive Care Med 2001;27(12):1892-1900. 48. Sessler CN, Grap MJ, Ramsay MA. Evaluating and monitoring analgesia and sedation in the intensive
12. Milbrandt EB, Deppen S, Harrison PL, Shintani AK, Speroff T, Stiles RA, et al. Costs associated with care unit. Critical Care 2008;12(Suppl. 3):S2.
delirium in mechanically ventilated patients. Crit Care Med 2004;32(4):955-962. 49. Deleted in review.
13. Girard TD, Jackson JC, Pandharipande PP, Pun BT, Thompson JL, Shintani AK, et al. Delirium as a 50. Deleted in review.
predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med 2010; 51. Ely EW, Margolin R, Francis J, May L, Truman B, Dittus R, et al. Evaluation of delirium in critically
38(7):1513-1520. ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).
14. Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van Ness PH. Days of delirium are associated Crit Care Med 2001;29(7):1370-1379.
with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med 2009; 52. Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, et al. Delirium in mechanically venti-
180(11):1092-1097. lated patients: validity and reliability of the confusion assessment method for the intensive care unit
15. Jackson JC, Gordon SM, Hart RP, Hopkins RO, Ely EW. The association between delirium and cogni- (CAM-ICU). JAMA 2001;286(21):2703-2710.
tive decline: a review of the empirical literature. Neuropsychol Rev 2004;14(2):87-98. 53. Lin SM, Liu CY, Wang CH, Lin HC, Huang CD, Huang PY, et al. The impact of delirium on the
16. Morandi A, Pandharipande P, Trabucchi M, Rozzini R, Mistraletti G, Trompeo AC, et al. Understand- survival of mechanically ventilated patients. Crit Care Med 2004;32(11):2254-2259.
ing international differences in terminology for delirium and other types of acute brain dysfunction 54. Larsson C, Axell AG, Ersson A. Confusion assessment method for the intensive care unit (CAM-
in critically ill patients. Intensive Care Med 2008;34(10):1907-1915. ICU): translation, retranslation and validation into Swedish intensive care settings. Acta Anaesthesiol
17. Peterson JF, Truman BL, Shintani A, Thomason JWW, Jackson JC, Ely EW. The prevalence of hypoac- Scand 2007;51(7):888-892.
tive, hyperactive, and mixed type delirium in medical ICU patients. J Am Geriatr Soc 2003;51:S174. 55. McNicoll L, Pisani MA, Ely EW, Gifford D, Inouye SK. Detection of delirium in the intensive care
18. Peterson JF, Pun BT, Dittus RS, Thomason JW, Jackson JC, Shintani AK, et al. Delirium and its unit: comparison of confusion assessment method for the intensive care unit with confusion assess-
motoric subtypes: a study of 614 critically ill patients. J Am Geriatr Soc 2006;54(3):479-484. ment method ratings. J Am Geriatr Soc 2005;53(3):495-500.
19. Pandharipande P, Cotton BA, Shintani A, Thompson J, Costabile S, Truman Pun B, et al. Motoric 56. Deleted in review.
subtypes of delirium in mechanically ventilated surgical and trauma intensive care unit patients. 57. Deleted in review.
Intensive Care Med 2007;33(10):1726-1731. 58. Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the
20. Meagher DJ, O’Hanlon D, O’Mahony E, Casey PR, Trzepacz PT. Relationship between symptoms and confusion assessment method. A new method for detection of delirium. Ann Intern Med
motoric subtype of delirium. J Neuropsychiatry Clin Neurosci 2000;12(1):51-56. 1990;113(12):941-948.
21. Kiely D, Jones R, Bergmann M, Marcantonio E. Association between psychomotor activity delirium 59. Ouimet S, Riker R, Bergeon N, Cossette M, Kavanagh B, Skrobik Y. Subsyndromal delirium in the
subtypes and mortality among newly admitted postacute facility patients. J Gerontol A Biol Sci Med ICU: evidence for a disease spectrum. Intensive Care Med 2007;33(6):1007-1013.
Sci 2007;62(2):174. 60. Patel SB, Poston JT, Pohlman A, Hall JB, Kress JP. Rapidly reversible, sedation-related delirium
22. Meagher D, Adamis D, Leonard M, Trzepacz P, Grover S, Jabber F, et al. Development of an abbrevi- versus persistent delirium in the intensive care unit. Am J Respir Crit Care Med 2014;189(6):658–
ated version of the delirium motor subtyping scale (DMSS-4). Int Psychogeriatr 2014;26(04): 665.
693-702. 61. Haenggi M, Blum S, Brechbuehl R, Brunello A, Jakob SM, Takala J. Effect of sedation level on the
23. Ely EW, Stephens RK, Jackson JC, Thomason JW, Truman B, Gordon S, et al. Current opinions prevalence of delirium when assessed with CAM-ICU and ICDSC. Intensive Care Med 2013;
regarding the importance, diagnosis, and management of delirium in the intensive care unit: a survey 39(12):2171-2179.
of 912 healthcare professionals. Crit Care Med 2004;32(1):106-112. 62. Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D, Sherman G. The use of continuous i.v. sedation
24. Cheung CZ, Alibhai SM, Robinson M, Tomlinson G, Chittock D, Drover J, et al. Recognition and is associated with prolongation of mechanical ventilation. Chest 1998;114(2):541-548.
labeling of delirium symptoms by intensivists: does it matter? Intensive Care Med 2008;34(3): 63. Kress JP, Pohlman AS, O’Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill
437-446. patients undergoing mechanical ventilation. N Engl J Med. 2000;342(20):1471-1477.
25. Devlin JW, Fong JJ, Howard EP, Skrobik Y, McCoy N, Yasuda C, et al. Assessment of delirium in the 64. Ely EW, Baker AM, Dunagan DP, Burke HL, Smith AC, Kelly PT, et al. Effect on the duration of
intensive care unit: nursing practices and perceptions. Am J Crit Care 2008;17(6):555-565. mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med
26. Van Eijk MM, Kesecioglu J, Slooter AJ. Intensive care delirium monitoring and standardised 1996;335(25):1864-1869.
treatment: a complete survey of Dutch intensive care units. Intensive Crit Care Nurs 2008;24(4): 65. Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, et al. Efficacy and safety
218-221. of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive
27. Cadogan FL, Riekerk B, Vreeswijk R, Rommes JH, Toornvliet AC, Honing ML, et al. Current aware- care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 2008;
ness of delirium in the intensive care unit: a postal survey in the Netherlands. Neth J Med 2009; 371(9607):126-134.
67(7):296-300. 66. Jackson JC, Girard TD, Gordon SM, Thompson JL, Shintani AK, Thomason JW, et al. Long-term
28. Patel RP, Gambrell M, Speroff T, Scott TA, Pun BT, Okahashi J, et al. Delirium and sedation in the cognitive and psychological outcomes in the awakening and breathing controlled trial. Am J Respir
intensive care unit: survey of behaviors and attitudes of 1384 healthcare professionals. Crit Care Med Crit Care Med 2010;182(2):183-191.
2009;37(3):825-832. 67. Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, et al. Effect of sedation with
29. Salluh JI, Dal-Pizzol F, Mello PV, Friedman G, Silva E, Teles JM, et al. Delirium recognition and dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the
sedation practices in critically ill patients: a survey on the attitudes of 1015 Brazilian critical care MENDS randomized controlled trial. JAMA 2007;298(22):2644-2653.
physicians. J Crit Care 2009;24(4):556-562. 68. Pandharipande PP, Sanders RD, Girard TD, McGrane S, Thompson JL, Shintani AK, et al. Effect of
30. Mac Sweeney R, Barber V, Page V, Ely EW, Perkins GD, Young JD, et al. A national survey of the dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis
management of delirium in UK intensive care units. QJM 2010;103(4):243-251. of the MENDS randomized controlled trial. Crit Care 2010;14(2):R38.
31. Katznelson R, Djaiani GN, Borger MA, Friedman Z, Abbey SE, Fedorko L, et al. Preoperative use of 69. Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, et al. Dexmedetomidine
statins is associated with reduced early delirium rates after cardiac surgery. Anesthesiology 2009; vs midazolam for sedation of critically ill patients: a randomized trial. JAMA 2009;301(5):489–
110(1):67-73. 499.
32. Pandharipande P, Shintani A, Hughes C, et al. Statin use and the daily risk of delirium in a prospective 70. Morris PE, Goad A, Thompson C, Taylor K, Harry B, Passmore L, et al. Early intensive care
cohort of critically ill patients. Am J Respir Crit Care Med 2012;185:A3646. unit mobility therapy in the treatment of acute respiratory failure. Crit Care Med 2008;36(8):
33. Morandi A, Hughes CG, Thompson JL, Pandharipande PP, Shintani AK, Vasilevskis EE, et al. Statins 2238-2243.
and delirium during critical illness: a multicenter, prospective cohort study. Crit Care Med 71. Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, et al. Early physical
2014;42(8):1899-1909. and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled
34. Trzepacz PT. Update on the neuropathogenesis of delirium. Dement Geriatr Cogn Disord 1999; trial. Lancet 2009;373(9678):1874-1882.
10(5):330-334. 72. Deleted in review.
35. Trzepacz PT. Delirium. Advances in diagnosis, pathophysiology, and treatment. Psychiatr Clin North 73. Deleted in review.
Am 1996;19(3):429-448. 74. Deleted in review.
36. Flacker JM, Lipsitz LA. Large neutral amino acid changes and delirium in febrile elderly medical 75. Deleted in review.
patients. J Gerontol A Biol Sci Med Sci 2000;55(5):B249–B252 (Available at: http://www.acgme.org/ 76. Skrobik YK, Bergeron N, Dumont M, Gottfried SB. Olanzapine vs haloperidol: treating delirium in
acgmeweb/tabid/445/GraduateMedicalEducation/SingleAccreditationSystemforAOA-Approved a critical care setting. Intensive Care Med 2004;30(3):444-449.
Programs.aspx. Accessed November 12 , 2015).

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Transcriber’s Notes
The language used in this text is that of the sourcce

document; changes to the text are listed below.
Depending on the hard- and software and their
settings used to read this text not all elements
may display as intended; many images may be
enlarged by opening them in a new window or tab.
Page 32, ... an angle of about 2°: possibly an error
for ... an angle of about 20° (which is the angle in
the illustration).
Page 113, illustration top right (Food Bags): Fut and
Ergswurst may be errors for Fat and Erbswurst
(pea sausage).
Page 262, ... in Fig. 9, illustrating an article on
“Taborets and Small Tables for the Summer
Veranda,” page 155, July, 1916 ...: an article with
this title (presumably the one referred to) is
present in this book on page 269.
Changes made
Illustrations have been moved out of text
paragraphs.
Minor obvious typographical errors have been
corrected silently.
Text in a dotted box has been transcribed from the
accompanying illustration, and does not appear as
part of the text in the source document.
Some entries in the table of contents have been
corrected to conform to the spelling used in the
text.
In some of the illustrations feet or misprinted inch
symbols (′) have been changed to inch symbols (″)
when necessary.
On several pages the first letter of the main article
has been replaced with a large capital, as in
similar articles in the book.
Page 29: Fig 7 has been rotated 90°.
Page 89: ... directly from the canoe, or part, to be
fitted, whenever convenient ... changed to ...
directly from the canoe, or part to be fitted,
whenever convenient ....
Page 94: illustration Ice Creeper turned upside-
down.
Page 213: ... a wear and noise-proof bearing ...
changed to ... a wear- and noise-proof bearing ....
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JEAN-LOUIS VINCENT, MD, PhD PATRICK M. KOCHANEK, MD, MCCM

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TEXTBOOK OF CRITICAL CARE, SEVENTH EDITION ISBN: 978-0-323-37638-9

Copyright © 2017 by Elsevier Inc. All rights reserved.

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Textbook of Critical Care, Seventh Edition

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